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- Svenningsson, Anders, et al.
(författare)
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Rapid depletion of B lymphocytes by ultra-low-dose rituximab delivered intrathecally
- 2015
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 2332-7812. ; 2:2
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We are conducting an open-label phase 1b study on the efficacy of intrathecal (IT) administration of rituximab, provided via an Ommaya reservoir, for the treatment of progressive multiple sclerosis (PMS). The objective of this initial study was to monitor B lymphocytes in peripheral blood (PB) and CSF from the first 10 patients 1 year posttreatment.Methods: Dose titration was performed with daily escalation from 1 mg to 25 mg IT rituximab (n=3). Lymphocyte subpopulations were monitored daily during dose escalation in PB by flow cytometry and subsequently every 3 months for 1 year, after a total dose of 3 x 25 mg. PB B-lymphocyte subpopulations for the remaining patients (n = 7) were monitored at regular intervals. CSF lymphocyte subpopulations for all patients were monitored by flow cytometry every 2-3 months.Results: The PB B-lymphocyte count dropped rapidly after the first 2 injections (total dose of 3.5 mg IT rituximab) to undetectable levels. Three 25-mg doses given once per week depleted peripheral B lymphocytes entirely for the following 3-6 month period.Conclusions: Monoclonal antibodies seem to rapidly redistribute to the peripheral compartment following IT injection. Ultra-low doses of rituximab given IT are sufficient to cause complete depletion of peripheral B lymphocytes, indicating that low-dose IT treatment has the potential to be effective in both the CNS and systemic compartments.Classification of evidence: This study provides Class IV evidence that for patients with PMS, rituximab provided via an Ommaya reservoir depletes peripheral blood B lymphocytes.
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| 2. |
- Vågberg, Mattias, et al.
(författare)
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Automated Determination of Brain Parenchymal Fraction in Multiple Sclerosis
- 2013
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Ingår i: American Journal of Neuroradiology. - : American Society of Neuroradiology. - 0195-6108 .- 1936-959X. ; 34:3, s. 498-504
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Brain atrophy is a manifestation of tissue damage in MS. Reduction in brain parenchymal fraction is an accepted marker of brain atrophy. In this study, the approach of synthetic tissue mapping was applied, in which brain parenchymal fraction was automatically calculated based on absolute quantification of the tissue relaxation rates R1 and R2 and the proton attenuation. MATERIALS AND METHODS: The BPF values of 99 patients with MS and 35 control subjects were determined by using SyMap and tested in relationship to clinical variables. A subset of 5 patients with MS and 5 control subjects were also analyzed with a manual segmentation technique as a reference. Reproducibility of SyMap was assessed in a separate group of 6 healthy subjects, each scanned 6 consecutive times. RESULTS: Patients with MS had significantly lower BPF (0.852 0.0041, mean +/- SE) compared with control subjects (0.890 +/- 0.0040). Significant linear relationships between BPF and age, disease duration, and Expanded Disability Status Scale scores were observed (P less than .001). A strong correlation existed between SyMap and the reference method (r = 0.96; P less than .001) with no significant difference in mean BPF. Coefficient of variation of repeated SyMap BPF measurements was 0.45%. Scan time was less than6 minutes, and postprocessing time was less than2 minutes. CONCLUSIONS: SyMap is a valid and reproducible method for determining BPF in MS within a clinically acceptable scan time and postprocessing time. Results are highly congruent with those described using other methods and show high agreement with the manual reference method.
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| 4. |
- Vågberg, Mattias, et al.
(författare)
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Brain parenchymal fraction in an age-stratified healthy population : determined by MRI using manual segmentation and three automated segmentation methods
- 2016
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Ingår i: Journal of neuroradiology. - : Masson Editeur. - 0150-9861 .- 1773-0406. ; 43:6, s. 384-391
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Brain atrophy is a prominent feature in many neurodegenerative diseases, such as multiple sclerosis, but age-related decrease of brain volume occurs regardless of pathological neurodegeneration. Changes in brain volume can be described by use of the brain parenchymal fraction (BPF), most often defined as the ratio of total brain parenchyma to total intracranial space. The BPF is of interest both in research and in clinical practice. To be able to properly interpret this variable, the normal range of BPF must be known. The objective of this study is to present normal values for BPF, stratified by age, and compare manual BPF measurement to three automated methods. MATERIALS AND METHODS: The BPFs of 106 healthy individuals aged 21 to 85 years were determined by the automated segmentation methods SyMap, VBM8 and SPM12. In a subgroup of 54 randomly selected individuals, the BPF was also determined by manual segmentation. RESULTS: The median (IQR) BPFs of the whole study population were 0.857 (0.064), 0.819 (0.028) and 0.784 (0.073) determined by SyMap, VBM8 and SPM12, respectively. The BPF decreased with increasing age. The correlation coefficients between manual segmentation and SyMap, VBM8 and SPM12 were 0.93 (P<0.001), 0.77 (P<0.001) and 0.56 (P<0.001), respectively. CONCLUSIONS: There was a clear relationship between increasing age and decreasing BPF. Knowledge of the range of normal BPF in relation to age group will help in the interpretation of BPF data. The automated segmentation methods displayed varying degrees of similarity to the manual reference, with SyMap being the most similar.
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| 6. |
- Vågberg, Mattias, et al.
(författare)
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Prediction of disability increase in a real world multiple sclerosis cohort
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- BACKGROUND Multiple sclerosis (MS) is an autoimmune disease characterized by demyelinating CNS-lesions and neurodegeneration. Brain atrophy measurements have been demonstrated to provide prognostic information. Assessment of brain atrophy via magnetic resonance imaging (MRI) using the Brain Parenchymal Fraction (BPF) was added to the clinical follow-up of individuals with MS at Umeå University Hospital in 2009/2010. OBJECTIVE To investigate whether an increase in disability, measured by a short to medium term increase in EDSS, can be predicted using clinically available variables. To assess if the previously described association between brain atrophy and disability could be detected in the setting of the clinical care program at Umeå University Hospital.METHODS All adult MS patients with simultaneous data on BPF, lesion count and EDSS at least at one occasion (n=278) were included. Individuals with two (n=163) and three (n=68) time points with complete data were used for testing the ability to predict Expanded Disability Status Scale (EDSS) score longitudinally. RESULTS The EDSS was found to correlate with BPF (p<0.001). Progressive disease course and early EDSS-worsening (SPMS), but no other clinical variables, could predict subsequent EDSS-worsening over follow-up times of approximately 1 to 4 years.CONCLUSION BPF was associated with concurrent EDSS, as previously described. Progressive disease course predicted risk for EDSS-increase but it was otherwise very difficult to predict increased disability in this treated MS-cohort. We discuss possible reasons for the lack of predictive value from clinically used variables in a treated MS cohort.
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