Prognostic value of intrathecal antibody production and DNA viral load in cerebrospinal fluid of patients with herpes simplex encephalitis

Hjalmarsson, Anders; Granath, Fredrik; Forsgren, Marianne; Brytting, Maria; Blomqvist, Peter; Sköldenberg, Birgit

doi:10.1007/s00415-009-5106-6

Cited by 20 publications

(17 citation statements)

References 24 publications

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“…This hypothesis is consistent with the fact that IgG levels were described to be significantly higher in patients with good prognostic than in patients with poor outcome [19]. …”

Section: Resultssupporting

confidence: 89%

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Impact of Herpes simplex virus load and red blood cells in cerebrospinal fluid upon herpes simplex meningo-encephalitis outcome

et al. 2012

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BackgroundHerpes simplex encephalitis (HSE) often leads to severe disability or death. Factors usually associated with outcome include Simplified Acute Physiology Score, age and delay of initiation of acyclovir treatment.Our aim was to determine the impact of Herpes simplex virus (HSV) load in cerebrospinal fluid (CSF) upon HSE outcome.MethodsWe retrospectively determined HSV load in the CSF of 43 patients with confirmed HSE, hospitalized in northern France from 1998 to 2005, using CSF samples collected the day of hospital admission and stored at −20°C. We analyzed the association between HSV load and mortality/morbidity by the Glasgow Outcome Scale. Fisher’s exact test and Wilcoxon’s test were used for statistical analysis.ResultsThe M/F sex ratio was 1.7 and median patient age was 61 years. Median HSV load in CSF was 2.0 log copies/μL (IQR 25-75=1.2-2.6). The mortality rate was 32.6% six months after HSE diagnosis. Higher age was associated with mortality (p=0.03). Longer delay in acyclovir initiation tended to be associated with higher mortality but did not reach statistical significance (p=0.08). Severe disability and death due to HSV were associated with a higher Knaus score (p=0.004), later acyclovir initiation (p=0.006), older age (p=0.04) and presence of red blood cells in CSF (p=0.05). HSV load in CSF was neither associated with mortality (p=1.00) nor with morbidity (p=0.90).ConclusionIn this study, HSV load in CSF was not found to be associated with poor outcome in patients with HSE. These data do not support measurement of HSV load at admission in patients with HSE.

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“…This hypothesis is consistent with the fact that IgG levels were described to be significantly higher in patients with good prognostic than in patients with poor outcome [19]. …”

Section: Resultssupporting

confidence: 89%

“…Our results are in agreement with Wildeman et al [10], Ruzek et al [11] and Hjalmarsson A et al . [19]. Kamei S et al ., who evaluated serial changes of intrathecal viral loads by chemiluminescence assay and nested PCR, did not find any evident association between viral load and outcome either [20].…”

Section: Resultsmentioning

confidence: 99%

Impact of Herpes simplex virus load and red blood cells in cerebrospinal fluid upon herpes simplex meningo-encephalitis outcome

et al. 2012

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“…Recurrent herpetic disease results from reactivation of HSV-1 from latency in sensory neurons and axonal transport to the periphery. Even though Herpes simplex virus (HSV) is a neurotropic virus, Herpes simplex encephalitis (HSE) occurs in only 2–3 previously healthy individuals/million/year in all age groups [1]. In more than ninety percent of the cases HSE is caused by HSV type1 and in the remaining by HSV type 2 [2].…”

Section: Introductionmentioning

confidence: 99%

Influence of Perineurial Cells and Toll-Like Receptors 2 and 9 on Herpes simplex Type 1 Entry to the Central Nervous System in Rat Encephalitis

et al. 2010

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Herpes simplex encephalitis (HSE) is a rare disease with high mortality and significant morbidity among survivors. We have previously shown that susceptibility to HSE was host-strain dependent, as severe, lethal HSE developed after injection of human Herpes simplex type 1 virus (HSV-1) into the whiskers area of DA rats, whereas PVG rats remained completely asymptomatic. In the present study we investigated the early immunokinetics in these strains to address the underlying molecular mechanisms for the observed difference. The virus distribution and the immunological responses were compared in the whiskers area, trigeminal ganglia and brain stem after 12 hours and the first four days following infection using immunohistochemistry and qRT-PCR. A conspicuous immunopathological finding was a strain-dependent difference in the spread of the HSV-1 virus to the trigeminal ganglia, only seen in DA rats already from 12 hpi. In the whiskers area infected perineurial cells were abundant in the susceptible DA strain after 2 dpi, whereas in the resistant PVG rats HSV-1 spread was confined only to the epineurium. In both strains activation of Iba1+/ED1+ phagocytic cells followed the distribution pattern of HSV-1 staining, which was visible already at 12 hours after infection. Notably, in PVG rats higher mRNA expression of Toll-like receptors (Tlr) -2 and -9, together with increased staining for Iba1/ED1 was detected in the whiskers area. In contrast, all other Tlr-pathway markers were expressed at higher levels in the susceptible DA rats. Our data demonstrate the novel observation that genetically encoded properties of the host nerve and perineurial cells, recruitment of phagocyting cells together with the low expression of Tlr2 and -9 in the periphery define the susceptibility to HSV-1 entry into the nervous system.

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“…The relation between the results of PCR and intrathecal antibody levels remains poorly understood. This issue has been addressed by one study but real-time PCR and measurement of antibody titers were performed in many patients at different times [4]. Intrathecal viral genomes on PCR and increased intrathecal HSV antibodies have been detected within five days [5] and after seven days [6] from the onset of neurologic symptoms, respectively.…”

Section: Discussionmentioning

confidence: 99%

A successfully treated case of herpes simplex encephalitis complicated by subarachnoid bleeding: a case report

et al. 2010

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IntroductionHistopathologically, herpes simplex virus type 1 causes hemorrhagic necrosis. Overt hemorrhage is infrequent in herpes simplex virus encephalitis but can lead to poor outcomes. This report describes a successfully treated case of herpes simplex virus encephalitis associated with subarachnoid bleeding in which real-time polymerase chain reaction was useful for diagnosis.Case presentationA 30-year-old previously healthy Japanese woman who had fever and headache for five days presented with disorganised speech, unusual behavior and delusional thinking. Real-time polymerase chain reaction amplification of herpes simplex virus type 1 in cerebrospinal fluid was positive (38,000 copies/mL) and antivirus treatment was started. During the course of her illness, the level of her consciousness decreased in association with desaturation and tachycardia. Thrombosis of the right pulmonary artery trunk with pulmonary embolism was evident on enhanced chest computed tomography. In addition, cranial computed tomography revealed subarachnoid and intraventricular bleeding. Intravenous heparin (12,000 U/day) was started and the dose was adjusted according to the activated partial thromboplastin time for about a month (maximum dose of heparin, 20,400 U/day). After the treatments, her Glasgow coma score increased and the thrombosis of the pulmonary artery trunk had disappeared.ConclusionsThe present case raises the question of whether anticoagulant treatment is safe in patients with herpes simplex virus encephalitis complicated by subarachnoid bleeding.

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Prognostic value of intrathecal antibody production and DNA viral load in cerebrospinal fluid of patients with herpes simplex encephalitis

Cited by 20 publications

References 24 publications

Impact of Herpes simplex virus load and red blood cells in cerebrospinal fluid upon herpes simplex meningo-encephalitis outcome

Impact of Herpes simplex virus load and red blood cells in cerebrospinal fluid upon herpes simplex meningo-encephalitis outcome

Influence of Perineurial Cells and Toll-Like Receptors 2 and 9 on Herpes simplex Type 1 Entry to the Central Nervous System in Rat Encephalitis

A successfully treated case of herpes simplex encephalitis complicated by subarachnoid bleeding: a case report

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