| 1. |
- Andersen, Oluf, 1941, et al.
(författare)
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Diffusion tensor imaging in multiple sclerosis at different final outcomes
- 2018
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 137:2, s. 165-173
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:Methods to evaluate the relative contributions of demyelination vs axonal degeneration over the long-term course of MS are urgently needed. We used magnetic resonance diffusion tensor imaging (DTI) to estimate degrees of demyelination and axonal degeneration in the corpus callosum (CC) in cases of MS with different final outcomes.MATERIALS AND METHODS:We determined DTI measures mean diffusivity (MD), fractional anisotropy (FA), and axial (AD) and radial (RD) diffusivities in the CC of 31 MS patients, of whom 13 presented a secondary progressive course, 11 a non-progressive course, and seven a monophasic course. The study participants were survivors from an incidence cohort of 254 attack-onset MS patients with 50 years of longitudinal follow-up. As reference, we included five healthy individuals without significant morbidity.RESULTS:In patients with secondary progression, compared to all other groups, the corpus callosum showed increased RD and reduced FA, but no change in AD. None of the parameters exhibited differences among non-progressive and monophasic course groups and controls.CONCLUSION:Increased RD was observed in secondary progressive MS, indicating significant myelin loss. Normal RD values observed in the clinically isolated syndrome and non-progressive groups confirm their benign nature. AD was not a characterizing parameter for long-term outcome. Demyelination revealed by increased RD is a distinguishing trait for secondary progression.
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| 2. |
- Novakova, Lenka, et al.
(författare)
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Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Background Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. Objective This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course. Methods This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: Patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: Cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction. Results Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with progressive disease, but not with the other phenotypes. Thin retinal nerve fiber layers and low brain parenchymal fractions, which indicated neurodegeneration, were associated with longer disease duration. Conclusions In clinically suspected multiple sclerosis, intrathecal immunoglobin G production and neurofilament light chain levels had diagnostic value. Therefore, these biomarkers could be included in diagnostic work-ups for multiple sclerosis. We found that the thickness of the retinal nerve fiber layer and the brain parenchymal fraction were not different between individuals that were healthy, symptomatic, or newly diagnosed with multiple sclerosis. This finding suggested that neurodegeneration had not reached a significant magnitude in patients with a recent clinical onset of multiple sclerosis.
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| 3. |
- Novakova, Lenka, 1984, et al.
(författare)
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Sulfatide isoform pattern in cerebrospinal fluid discriminates progressive MS from relapsing-remitting MS
- 2018
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Ingår i: Journal of Neurochemistry. - : Wiley. - 0022-3042. ; 146:3, s. 322-332
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Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Several biomarkers including proteins and lipids have been reported in MS cerebrospinal fluid (CSF), reflecting different aspects of the pathophysiology particularly of relapsing-remitting MS (RRMS). Sulfatide, abundant in the myelin sheath and a proposed target for autoimmune attack in MS, has been reported altered in MS CSF. Here, we investigated the potential of CSF sulfatide and its isoforms as biomarkers in MS. A highly sensitive and quantitative mass spectrometry method was employed to determine levels of sulfatide isoforms in CSF from RRMS and progressive MS (PMS) patients, and healthy donors (HD). We demonstrate that levels of total CSF sulfatide and C24:1, C26:1, and C26:1-OH isoforms were significantly increased in PMS compared with RRMS patients and HD, while C23:0-OH was significantly decreased in CSF from PMS patients compared to the other two groups. Multivariate discriminant analysis showed that CSF sulfatide isoform pattern in PMS patients was distinct and non-overlapping with that of RRMS patients and HD. Sulfatide levels did not correlate with tested biomarkers or clinical parameters. The results suggest that CSF sulfatide isoform levels may be used to discriminate the phenotype ofMS and might play a role in the progression of the disease.
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| 4. |
- Nováková Nyrén, Lenka
(författare)
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Biomarkers in Multiple Sclerosis - Monitoring disease activity and treatment afficacy
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The pathophysiology of multiple sclerosis (MS) is complex with the presence of inflammation and neurodegeneration in all stages of the disease. The disease course, treatment response and outcome are highly variable in MS. There is a need for reliable biomarkers reflecting different parts of the pathophysiology of MS that may improve the decision-making between various treatment options. The aim of the thesis was to investigate the influence of different therapies on biomarker levels in cerebrospinal fluid (CSF) and blood, explore the relationships between inflammatory and degenerative biomarkers, their diagnostic value and the value of measuring brain atrophy, i.e. brain parenchymal fraction (BPF) and the thinning of retinal nerve fibre layer (RNFL) to detect signs of early degeneration. In study I, treatment with natalizumab reduced 24S-hydroxycholesterol concentrations in CSF and serum and 27-hydroxycholesterol concentrations in CSF. In study II, relapsing-remitting MS patients had higher levels of neurofilament light (NFL), CXCL13, chitinase-3-like-1 (CHI3L1), and chitotriosidase 1 (CHIT1) than controls. Subgroup analysis revealed higher levels of NFL, CXCL13 and CHIT1 in patients treated with first-line therapy compared to second-line therapy. NFL and CHIT1 levels correlated with relapse status, and NFL and CXCL13 levels correlated with the formation of new lesions on MRI. In study III, the levels of NFL, CXCL13, and CHI3L1 decreased after treatment with fingolimod. In study IV, high correlation between serum and CSF NFL was found. Serum concentrations of NFL were significantly higher in MS patients than in healthy controls and treatment reduced serum NFL levels. Patients with relapse or with radiologic activity had higher serum NFL levels than those in remission or those without new lesions on MRI. In study V, all phenotypes of MS had increased NFL compared to HC. Increased glial fibrillary acidic protein (GFAP), lower BPF and RNFL were associated with progressive MS but not with other phenotypes of MS. Lower BPF and RNFL, indicating neurodegeneration, were associated with longer disease duration. We showed that CSF biomarkers that represent different parts of the pathophysiology of MS were related to both clinical and radiological measures. The correlation between neurodegenerative and inflammatory biomarkers, and the lack of signs of neurodegeneration in the earliest phases of relapsing-remitting MS, confirms the hypothesis regarding inflammatory-induced degeneration. The most important finding is that the blood-based biomarker NFL can reflect the disease activity and treatment efficacy. This finding is based on a large set of paired serum and CSF samples from a real-life cohort of patients across a wide clinical and therapeutic spectrum. Therefore, repeated serum NFL measurements may represent new possibilities for the monitoring of MS.
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| 5. |
- Schriever, Valentin A., et al.
(författare)
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Development of an International Odor Identification Test for Children : The Universal Sniff Test
- 2018
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Ingår i: The Journal of Pediatrics. - : Elsevier BV. - 0022-3476 .- 1097-6833. ; 198, s. 265-272
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo assess olfactory function in children and to create and validate an odor identification test to diagnose olfactory dysfunction in children, which we called the Universal Sniff (U-Sniff) test.Study designThis is a multicenter study involving 19 countries. The U-Sniff test was developed in 3 phases including 1760 children age 5-7 years. Phase 1: identification of potentially recognizable odors; phase 2: selection of odorants for the odor identification test; and phase 3: evaluation of the test and acquisition of normative data. Test-retest reliability was evaluated in a subgroup of children (n = 27), and the test was validated using children with congenital anosmia (n = 14). Results Twelve odors were familiar to children and, therefore, included in the U-Sniff test. Children scored a mean +/- SD of 9.88 +/- 1.80 points out of 12. Normative data was obtained and reported for each country. The U-Sniff test demonstrated a high test-retest reliability (r(27) = 0.83, P < .001) and enabled discrimination between normosmia and children with congenital anosmia with a sensitivity of 100% and specificity of 86%.ConclusionsThe U-Sniff is a valid and reliable method of testing olfaction in children and can be used internationally.
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