| 1. |
- Axelsson, M, et al.
(författare)
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Glial fibrillary acidic protein: a potential biomarker for progression in multiple sclerosis.
- 2011
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 1432-1459 .- 0340-5354. ; 258:5, s. 882-8
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Tidskriftsartikel (refereegranskat)abstract
- The major intermediate cytoskeletal protein of astrocytes, glial fibrillary acidic protein (GFAP), and that of axons, neurofilament light protein (NFL), may both be released into the cerebrospinal fluid (CSF) during pathological processes in the central nervous system (CNS). We investigated GFAP and NFL levels in CSF as possible biomarkers for progression in multiple sclerosis (MS). Patients with relapsing-remitting MS (RRMS, n = 15) or secondary progressive MS (SPMS, n = 10) and healthy control subjects (n = 28) were examined twice with an interval of 8-10 years apart. Neurological deficits were scored with the Expanded Disability Status Scale (EDSS). GFAP and NFL levels were determined in CSF by enzyme-linked immunosorbent assay (ELISA). GFAP levels and NFL levels correlated with age (r and r (s) = 0.50, p = 0.006). Adjusting for age, MS patients had increased GFAP levels compared with controls (p = 0.03) and GFAP levels correlated with neurological disability (EDSS, r = 0.51, p < 0.05) and disease progression [Multiple Sclerosis Severity Score (MSSS), r = 0.47, p < 0.05]. The mean annual increase of GFAP was 6.5 ng/L for controls, 8.1 ng/L for RRMS patients, and 18.9 ng/L for SPMS patients. GFAP level at the first examination had predictive value for neurological disability 8-10 years later (EDSS, r = 0.45, p < 0.05) but not for EDSS increase between the examinations. NFL levels were not significantly increased in MS patients compared with controls and had no relationship to disability or progression and no prognostic value for disability development. GFAP, a marker for astrogliosis, is a potential biomarker for MS progression and may have a role in clinical trials for assessing the impact of therapies on MS progression.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- Haghighi, Sara, et al.
(författare)
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Incidence of CSF abnormalities in siblings of multiple sclerosis patients and unrelated controls.
- 2000
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Ingår i: Journal of neurology. - 0340-5354 .- 1432-1459. ; 247:8, s. 616-22
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Tidskriftsartikel (refereegranskat)abstract
- We found that 19% (9/47) of healthy siblings of patients with clinically definite multiple sclerosis had an intrathecal immunological reaction with two or more 2 CSF-enriched oligoclonal bands (OCBs), in contrast to (4%) (2/50) unrelated healthy controls. Furthermore, in this group of nine healthy sibs the measles CSF IgG antibody titers were higher than that of the other sibs and that of controls. There were also differences in the serum titers for measles IgG antibody, which were higher in the group of all healthy sibs than in healthy volunteers, and (as with CSF titers) higher in the subgroup of healthy sibs with two or more 2 CSF-enriched OCBs than the other sibs. Thus a significant proportion of healthy siblings to MS patients have a partially hyperimmune condition similar to that occurring in MS, which in 19% manifested itself as an OCB reaction, in 9% as increased CSF measles IgG antibody titers, and in 21% as increased serum measles IgG antibody titers, these phenomena tending to occur in the same individuals. This condition is characterized by CSF-enriched OCBs with undefined specificity, although some increased antiviral reactivity is found both in the serum and CSF. While it needs further characterization, a genetic trait interacting with common infections is suggested. The recurrence risk of this condition is approximately five times higher than the 3-4% recurrence risk for manifest MS reported for sibs.
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| 5. |
- Pedersen, Annie, 1981, et al.
(författare)
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Circulating neurofilament light in ischemic stroke: temporal profile and outcome prediction
- 2019
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 266:11, s. 2796-2806
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Neurofilament light chain (NfL) is a marker of neuroaxonal damage. We aimed to study associations between serum NfL (sNfL) concentrations at different time points after ischemic stroke and outcomes. Methods We prospectively included ischemic stroke cases (n = 595, mean age 59 years, 64% males) and assessed outcomes by both the modified Rankin Scale (mRS) and the NIH stroke scale (NIHSS) at 3 months and by mRS at 2 years. In a subsample, long-term (7-year) outcomes were also assessed by both mRS and NIHSS. We used the ultrasensitive single-molecule array assay to measure sNfL in the acute phase (range 1–14, median 4 days), after 3 months and 7 years in cases and once in controls (n = 595). Results Acute-phase sNfL increased by the time to blood-draw and highest concentrations were observed at 3 months post-stroke. High sNfL associated to stroke severity and poor outcomes, and both associations were strongest for 3-month sNfL. After adjusting for age, previous stroke, stroke severity, and day of blood draw, 3-month sNfL was significantly associated to both outcomes at all time points (p < 0.01 throughout). For all main etiological subtypes, both acute phase and 3-month sNfL were significantly higher than in controls, but the dynamics of sNfL differed by stroke subtype. Conclusions The results from this study inform on sNfL in ischemic stroke and subtypes over time, and show that sNfL predicts short- and long-term neurological and functional outcomes. Our findings suggest a potential utility of sNfL in ischemic stroke outcome prediction.
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