Comparing molecular quantification of herpes simplex virus (HSV) in cerebrospinal fluid (CSF) with quantitative structural and functional disease severity in patients with HSV encephalitis (HSVE): Implications for improved therapeutic approaches

Kacy A. Ramirez, Asim Choudhri, Anami Patel, Noel T. Lenny, Rebecca E. Thompson, Leslie Berkelhammer Greenberg, Nancy Clanton Watson, Mehmet Kocak, John Devincenzo

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Herpes Simplex Virus encephalitis (HSVE) is a devastating disease of all ages. Rigorous studies correlating viral load with neuroradiological and clinical severity have not been performed, particularly in neonates. Understanding these relationships may improve therapies. Objectives: To correlate molecularly quantified HSV in cerebrospinal fluid (CSF) and disease severity. Study Design: HSV loads (VL) were evaluated by real-time PCR from the CSF of 33 patients (20 neonates, 5 children, 8 adults) with HSVE. We studied relationships between CSF VL and structural and volumetric brain abnormalities (MRI); hospital morbidity; and discharge and long-term (>3 month) clinical outcomes. Results: Initial CSF VL did not differ in neonates vs non-neonates (median 4.6 vs 5.1 log10 copies/mL, p = 0.75). Initial CSF VL was higher in neonates with HSV-2 vs HSV-1 (median 4.8 vs 3.2 log10 copies/mL, respectively, p = 0.02). Persistently detectable DNA in CSF despite acyclovir trended towards higher odds of unfavorable outcome at discharge for neonates [0.87 (CI 0.75–1), p = 0.07]. Initial VL correlated with higher CSF protein concentrations for the cohort and for neonates (p = 0.03 and 0.01, respectively), but not with lesion volume or subarachnoid exposure of involved brain (p all >0.05), hospital morbidity (p all >0.05), nor with higher odds of unfavorable discharge or long-term outcomes for the cohort [OR = 0.9(CI 0.5–1.6), p = 0.72; OR = 1.0(CI 0.5–1.8), p = 0.9] or for neonates [OR = 1.3(CI 0.5–3.3), p = 0.57; OR = 2.3(CI 0.7–8), p = 0.2]. Conclusions: Initial HSV VL did not predict neuroradiological or clinical outcomes in patients with HSVE, suggesting host inflammatory factors contribute to disease in treated patients with good viral clearance.

Original languageEnglish (US)
Pages (from-to)29-37
Number of pages9
JournalJournal of Clinical Virology
Volume107
DOIs
StatePublished - Oct 1 2018

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Herpes Simplex Encephalitis
Simplexvirus
Cerebrospinal Fluid
Newborn Infant
Encephalitis
Therapeutics
Morbidity
Cerebrospinal Fluid Proteins
Human Herpesvirus 2
Acyclovir
Brain
Human Herpesvirus 1
Viral Load
Real-Time Polymerase Chain Reaction
DNA

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

Cite this

Comparing molecular quantification of herpes simplex virus (HSV) in cerebrospinal fluid (CSF) with quantitative structural and functional disease severity in patients with HSV encephalitis (HSVE) : Implications for improved therapeutic approaches. / Ramirez, Kacy A.; Choudhri, Asim; Patel, Anami; Lenny, Noel T.; Thompson, Rebecca E.; Berkelhammer Greenberg, Leslie; Clanton Watson, Nancy; Kocak, Mehmet; Devincenzo, John.

In: Journal of Clinical Virology, Vol. 107, 01.10.2018, p. 29-37.

Research output: Contribution to journalArticle

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title = "Comparing molecular quantification of herpes simplex virus (HSV) in cerebrospinal fluid (CSF) with quantitative structural and functional disease severity in patients with HSV encephalitis (HSVE): Implications for improved therapeutic approaches",
abstract = "Background: Herpes Simplex Virus encephalitis (HSVE) is a devastating disease of all ages. Rigorous studies correlating viral load with neuroradiological and clinical severity have not been performed, particularly in neonates. Understanding these relationships may improve therapies. Objectives: To correlate molecularly quantified HSV in cerebrospinal fluid (CSF) and disease severity. Study Design: HSV loads (VL) were evaluated by real-time PCR from the CSF of 33 patients (20 neonates, 5 children, 8 adults) with HSVE. We studied relationships between CSF VL and structural and volumetric brain abnormalities (MRI); hospital morbidity; and discharge and long-term (>3 month) clinical outcomes. Results: Initial CSF VL did not differ in neonates vs non-neonates (median 4.6 vs 5.1 log10 copies/mL, p = 0.75). Initial CSF VL was higher in neonates with HSV-2 vs HSV-1 (median 4.8 vs 3.2 log10 copies/mL, respectively, p = 0.02). Persistently detectable DNA in CSF despite acyclovir trended towards higher odds of unfavorable outcome at discharge for neonates [0.87 (CI 0.75–1), p = 0.07]. Initial VL correlated with higher CSF protein concentrations for the cohort and for neonates (p = 0.03 and 0.01, respectively), but not with lesion volume or subarachnoid exposure of involved brain (p all >0.05), hospital morbidity (p all >0.05), nor with higher odds of unfavorable discharge or long-term outcomes for the cohort [OR = 0.9(CI 0.5–1.6), p = 0.72; OR = 1.0(CI 0.5–1.8), p = 0.9] or for neonates [OR = 1.3(CI 0.5–3.3), p = 0.57; OR = 2.3(CI 0.7–8), p = 0.2]. Conclusions: Initial HSV VL did not predict neuroradiological or clinical outcomes in patients with HSVE, suggesting host inflammatory factors contribute to disease in treated patients with good viral clearance.",
author = "Ramirez, {Kacy A.} and Asim Choudhri and Anami Patel and Lenny, {Noel T.} and Thompson, {Rebecca E.} and {Berkelhammer Greenberg}, Leslie and {Clanton Watson}, Nancy and Mehmet Kocak and John Devincenzo",
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T1 - Comparing molecular quantification of herpes simplex virus (HSV) in cerebrospinal fluid (CSF) with quantitative structural and functional disease severity in patients with HSV encephalitis (HSVE)

T2 - Implications for improved therapeutic approaches

AU - Ramirez, Kacy A.

AU - Choudhri, Asim

AU - Patel, Anami

AU - Lenny, Noel T.

AU - Thompson, Rebecca E.

AU - Berkelhammer Greenberg, Leslie

AU - Clanton Watson, Nancy

AU - Kocak, Mehmet

AU - Devincenzo, John

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Background: Herpes Simplex Virus encephalitis (HSVE) is a devastating disease of all ages. Rigorous studies correlating viral load with neuroradiological and clinical severity have not been performed, particularly in neonates. Understanding these relationships may improve therapies. Objectives: To correlate molecularly quantified HSV in cerebrospinal fluid (CSF) and disease severity. Study Design: HSV loads (VL) were evaluated by real-time PCR from the CSF of 33 patients (20 neonates, 5 children, 8 adults) with HSVE. We studied relationships between CSF VL and structural and volumetric brain abnormalities (MRI); hospital morbidity; and discharge and long-term (>3 month) clinical outcomes. Results: Initial CSF VL did not differ in neonates vs non-neonates (median 4.6 vs 5.1 log10 copies/mL, p = 0.75). Initial CSF VL was higher in neonates with HSV-2 vs HSV-1 (median 4.8 vs 3.2 log10 copies/mL, respectively, p = 0.02). Persistently detectable DNA in CSF despite acyclovir trended towards higher odds of unfavorable outcome at discharge for neonates [0.87 (CI 0.75–1), p = 0.07]. Initial VL correlated with higher CSF protein concentrations for the cohort and for neonates (p = 0.03 and 0.01, respectively), but not with lesion volume or subarachnoid exposure of involved brain (p all >0.05), hospital morbidity (p all >0.05), nor with higher odds of unfavorable discharge or long-term outcomes for the cohort [OR = 0.9(CI 0.5–1.6), p = 0.72; OR = 1.0(CI 0.5–1.8), p = 0.9] or for neonates [OR = 1.3(CI 0.5–3.3), p = 0.57; OR = 2.3(CI 0.7–8), p = 0.2]. Conclusions: Initial HSV VL did not predict neuroradiological or clinical outcomes in patients with HSVE, suggesting host inflammatory factors contribute to disease in treated patients with good viral clearance.

AB - Background: Herpes Simplex Virus encephalitis (HSVE) is a devastating disease of all ages. Rigorous studies correlating viral load with neuroradiological and clinical severity have not been performed, particularly in neonates. Understanding these relationships may improve therapies. Objectives: To correlate molecularly quantified HSV in cerebrospinal fluid (CSF) and disease severity. Study Design: HSV loads (VL) were evaluated by real-time PCR from the CSF of 33 patients (20 neonates, 5 children, 8 adults) with HSVE. We studied relationships between CSF VL and structural and volumetric brain abnormalities (MRI); hospital morbidity; and discharge and long-term (>3 month) clinical outcomes. Results: Initial CSF VL did not differ in neonates vs non-neonates (median 4.6 vs 5.1 log10 copies/mL, p = 0.75). Initial CSF VL was higher in neonates with HSV-2 vs HSV-1 (median 4.8 vs 3.2 log10 copies/mL, respectively, p = 0.02). Persistently detectable DNA in CSF despite acyclovir trended towards higher odds of unfavorable outcome at discharge for neonates [0.87 (CI 0.75–1), p = 0.07]. Initial VL correlated with higher CSF protein concentrations for the cohort and for neonates (p = 0.03 and 0.01, respectively), but not with lesion volume or subarachnoid exposure of involved brain (p all >0.05), hospital morbidity (p all >0.05), nor with higher odds of unfavorable discharge or long-term outcomes for the cohort [OR = 0.9(CI 0.5–1.6), p = 0.72; OR = 1.0(CI 0.5–1.8), p = 0.9] or for neonates [OR = 1.3(CI 0.5–3.3), p = 0.57; OR = 2.3(CI 0.7–8), p = 0.2]. Conclusions: Initial HSV VL did not predict neuroradiological or clinical outcomes in patients with HSVE, suggesting host inflammatory factors contribute to disease in treated patients with good viral clearance.

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