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- Novakova, Lenka, 1984, et al.
(författare)
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Reduced cerebrospinal fluid concentrations of oxysterols in response to natalizumab treatment of relapsing remitting multiple sclerosis.
- 2015
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 358:1-2, s. 201-206
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Tidskriftsartikel (refereegranskat)abstract
- Abstract BACKGROUND: Natalizumab therapy reduces inflammation and degeneration of the CNS in relapsing-remitting multiple sclerosis (RRMS). In cerebrospinal fluid (CSF) the concentration of 24S-hydroxycholesterol (24OHC) reflect neurodegeneration, whereas 27-hydroxycholesterol (27OHC) is dependent on the integrity of the blood-brain barrier (BBB). OBJECTIVE: To measure the impact from natalizumab treatment on 24OHC and 27OHC concentrations in serum and CSF of RRMS. METHODS: In serum and CSF obtained from 31 patients before and following 12 months of natalizumab treatment, 24OHC and 27OHC were analyzed by isotope-dilution mass spectrometry. RESULTS: Natalizumab treatment reduced CSF-24OHC concentrations (p=0.002), CSF-27OHC concentrations (p=0.01) and serum-24OHC concentrations (p=0.029). There was no significant effect of the treatment on serum-27OHC concentrations. Serum concentrations of 24OHC correlated with Symbol Digit Modalities Test scores before (r=0.5, p=0.007) and after natalizumab treatment (r=0.403, p=0.033). CONCLUSIONS: We showed for the first time that natalizumab treatment of RRMS reduced the concentrations of 24- and 27OHC in CSF, indicating reduced neurodegeneration and improved integrity of the BBB, respectively. Our results imply a role for serum 24OHC as a biomarker of cognition (visuo-spatial ability and processing speed) in RRMS.
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- Punga, Anna Rostedt, et al.
(författare)
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Disease specific signature of circulating miR-150-5p and miR-21-5p in myasthenia gravis patients
- 2015
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 356:1-2, s. 90-96
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Reliable biological markers for patients with the autoimmune neuromuscular disorder myasthenia gravis (MG) are lacking. We determined whether levels of the circulating immuno-microRNAs miR-150-5p and miR-21-5p were elevated in sera from clinically heterogeneous MG patients, with and without immunosuppression, as compared to healthy controls and patients with other autoimmune disorders. Methods: Sera from 71 MG patients and 55 healthy controls (HC) were analyzed for the expression levels of miR-150-5p and miR-21-5p with qRT-PCR. Sera were also assayed from 23 patients with other autoimmune disorders (AID; psoriasis, Addison's and Crohn's diseases). Results: 34 MG patients had no immunosuppressive drug treatment (MG-0) and 37 patients were under stable immunosuppressive drug treatment since a 6 months (MG + IMM). Serum levels of miR-150-5p and miR-21-5p were higher in the MG-0 patients compared to HC (p < 0.0001). Further, miR-150-5p levels were 41% lower and miR-21-5p levels were 25% lower in the MG + IMM compared to MG-0 (p = 0.0051 and 0.0419). In the AID patients, mean miR-150-5p and miR-21-5p were comparable with healthy controls (p = 0.66). Conclusions: The immuno-microRNAs miR-150-5p and miR-21-5p show a disease specific signature, which suggests these microRNAs as possible biological autoimmune markers of MG. (C) 2015 The Authors. Published by Elsevier B.V.
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- Sundgren, Mathias, et al.
(författare)
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Event related potential and response time give evidence for a physiological reserve in cognitive functioning in relapsing-remitting multiple sclerosis
- 2015
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Ingår i: Journal of the Neurological Sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 356:1-2, s. 107-112
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Tidskriftsartikel (refereegranskat)abstract
- Cognitive dysfunction is common in multiple sclerosis (MS). Different factors may moderate the degree of cognitive deficit. The aim of the present study was to distinguish different mechanisms for cognitive reserve in relapsing–remitting MS (RRMS). The effects of clinical variables (physical disability, depression), premorbid intelligence (years of education, vocabulary knowledge), visual event-related potentialmeasures (P300) and response time(RT)were studied in RRMS patients (n=71) and healthy subjects (n=89). Patients with high P300 amplitude and short RT had better cognitive performance. This effect was significantly weaker in controls. High P300 and short RT may be physiological markers of a cognitive reserve in RRMS. In contrast, the association between cognitive scores and premorbid intelligence was similar in patients and in control subjects. The effects of physiological reserve and clinical variables were studied in a hierarchical linear regression model of cognitive performance in RRMS. P300 amplitude and RT explained a considerable amount of variance in global cognitive performance (34%, p b 0.001). The effects of P300 and RTwere notmoderated by premorbid intelligence. Physical disability and depression added significantly to explained variance, and the final model accounted for 44% (p b 0.001) of the variation. We conclude that physiological reserve is the strongest moderator of cognitive impairment in RRMS
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