| 1. |
- Grahn, Anna, 1973, et al.
(författare)
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Cerebrospinal fluid biomarkers in patients with varicella-zoster virus CNS infections.
- 2013
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 260:7, s. 1813-1821
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Tidskriftsartikel (refereegranskat)abstract
- Varicella-zoster virus (VZV) is one of our most common viruses causing central nervous system (CNS) infection with sometimes severe neurological complications. Glial fibrillary acidic protein (GFAp), light subunit of neurofilament protein (NFL) and S-100β protein are cerebrospinal fluid (CSF) biomarkers that have been used to estimate the severity of brain damage and outcome in various CNS diseases. So far, these biomarkers have not been utilised to investigate glial pathology and neuronal damage in patients with VZV CNS infections. In this prospective study, we measured CSF GFAp, NFL and S-100β as markers of brain damage in 24 patients with acute neurological manifestations and VZV DNA detected in CSF by PCR and compared with a control group (n=14). Concentrations of CSF NFL and GFAp were increased in patients with VZV CNS infection compared with controls (p=0.002 and p=0.03) while levels of S-100β were reduced. In patients with VZV encephalitis the elevations of CSF NFL and GFAp were more pronounced compared with patients with other VZV CNS syndromes. No correlations between the levels of biomarkers and viral load, neurological sequels or clinical outcome were found in this limited number of patients. These results indicate that VZV induces neuronal damage and astrogliosis with more severe brain damage in patients with VZV encephalitis than in patients with other neurological complications caused by this virus.
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| 2. |
- Grahn, Anna, 1973, et al.
(författare)
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Cognitive impairment 3 years after neurological Varicella-zoster virus infection: a long-term case control study
- 2013
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 260:11, s. 2761-2769
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Tidskriftsartikel (refereegranskat)abstract
- Varicella-zoster virus (VZV) is one of the most common viruses causing central nervous system (CNS) infection, sometimes with severe neurological complications and sequelae despite appropriate antiviral treatment. Whether the neurological sequelae of VZV CNS infections include long-term cognitive impairment and how this impairment might affect the patients is still largely unknown. In this study, 14 patients with predominant CNS manifestations caused by VZV infection underwent cognitive testing 3 years (median 39.5 months, range 31-52 months) after acute disease. The results were compared with those for 28 controls, matched for age and gender. The tests covered the cognitive domains of speed and attention, memory and learning, visuospatial function, language and executive function. To further assess the cognitive dysfunction caused by neurological VZV infection, patients were classified into the concept of mild cognitive impairment (MCI), which is associated with development of dementia in other pathologies. The VZV patients performed significantly worse than controls on four tests covering the domains of speed and attention, memory and learning and executive function. The cut-off was set at 1.5 SD below mean age. In addition, a greater proportion of VZV patients were classified with MCI as compared with controls. In conclusion, patients with previous VZV infection affecting the brain had signs of long-term cognitive impairment in the domains of speed and attention, memory and learning and executive function. However, larger study populations are needed to confirm these results.
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| 3. |
- Krut, Jan Jessen, et al.
(författare)
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Cerebrospinal fluid Alzheimer's biomarker profiles in CNS infections.
- 2013
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 230, s. 620-626
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Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) biomarker profile in Alzheimer's disease (AD) is characterized by decreased beta amyloid (Aβ(1-42)), increased total and hyperphosphorylated tau (t-tau and p-tau, respectively), which is a useful diagnostic tool and gives insight in the pathogenesis of AD. It is of importance to study how these biomarkers react in other CNS diseases; therefore, we decided to analyse amyloid and tau biomarkers in different CNS infections. We also included analysis of soluble amyloid precursor proteins (sAPPα and -β). CSF Aβ(1-42), sAPPα and -β, t-tau and p-tau were analysed in bacterial meningitis (n=12), Lyme neuroborreliosis (n=13), herpes simplex virus type 1 (HSV-1) encephalitis (n=10), HIV-associated dementia (HAD) (n=21), AD (n=21) and healthy controls (n=42). Concurrent with AD, Aβ(1-42) was decreased in all groups except neuroborreliosis compared to controls. HSV-1 encephalitis, bacterial meningitis and HAD showed lower concentrations of sAPPα and -β compared to AD. T-tau was increased in AD and HSV-1 encephalitis compared to all other groups. P-tau was higher in AD and HSV-1 encephalitis compared to bacterial meningitis, HAD and control. Decreased CSF Aβ(1-42), sAPPα and -β in various CNS infections imply an effect of neuroinflammation on amyloid metabolism which is similar in regard to AD concerning Aβ(1-42), but differs concerning sAPPα and -β. These results clearly indicate different pathologic pathways in AD and infectious CNS disease and may provide help in the differential biomarker diagnostics. Increased p-tau in HSV-1 encephalitis probably reflect acute neuronal damage and necrosis.
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| 4. |
- Sköldenberg, Birgit, et al.
(författare)
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Incidence and pathogenesis of clinical relapse after herpes simplex encephalitis in adults.
- 2006
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 253:2, s. 163-70
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To study the occurrence of relapse of herpes simplex encephalitis (HSE) and to find out whether soluble activity markers in cerebrospinal fluid (CSF) indicate direct viral or immune- mediated events. METHODS: A consecutive series of 32 adult survivors of HSE were followed to determine the incidence of clinical relapse of HSE. Four patients had neurological deterioration interpreted as relapsing HSE. Four non-relapsing HSE cases were selected as matched controls. Fifty nine batched, paired CSF and serum samples from the eight HSE patients were analysed for soluble activity markers, predominantly cytokines and mediators (interferon-gamma, soluble CD8, tumour necrosis factor-alpha, and interleukin-10), amount of HSV-DNA and markers of glial and neuronal destruction (neurofilament protein, glial fibrillary acidic protein, S-100-beta, and neuron specific enolase). RESULTS: Relapse of HSE was diagnosed in 3 of 26 (12 %) acyclovir-treated patients (5 episodes during 6.1 years of followup) and in 1 of 6 vidarabine-recipients. All relapses occurred from 1 to 4 months after acute HSE, except for a second relapse after 3.3 years in one patient. Computer tomography at relapses revealed few abnormalities apart from those found during the primary disease. Intravenous acyclovir and corticosteroids were given for 7-21 days in all the relapse patients. All relapse patients seemed to recover to the pre-relapse condition. HSV-DNA was demonstrated in CSF in all patients during the acute stage but not in any of 13 CSF samples taken during relapse phases. The HSV viral load during the acute stage of HSE was not higher or of longer duration in the relapsing patients than in the non-relapsing HSE controls. The levels of sCD8 were increased in nearly all CSF samples tested with peaks of sCD8 at one month of acute HSE. In all episodes of relapse, sCD8 peaks were detected during the first week at high levels. CSF levels of neuron-specific enolase, S-100 and glial fibrillary acidic protein were markedly lower at relapse than at the acute stage of HSV-1 encephalitis. CONCLUSION: The lack of demonstrable HSV DNA in CSF, the lack of acute CSF signs and the lack of signs of neural and glia cells destruction indicate that a direct viral cytotoxicity is not the major pathogenic mechanism in relapse. Instead, the pronounced CSF proinflammatory immunological response and the relative lack of CSF anti-inflammatory cytokine IL-10 response suggest immunologically-mediated pathogenicity.
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| 5. |
- Studahl, Marie, 1957, et al.
(författare)
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Difference in pathogenesis between herpes simplex virus type 1 encephalitis and tick-borne encephalitis demonstrated by means of cerebrospinal fluid markers of glial and neuronal destruction.
- 2000
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 247:8, s. 636-42
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Tidskriftsartikel (refereegranskat)abstract
- We determined the extent of neuronal and glial cell destruction in 13 patients with herpes simplex type 1 (HSV-1) encephalitis, 15 patients with tick-borne encephalitis (TBE), and 20 noninfectious controls by analyzing the cerebrospinal fluid (CSF) concentrations of neurofilament protein (a marker of neurons, mainly axons), neuron-specific enolase (a marker of neurons, mainly somas), glial fibrillary acidic protein, and S-100 protein (markers of astrocytes). In addition, in patients with HSV-1 encephalitis CSF samples were collected serially before 7, 8-14, and 18-49 days and 3-10 months after the onset of neurological symptoms. In the acute stage of HSV-1 encephalitis we found markedly higher CSF levels of the cell damage markers than in patients with TBE. The concentration of cell damage markers in HSV-1 encephalitis decreased within 45 days after acute infection, except for neurofilament protein. The CSF concentrations of neurofilament protein increased during the second week, remained extremely high throughout the next month, and decrease thereafter. The changes in these markers of neuronal and glial destruction demonstrate the neuronal and astroglial cell damage during the first month after HSV-1 encephalitis. In contrast, most patients with TBE had signs only of slight astrogliosis, except for two patients with paresis.
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