Publications by authors named "Laura Airas"

70 Publications

Pregnancy-Induced Changes in microRNA Expression in Multiple Sclerosis.

Front Immunol 2020 28;11:552101. Epub 2021 Jan 28.

Danish Multiple Sclerosis Center, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark.

Pregnancy affects the disease course in multiple sclerosis (MS), particularly in the third trimester, where the relapse rate is reduced by as much as two thirds. This study aimed at identifying changes in microRNA (miRNA) and immune cell phenotypes in pregnant MS patients. Discovery and validation studies to detect differentially expressed miRNAs were performed with quantitative real-time PCR on peripheral blood mononuclear cells (PBMC). Flow cytometry analysis was performed on PBMC stained with antibodies directed against surface markers of antigen presenting cells (APCs), NK-cells, NKT cells, CD4+ and CD8+ T cells and subsets of these cell types, including PDL1 and PDL2 expressing subsets. RNA was extracted from whole blood, monocytes, and NK-cells to investigate expression and correlation between regulated miRNAs and mRNAs. In total, 15 miRNAs were validated to be differentially expressed between third trimester pregnant and postpartum MS patients (Benjamini-Hochberg false discovery rate from p = 0.03-0.00004). Of these, 12 miRNAs were downregulated in pregnancy and 6 of the 15 miRNAs were altered by more than ±2-fold (+2.99- to -6.38-fold). Pregnant MS patients had a highly significant increase in the percentage of monocytes and a decrease of NK-cells and myeloid dendritic cells compared to non-pregnant MS patients. We confirm previous reports of a relative increase in CD56-bright NK-cells and a decrease in CD56-dim NK-cells in third trimester of pregnancy and report an increase in non-committed follicular helper cells. and expression was increased in pregnant patients together with . Also, in monocytes , , and were upregulated whereas miR-1, miR-20a, miR-28, miR-95, miR-146a, miR-335, and miR-625 were downregulated between pregnant and untreated MS patients. , , and were predicted targets of MS pregnancy-changed miRNAs, further supported by their negative correlations. Additionally, previously identified pregnancy-regulated mRNAs were identified as predicted targets of the miRNAs. PDL1 and PDL2 bind PD-1 expressed on T cells with an inhibitory effect on T-cell proliferation and increase in IL10 production. These results indicate that some of the effects behind the disease-ameliorating third trimester of pregnancy might be caused by changed expression of miRNAs and immunoregulatory molecules in monocytes.
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http://dx.doi.org/10.3389/fimmu.2020.552101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876450PMC
January 2021

Increased serum glial fibrillary acidic protein associates with microstructural white matter damage in multiple sclerosis: GFAP and DTI.

Mult Scler Relat Disord 2021 Feb 1;50:102810. Epub 2021 Feb 1.

Turku PET Centre, Turku, Finland; Clinical Neurosciences, University of Turku, Turku, Finland; Neurocenter, Turku University Hospital, Turku, Finland. Electronic address:

Background: Astrocytes and microglial cells are now recognized as active players in contributing to the diffuse neuroaxonal damage associated with disease progression of multiple sclerosis (MS). The serum level of glial fibrillary acidic protein (GFAP), a biomarker for astrocytic activation, is increased in MS and associates with disease progression and disability. Similarly, diffusion tensor imaging (DTI) parameters for microstructural changes in brain, including demyelination and axonal loss, associate with disability. The association between brain DTI parameters and serum GFAP has not been previously explored in MS. The objective of the study was to get insights into DTI-measurable pathological correlates of elevated serum GFAP in the normal appearing white matter (NAWM) of MS.

Methods: A total of 62 MS patients with median age of 49.2 years were included in the study. Study patients underwent DTI-MRI and blood sampling for GFAP determination by single molecule array (Simoa). Mean fractional anisotropy (FA) and mean (MD), axial (AD) and radial (RD) diffusivities were calculated within the entire NAWM and six segmented NAWM regions. The associations between the DTI parameters and GFAP levels were analysed using Spearman correlation analysis and multiple regression model with sex and disease modifying treatment (no, 1 line or 2 line) as adjustments.

Results: Elevated serum GFAP levels correlated significantly with decreased FA values within the entire (ρ = -0.39, p = 0.03), frontal (ρ = -0.42, p = 0.02), temporal (ρ = -0.37; p = 0.04) and cingulate (ρ = -0.38, p = 0.034) NAWM, and increased MD and RD within the frontal NAWM (ρ = 0.36, p = 0.046 for both). Similarly, higher GFAP associated with lower FA in frontal and cingulate NAWM in the multiple regression model corrected for confounding variables (standardised regression coefficient β = -0.29, p = 0.045 and β = -0.33, p = 0.025).

Conclusions: Our results give evidence that increased serum GFAP levels associate with DTI-measurable micro-damage in the NAWM in MS. Our work supports the use of serum GFAP as a biomarker for MS pathology-related astrocytopathy and related diffuse white matter damage.
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http://dx.doi.org/10.1016/j.msard.2021.102810DOI Listing
February 2021

Efficacy and tolerability of folate-aminopterin therapy in a rat focal model of multiple sclerosis.

J Neuroinflammation 2021 Jan 20;18(1):30. Epub 2021 Jan 20.

Turku PET Centre, University of Turku, Turku, Finland.

Background: Activated macrophages in the experimental model of multiple sclerosis (MS) express folate receptor-β (FR-β), representing a promising target for the treatment of MS. Here, we both evaluated the efficacy of a novel folate-aminopterin construct (EC2319) in a rat focal model of multiple sclerosis (MS) and investigated the utility of Ga-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid-conjugated folate (Ga-FOL) for assessing inflammatory lesions. In addition, we investigated whether FR-β is expressed in the brain of patients with MS.

Methods: Focal delayed-type hypersensitivity experimental autoimmune encephalomyelitis (fDTH-EAE) was induced in 40 Lewis rats; 20 healthy Lewis rats were used as controls. Rats were divided into six groups according to the duration of disease (control, acute, or chronic) and intervention (vehicle versus EC2319). Ga-FOL analyses, histology, and immunofluorescence of the brain were performed to evaluate the efficacy of subcutaneously administered EC2319 on lesion development. Immunofluorescence was used to assess FR-β expression in postmortem brain samples from 5 patients with MS and 5 healthy controls.

Results: Immunofluorescence and histological analyses revealed significant reductions in FR-β expression (P < 0.05) and lesion size (P < 0.01), as well as improved inducible nitric oxide synthase/mannose receptor C type 1 ratios (P < 0.01) in macrophages and microglia during the chronic but not acute phase of fDTH-EAE in EC2319-treated rats. The uptake of IV-injected Ga-FOL in the brain was low and did not differ between the groups, but the in vitro binding of Ga-FOL was significantly lower in EC2319-treated rats (P < 0.01). FR-β positivity was observed in chronically active lesions and in normal-appearing white matter in MS brain samples.

Conclusions: EC2319 was well tolerated and attenuated inflammation and lesion development in a rat model of a chronic progressive form of MS. Human MS patients have FR-β-positive cells in chronically active plaques, which suggests that these results may have translational relevance.
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http://dx.doi.org/10.1186/s12974-021-02073-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7819223PMC
January 2021

Fingolimod treatment reverses signs of diffuse white matter damage in multiple sclerosis: A pilot study.

Mult Scler Relat Disord 2021 Feb 15;48:102690. Epub 2020 Dec 15.

Turku PET Centre, University of Turku and Turku University Hospital, Turku, Finland; Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland.

Background: In multiple sclerosis (MS) diffuse normal appearing white matter (NAWM) damage may drive chronic worsening independent of relapse activity. Diffusion tensor imaging (DTI) is a nonconventional MRI technique that can be used to assess microstructural alterations in myelin and axons. The aim of our study was to investigate the effect of six months fingolimod treatment on the integrity of entire and segmented NAWM in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: Ten RRMS patients initiating fingolimod treatment were included in the study. Patients underwent 3 T MRI including diffusion tensor sequences at baseline before the initiation of treatment and at six months. The mean values for fractional anisotropy (FA), and mean, radial and axial diffusivities (MD, RD and AD) were calculated within the whole NAWM and in six segmented sub-regions of NAWM (frontal, parietal, temporal, occipital, cingulate and deep NAWM). Clinical characteristics, Expanded Disability Status Scale (EDSS) and volumetric MRI data were also evaluated.

Results: In the cingulate NAWM FA was increased and RD was decreased significantly at six months compared to baseline (0.462 vs. 0.472, P = 0.027 and 0.000646 vs. 0.000634, P = 0.041, respectively), indicating improvements in myelin and axonal integrity following fingolimod treatment, whereas there were no alterations in cingulate MD or AD. Cingulate and temporal FA and RD correlated with T2 lesion volume percentage of cingulate and temporal areas. EDSS change correlated with change of the whole NAWM AD.

Conclusions: Increased FA and decreased RD in the cingulate NAWM might suggest microstructural fingolimod-induced improvements in the normal appearing cingulate white matter. Our results support the concept that DTI can be used as a marker of diffuse neuronal damage also in interventional settings.
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http://dx.doi.org/10.1016/j.msard.2020.102690DOI Listing
February 2021

High serum neurofilament associates with diffuse white matter damage in MS.

Neurol Neuroimmunol Neuroinflamm 2021 01 8;8(1). Epub 2020 Dec 8.

From the Turku PET Centre, Turku University Hospital and University of Turku (M. Saraste, S.B., M.M., J.T., E.R., M. Sucksdorff, S.L., A.V., L.A.); Division of Clinical Neurosciences (E.R., M. Sucksdorff, S.L., A.V., L.A.), Turku University Hospital, Finland; and Departments of Medicine, Biomedicine and Clinical Research, Neurologic Clinic and Policlinic (J.K., D.L.), University Hospital Basel, Switzerland.

Objective: To evaluate to which extent serum neurofilament light chain (NfL) increase is related to diffusion tensor imaging-MRI measurable diffuse normal-appearing white matter (NAWM) damage in MS.

Methods: Seventy-nine patients with MS and 10 healthy controls underwent MRI including diffusion tensor sequences and serum NfL determination by single molecule array (Simoa). Fractional anisotropy and mean, axial, and radial diffusivities were calculated within the whole and segmented (frontal, parietal, temporal, occipital, cingulate, and deep) NAWM. Spearman correlations and multiple regression models were used to assess the associations between diffusion tensor imaging, volumetric MRI data, and NfL.

Results: Elevated NfL correlated with decreased fractional anisotropy and increased mean, axial, and radial diffusivities in the entire and segmented NAWM (for entire NAWM ρ = -0.49, = 0.005; ρ = 0.49, = 0.005; ρ = 0.43, = 0.018; and ρ = 0.48, = 0.006, respectively). A multiple regression model examining the effect of diffusion tensor indices on NfL showed significant associations when adjusted for sex, age, disease type, the expanded disability status scale, treatment, and presence of relapses. In the same model, T2 lesion volume was similarly associated with NfL.

Conclusions: Our findings suggest that elevated serum NfL in MS results from neuroaxonal damage both within the NAWM and focal T2 lesions. This pathologic heterogeneity ought to be taken into account when interpreting NfL findings at the individual patient level.
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http://dx.doi.org/10.1212/NXI.0000000000000926DOI Listing
January 2021

Frequency and etiology of acute transverse myelitis in Southern Finland.

Mult Scler Relat Disord 2020 Nov 7;46:102562. Epub 2020 Oct 7.

Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland. Electronic address:

Objective: Acute transverse myelitis is a relatively rare, frequently debilitating but potentially treatable emergency. The objective of this study was to evaluate the incidence and etiology of acute transverse myelitis in two major hospital districts in Southern Finland.

Methods: We identified all patients with acute transverse myelitis admitted to Turku University Hospital and Päijät-Häme Central hospital during nine years. The two hospitals serve a catchment area of 673,000 people in Southern Finland. Acute transverse myelitis was diagnosed according to the 2002 Transverse Myelitis Consortium Working Group. Patient files were reviewed for details of the clinical presentation and disease outcome, for laboratory findings and for neuroimaging. Charts were re-evaluated after an average of 7.7 years for confirmation of the acute transverse myelitis etiology.

Results: In total 63 patients fulfilled the Transverse Myelitis Consortium Working Group diagnostic criteria for acute transverse myelitis. The frequency of the condition was hence 1.04 cases/ 100,000 inhabitants/ year. In the studied cohort, 7/63 (11%) patients had idiopathic transverse myelitis after initial evaluation and in 4/63 (6.3%) patients the idiopathic transverse myelitis remained the final diagnosis after follow-up and re-evaluation. Of the disease-associated myelitis cases MS or clinically isolated syndrome was the largest group, explaining 41% of all myelitis cases. The mean follow-up time before a patient was diagnosed with MS was 1.7 ± 2.2 years. Other etiologies included acute disseminated encephalomyelitis (ADEM), neurosarcoidosis, neuromyelitis optica (NMO), systemic autoimmune diseases and infectious diseases.

Conclusions: In more than half of the acute transverse myelitis cases the final diagnosis is other than MS. Careful diagnostic work-up is needed for correct early treatment and best long-term outcome.
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http://dx.doi.org/10.1016/j.msard.2020.102562DOI Listing
November 2020

Brain TSPO-PET predicts later disease progression independent of relapses in multiple sclerosis.

Brain 2020 12;143(11):3318-3330

Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.

Overactivation of microglia is associated with most neurodegenerative diseases. In this study we examined whether PET-measurable innate immune cell activation predicts multiple sclerosis disease progression. Activation of microglia/macrophages was measured using the 18-kDa translocator protein (TSPO)-binding radioligand 11C-PK11195 and PET imaging in 69 patients with multiple sclerosis and 18 age- and sex-matched healthy controls. Radioligand binding was evaluated as the distribution volume ratio from dynamic PET images. Conventional MRI and disability measurements using the Expanded Disability Status Scale were performed for patients at baseline and 4.1 ± 1.9 (mean ± standard deviation) years later. Fifty-one (74%) of the patients were free of relapses during the follow-up period. Patients had increased activation of innate immune cells in the normal-appearing white matter and in the thalamus compared to the healthy control group (P = 0.033 and P = 0.003, respectively, Wilcoxon). Forward-type stepwise logistic regression was used to assess the best variables predicting disease progression. Baseline innate immune cell activation in the normal-appearing white matter was a significant predictor of later progression when the entire multiple sclerosis cohort was assessed [odds ratio (OR) = 4.26; P = 0.048]. In the patient subgroup free of relapses there was an association between macrophage/microglia activation in the perilesional normal-appearing white matter and disease progression (OR = 4.57; P = 0.013). None of the conventional MRI parameters measured at baseline associated with later progression. Our results strongly suggest that innate immune cell activation contributes to the diffuse neural damage leading to multiple sclerosis disease progression independent of relapses.
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http://dx.doi.org/10.1093/brain/awaa275DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7719021PMC
December 2020

Exposure to natalizumab during pregnancy and lactation is safe - No.

Authors:
Laura Airas

Mult Scler 2020 07 8;26(8):889-891. Epub 2020 Jun 8.

Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland; Department of Clinical Medicine, University of Turku, Turku, Finland/Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.

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http://dx.doi.org/10.1177/1352458520917934DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350191PMC
July 2020

Drug reaction with eosinophilia and systemic symptoms after ocrelizumab therapy.

Mult Scler Relat Disord 2020 Jul 14;42:102058. Epub 2020 Mar 14.

Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland. Electronic address:

We report here on a young woman with multiple sclerosis, who developed a condition with eosinophilia and swelling of limbs seven weeks after initiation of ocrelizumab treatment. We consider her drug reaction to be compatible with a drug reaction with eosinophilia and systemic symptoms (DRESS), also called drug-induced hypersensitivity syndrome. She was treated with antihistamine and corticosteroid treatments, and recovered fully within three months of symptom onset. Ocrelizumab was not re-initiated. We are not aware of other DRESS-like cases related to ocrelizumab treatment.
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http://dx.doi.org/10.1016/j.msard.2020.102058DOI Listing
July 2020

Oral doxycycline compared to intravenous ceftriaxone in the treatment of Lyme neuroborreliosis: a multicentre, equivalence, randomized, open-label trial.

Clin Infect Dis 2020 Mar 5. Epub 2020 Mar 5.

Department of Infectious Diseases, Turku University Hospital and University of Turku, Turku, Finland.

Background: Lyme neuroborreliosis (LNB) is often treated with intravenous ceftriaxone even if doxycycline is suggested to be non-inferior to ceftriaxone. We evaluated the efficacy of oral doxycycline in comparison to ceftriaxone in the treatment of LNB.

Methods: Patients with neurological symptoms suggestive of LNB without other obvious reasons were recruited. The inclusion criteria were: 1) production of B. burgdorferi specific antibodies in cerebrospinal fluid (CSF) or serum; or 2) B. burgdorferi DNA in the CSF; or 3) an erythema migrans during the past three months. Participants were randomized in 1:1 ratio to receive either oral doxycycline 100 mg twice a day for four weeks, or intravenous ceftriaxone 2 g daily for three weeks. The participants described their subjective condition with a visual analogue scale (VAS) from 0 to 10 (0 = normal; 10 = worst) before the treatment, and 4 and 12 months after the treatment. The primary outcome was the change in the VAS score at 12 months.

Results: Between Sep 14, 2012 and Dec 28, 2017, 210 adults with suspected LNB were assigned to receive doxycycline (n=104) or ceftriaxone (n=106). The per-protocol analysis comprised 82 patients with doxycycline and 84 patients with ceftriaxone. The mean change in the VAS score was -3.9 in the doxycycline group and -3.8 in the ceftriaxone group (mean difference 0.17 with 95% CI -0.59 - 0.92, which is within the pre-specified equivalence margins of -1 to 1 units). Participants in both groups improved equally.

Conclusions: Oral doxycycline is equally effective as intravenous ceftriaxone in the treatment of LNB.
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http://dx.doi.org/10.1093/cid/ciaa217DOI Listing
March 2020

Insights into disseminated MS brain pathology with multimodal diffusion tensor and PET imaging.

Neurol Neuroimmunol Neuroinflamm 2020 05 2;7(3). Epub 2020 Mar 2.

From the Turku PET Centre (S.B., J.T., M. Matilainen, A.V., M.N., S.S., M.S., M. Mohammadian, V.S., S.L., J.R., J.O.R., E.R., L.A.), University of Turku and Turku University Hospital; Division of Clinical Neurosciences (A.V., M.N., S.S., M.S., S.L., E.R., L.A.), Turku University Hospital; and Department of Medical Physics (V.S.), Division of Medical Imaging, Turku University Hospital, Finland.

Objective: To evaluate in vivo the co-occurrence of microglial activation and microstructural white matter (WM) damage in the MS brain and to examine their association with clinical disability.

Methods: 18-kDa translocator protein (TSPO) brain PET imaging was performed for evaluation of microglial activation by using the radioligand [C](R)-PK11195. TSPO binding was evaluated as the distribution volume ratio (DVR) from dynamic PET images. Diffusion tensor imaging (DTI) and conventional MRI (cMRI) were performed at the same time. Mean fractional anisotropy (FA) and mean (MD), axial, and radial (RD) diffusivities were calculated within the whole normal-appearing WM (NAWM) and segmented NAWM regions appearing normal in cMRI. Fifty-five patients with MS and 15 healthy controls (HCs) were examined.

Results: Microstructural damage was observed in the NAWM of the MS brain. DTI parameters of patients with MS were significantly altered in the NAWM compared with an age- and sex-matched HC group: mean FA was decreased, and MD and RD were increased. These structural abnormalities correlated with increased TSPO binding in the whole NAWM and in the temporal NAWM ( < 0.05 for all correlations; < 0.01 for RD in the temporal NAWM). Both compromised WM integrity and increased microglial activation in the NAWM correlated significantly with higher clinical disability measured with the Expanded Disability Status Scale score.

Conclusions: Widespread structural disruption in the NAWM is linked to neuroinflammation, and both phenomena associate with clinical disability. Multimodal PET and DTI allow in vivo evaluation of widespread MS pathology not visible using cMRI.
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http://dx.doi.org/10.1212/NXI.0000000000000691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136049PMC
May 2020

Rituximab in the treatment of multiple sclerosis in the Hospital District of Southwest Finland.

Mult Scler Relat Disord 2020 May 4;40:101980. Epub 2020 Feb 4.

Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland; Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland.

Background: There are already numerous B-cell depleting monoclonal anti-CD20 antibodies which have been used to reduce the inflammatory burden associated with multiple sclerosis (MS). We describe here our experience of treating MS-patients with B-cell depleting rituximab.

Patients And Methods: All MS-patients (n = 72) who had received rituximab treatment for at least six months by January 2019 were identified from the patient charts at the Turku University Hospital. Information about MS disease subtype, disease severity, MR-imaging outcomes and B-cell counts were collected from the charts.

Results: Rituximab was well received and well tolerated by the patients. There were no serious infusion-related side effects. The most serious adverse event that led to treatment discontinuation was neutropenia. After rituximab initiation the annual number of relapses was decreased in the relapsing remitting and secondary progressive MS groups and the mean number of gadolinium-enhancing lesions was decreased in relapsing remitting MS. Our study confirms the usability of rituximab treatment for MS in the Finnish health care environment.

Conclusions: Off-label rituximab-treatment can be successfully used to reduce MS disease burden for the benefit of MS patients.
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http://dx.doi.org/10.1016/j.msard.2020.101980DOI Listing
May 2020

Folate receptor-targeted positron emission tomography of experimental autoimmune encephalomyelitis in rats.

J Neuroinflammation 2019 Dec 3;16(1):252. Epub 2019 Dec 3.

Turku PET Centre, University of Turku, Turku, Finland.

Background: Folate receptor-β (FR-β) is a cell surface receptor that is significantly upregulated on activated macrophages during inflammation and provides a potential target for folate-based therapeutic and diagnostic agents. FR-β expression in central nervous system inflammation remains relatively unexplored. Therefore, we used focally induced acute and chronic phases of experimental autoimmune encephalomyelitis (EAE) to study patterns of FR-β expression and evaluated its potential as an in vivo imaging target.

Methods: Focal EAE was induced in rats using heat-killed Bacillus Calmette-Guérin followed by activation with complete Freund's adjuvant supplemented with Mycobacterium tuberculosis. The rats were assessed with magnetic resonance imaging and positron emission tomography/computed tomography (PET/CT) at acute (14 days) and chronic (90 days) phases of inflammation. The animals were finally sacrificed for ex vivo autoradiography of their brains. PET studies were performed using FR-β-targeting aluminum [F]fluoride-labeled 1,4,7-triazacyclononane-1,4,7-triacetic acid conjugated folate ([F]AlF-NOTA-folate, F-FOL) and 18 kDa translocator protein (TSPO)-targeting N-acetyl-N-(2-[C]methoxybenzyl)-2-phenoxy-5-pyridinamine (C-PBR28). Post-mortem immunohistochemistry was performed using anti-FR-β, anti-cluster of differentiation 68 (anti-CD68), anti-inducible nitric oxide synthase (anti-iNOS), and anti-mannose receptor C-type 1 (anti-MRC-1) antibodies. The specificity of F-FOL binding was verified using in vitro brain sections with folate glucosamine used as a blocking agent.

Results: Immunohistochemical evaluation of focal EAE lesions demonstrated anti-FR-β positive cells at the lesion border in both acute and chronic phases of inflammation. We found that anti-FR-β correlated with anti-CD68 and anti-MRC-1 immunohistochemistry; for MRC-1, the correlation was most prominent in the chronic phase of inflammation. Both F-FOL and C-PBR28 radiotracers bound to the EAE lesions. Autoradiography studies verified that this binding took place in areas of anti-FR-β positivity. A blocking assay using folate glucosamine further verified the tracer's specificity. In the chronic phase of EAE, the lesion-to-background ratio of F-FOL was significantly higher than that of C-PBR28 (P = 0.016).

Conclusion: Our EAE results imply that FR-β may be a useful target for in vivo imaging of multiple sclerosis-related immunopathology. FR-β-targeted PET imaging with F-FOL may facilitate the monitoring of lesion development and complement the information obtained from TSPO imaging by bringing more specificity to the PET imaging armamentarium for neuroinflammation.
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http://dx.doi.org/10.1186/s12974-019-1612-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6892159PMC
December 2019

Progressive dopaminergic defect in a patient with primary progressive multiple sclerosis.

Mult Scler Relat Disord 2019 Nov 7;36:101385. Epub 2019 Sep 7.

Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland; Department of Medical Physics, Turku University Hospital, Turku, Finland.

Dopamine has a modulatory role in a number of autoimmune diseases, but there are no published cases of longitudinal dopaminergic imaging in multiple sclerosis (MS). Here we report a patient with primary progressive multiple sclerosis (PPMS) who was scanned twice with brain dopamine transporter single photon emission computed tomography (SPECT) with an interval of four years. The results showed a loss of tracer binding that corresponded to a 4-7 fold steeper decline than in normal ageing. The finding points to a relevant role of nigrostriatal dopaminergic degeneration in the pathological process of PPMS.
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http://dx.doi.org/10.1016/j.msard.2019.101385DOI Listing
November 2019

Effects of age, BMI and sex on the glial cell marker TSPO - a multicentre [C]PBR28 HRRT PET study.

Eur J Nucl Med Mol Imaging 2019 Oct 30;46(11):2329-2338. Epub 2019 Jul 30.

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet and Stockholm County, Stockholm, Sweden.

Purpose: The purpose of this study was to investigate the effects of ageing, sex and body mass index (BMI) on translocator protein (TSPO) availability in healthy subjects using positron emission tomography (PET) and the radioligand [C]PBR28.

Methods: [C]PBR28 data from 140 healthy volunteers (72 males and 68 females; N = 78 with HAB and N = 62 MAB genotype; age range 19-80 years; BMI range 17.6-36.9) were acquired with High Resolution Research Tomograph at three centres: Karolinska Institutet (N = 53), Turku PET centre (N = 62) and Yale University PET Center (N = 25). The total volume of distribution (V) was estimated in global grey matter, frontal, temporal, occipital and parietal cortices, hippocampus and thalamus using multilinear analysis 1. The effects of age, BMI and sex on TSPO availability were investigated using linear mixed effects model, with TSPO genotype and PET centre specified as random intercepts.

Results: There were significant positive correlations between age and V in the frontal and temporal cortex. BMI showed a significant negative correlation with V in all regions. Additionally, significant differences between males and females were observed in all regions, with females showing higher V. A subgroup analysis revealed a positive correlation between V and age in all regions in male subjects, whereas age showed no effect on TSPO levels in female subjects.

Conclusion: These findings provide evidence that individual biological properties may contribute significantly to the high variation shown in TSPO binding estimates, and suggest that age, BMI and sex can be confounding factors in clinical studies.
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http://dx.doi.org/10.1007/s00259-019-04403-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717599PMC
October 2019

Natalizumab treatment reduces microglial activation in the white matter of the MS brain.

Neurol Neuroimmunol Neuroinflamm 2019 07 7;6(4):e574. Epub 2019 Jun 7.

Turku PET Centre (M.S., J.T., M.M., A.V., S.S., J.K., J. Rokka, M.N., J. Rinne, E.R., L.A.), Turku University Hospital and University of Turku; Division of Clinical Neurosciences (M.S., M.N., J. Rinne, E.R., L.A.), Turku University Hospital and University of Turku; and Department of Radiology (R.P.), University Hospital and University of Turku, Finland.

Objective: To evaluate whether natalizumab treatment reduces microglial activation in MS.

Methods: We measured microglial activation using the 18-kDa translocator protein (TSPO)-binding radioligand [C]PK11195 and PET imaging in 10 patients with MS before and after 1 year treatment with natalizumab. Microglial activation was evaluated as the distribution volume ratio (DVR) of the specifically bound radioligand in brain white and gray matter regions of interest. MRI and disability measurements were performed for comparison. Evaluation was performed identically with 11 age- and sex-matched patients with MS who had no MS therapy.

Results: Natalizumab treatment reduced microglial activation in the normal-appearing white matter (NAWM; baseline DVR vs DVR after 1 year of treatment 1.25 vs 1.22, = 0.014, Wilcoxon) and at the rim of chronic lesions (baseline DVR vs DVR after 1 year of treatment 1.24 vs 1.18, = 0.014). In patients with MS with no treatment, there was an increase in microglial activation at the rim of chronic lesions (1.23 vs 1.27, = 0.045). No alteration was observed in microglial activation in gray matter areas. In the untreated patient group, higher microglial activation at baseline was associated with more rapid disability progression during an average of 4 years of follow-up.

Conclusions: TSPO-PET imaging can be used as a tool to assess longitudinal changes in microglial activation in the NAWM and in the perilesional areas in the MS brain in vivo. Natalizumab treatment reduces the diffuse compartmentalized CNS inflammation related to brain resident innate immune cells.
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http://dx.doi.org/10.1212/NXI.0000000000000574DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624093PMC
July 2019

Serum glial fibrillary acidic protein correlates with multiple sclerosis disease severity.

Mult Scler 2020 02 20;26(2):210-219. Epub 2018 Dec 20.

Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland/Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland.

Background: Cerebrospinal fluid (CSF) levels of two soluble biomarkers, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), have been shown to associate with multiple sclerosis (MS) disease progression. Now, both biomarkers can be detected reliably in serum, and importantly, their serum levels correlate well with their CSF levels.

Objective: To evaluate the usability of serum GFAP measurement as a biomarker of progressive disease and disease severity in MS.

Methods: Clinical course, Expanded Disability Status Scale (EDSS), disease duration, patient age and magnetic resonance imaging (MRI) parameters were reviewed in 79 MS patients in this cross-sectional hospital-based study. Serum samples were collected for measurement of GFAP and NfL concentrations using single molecule array (Simoa) assay. A cohort of healthy controls was evaluated for comparison.

Results: Higher serum concentrations of both GFAP and NfL were associated with higher EDSS, older age, longer disease duration, progressive disease course and MRI pathology.

Conclusion: Earlier studies have demonstrated that GFAP, unlike NfL, is not increased in association with acute focal inflammation-related nervous system damage. Our work suggests that GFAP serum level associates with disease progression in MS and could potentially serve as an easily measurable biomarker of central nervous system (CNS) pathology related to disease progression in MS.
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http://dx.doi.org/10.1177/1352458518819380DOI Listing
February 2020

Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis.

Nat Commun 2018 12 17;9(1):5337. Epub 2018 Dec 17.

Department of Neurology, Yale School of Medicine, New Haven, CT, 06511, USA.

Epigenetic annotation studies of genetic risk variants for multiple sclerosis (MS) implicate dysfunctional lymphocytes in MS susceptibility; however, the role of central nervous system (CNS) cells remains unclear. We investigated the effect of the risk variant, rs7665090, located near NFKB1, on astrocytes. We demonstrated that chromatin is accessible at the risk locus, a prerequisite for its impact on astroglial function. The risk variant was associated with increased NF-κB signaling and target gene expression, driving lymphocyte recruitment, in cultured human astrocytes and astrocytes within MS lesions, and with increased lesional lymphocytic infiltrates and lesion sizes. Thus, our study establishes a link between genetic risk for MS (rs7665090) and dysfunctional astrocyte responses associated with increased CNS access for peripheral immune cells. MS may therefore result from variant-driven dysregulation of the peripheral immune system and of the CNS, where perturbed CNS cell function aids in establishing local autoimmune inflammation.
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http://dx.doi.org/10.1038/s41467-018-07785-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297228PMC
December 2018

Positron emission tomography imaging in evaluation of MS pathology in vivo.

Mult Scler 2018 10 9;24(11):1399-1412. Epub 2018 Aug 9.

Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland/Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland.

Positron emission tomography (PET) gives an opportunity to quantitate the expression of specific molecular targets in vivo and longitudinally in brain and thus enhances our possibilities to understand and follow up multiple sclerosis (MS)-related pathology. For successful PET imaging, one needs a relevant target molecule within the brain, to which a blood-brain barrier-penetrating specific radioligand will bind. 18-kDa translocator protein (TSPO)-binding radioligands have been used to detect activated microglial cells at different stages of MS, and remyelination has been measured using amyloid PET. Several PET ligands for the detection of other inflammatory targets, besides TSPO, have been developed but not yet been used for imaging MS patients. Finally, synaptic density evaluation has been successfully tested in human subjects and gives opportunities for the evaluation of the development of cortical and deep gray matter pathology in MS. This review will discuss PET imaging modalities relevant for MS today.
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http://dx.doi.org/10.1177/1352458518791680DOI Listing
October 2018

Vascular adhesion protein-1 is actively involved in the development of inflammatory lesions in rat models of multiple sclerosis.

J Neuroinflammation 2018 May 1;15(1):128. Epub 2018 May 1.

Turku PET Centre, University of Turku, Kiinamyllynkatu 4-8, FI-20520, Turku, Finland.

Background: Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial cell molecule and primary amine oxidase that mediates leukocyte entry to sites of inflammation. However, there is limited knowledge of the inflammation-related expression of VAP-1 in the central nervous system (CNS). Therefore, we investigated the expression of VAP-1 within the CNS vasculature in two focal rat models of experimental autoimmune encephalomyelitis (EAE) mimicking multiple sclerosis (MS).

Methods: EAE was induced either with Bacillus Calmette-Guérin, resulting in a delayed-type hypersensitivity-like pathogenesis (fDTH-EAE), or with myelin oligodendrocyte glycoprotein (fMOG-EAE). A subgroup of fMOG-EAE rats were treated daily with a selective VAP-1 inhibitor (LJP1586; 5 mg/kg). On 3 and 14 days after lesion activation, rat brains were assessed using magnetic resonance imaging (MRI), and ex vivo autoradiography was conducted to evaluate the binding of Gallium-68-labelled VAP-1 ligand. Histology and immunohistochemistry (OX-42, VAP-1, intercellular adhesion protein-1 [ICAM-1], P-selectin) supported the ex vivo autoradiography.

Results: EAE lesions showed MRI-detectable signal changes and binding of the VAP-1-targeting radiotracer in both rat models. Some of the VAP-1 positive vessels showed morphological features typical for high endothelial-like venules at sites of inflammation. Inhibition of VAP-1 activity with small molecule inhibitor, LJP1586, decreased lymphocyte density in the acute inflammatory phase of fMOG-EAE lesions (day 3, P = 0.026 vs. untreated), but not in the remission phase (day 14, P = 0.70 vs. untreated), and had no effect on the amount of OX-42-positive cells in either phase. LJP1586 treatment reduced VAP-1 and ICAM-1 expression in the acute inflammatory phase, whereas P-selectin remained not detectable at all studied stages of the disease.

Conclusions: Our results revealed that VAP-1 is expressed and functionally active in vasculature within the induced focal EAE lesions during the acute phase of inflammation and remains expressed after the acute inflammation has subsided. The study indicates that VAP-1 is actively involved in the development of inflammatory CNS lesions. During this process, the endothelial cell lesion-related vasculature seem to undergo a structural transformation from regular flat-walled endothelium to HEV-like endothelium.
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http://dx.doi.org/10.1186/s12974-018-1152-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5930736PMC
May 2018

Evaluation of Microglial Activation in Multiple Sclerosis Patients Using Positron Emission Tomography.

Front Neurol 2018 26;9:181. Epub 2018 Mar 26.

Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland.

Understanding the mechanisms underlying progression in multiple sclerosis (MS) is one of the key elements contributing to the identification of appropriate therapeutic targets for this under-managed condition. In addition to plaque-related focal inflammatory pathology typical for relapsing remitting MS there are, in progressive MS, widespread diffuse alterations in brain areas outside the focal lesions. This diffuse pathology is tightly related to microglial activation and is co-localized with signs of neurodegeneration. Microglia are brain-resident cells of the innate immune system and overactivation of microglia is associated with several neurodegenerative diseases. Understanding the role of microglial activation in relation to developing neurodegeneration and disease progression may provide a key to developing therapies to target progressive MS. 18-kDa translocator protein (TSPO) is a mitochondrial molecule upregulated in microglia upon their activation. Positron emission tomography (PET) imaging using TSPO-binding radioligands provides a method to assess microglial activation in patients . In this , we summarize the current status of TSPO imaging in the field of MS. In addition, the review discusses new insights into the potential use of this method in treatment trials and in clinical assessment of progressive MS.
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http://dx.doi.org/10.3389/fneur.2018.00181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879102PMC
March 2018

Hemophagocytic lymphohistiocytosis in 2 patients with multiple sclerosis treated with alemtuzumab.

Neurology 2018 05 30;90(18):849-851. Epub 2018 Mar 30.

From the Department of Neurology (M.S., P.J.T.), Helsinki University Hospital; Division of Clinical Neurosciences (M.S.-H., L.A.), Turku University Hospital, Finland; Department of Neurology (K.S., J.J., A.C.), Addenbrookes Hospital, University of Cambridge, UK; and Department of Neurology (J.T.S.), Vaasa Central Hospital, Finland.

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http://dx.doi.org/10.1212/WNL.0000000000005420DOI Listing
May 2018

Microglial activation, white matter tract damage, and disability in MS.

Neurol Neuroimmunol Neuroinflamm 2018 May 6;5(3):e443. Epub 2018 Mar 6.

Turku PET Centre (E.R., J.T., M.S., J.R., J.O.R.), Division of Clinical Neurosciences (E.R., M.S., J.O.R., L.A.), Department of Biostatistics (T.V.), and Medical Imaging Centre of Southwest Finland (T.P., R.P.), Turku University Hospital and University of Turku, Finland; Division of Neuroscience and Experimental Psychology (A.G.), University of Manchester, United Kingdom; Department of Nuclear Medicine and Geriatric Medicine (A.G.), University Hospital Essen, Germany; and Wolfson Molecular Imaging Centre (R.H., P.S.T.), University of Manchester, United Kingdom.

Objective: To investigate the relationship of in vivo microglial activation to clinical and MRI parameters in MS.

Methods: Patients with secondary progressive MS (n = 10) or relapsing-remitting MS (n = 10) and age-matched healthy controls (n = 17) were studied. Microglial activation was measured using PET and radioligand [C]()-PK11195. Clinical assessment and structural and quantitative MRI including diffusion tensor imaging (DTI) were performed for comparison.

Results: [C]()-PK11195 binding was significantly higher in the normal-appearing white matter (NAWM) of patients with secondary progressive vs relapsing MS and healthy controls, in the thalami of patients with secondary progressive MS vs controls, and in the perilesional area among the progressive compared with relapsing patients. Higher binding in the NAWM was associated with higher clinical disability and reduced white matter (WM) structural integrity, as shown by lower fractional anisotropy, higher mean diffusivity, and increased WM lesion load. Increasing age contributed to higher microglial activation in the NAWM among patients with MS but not in healthy controls.

Conclusions: PET can be used to quantitate microglial activation, which associates with MS progression. This study demonstrates that increased microglial activity in the NAWM correlates closely with impaired WM structural integrity and thus offers one rational pathologic correlate to diffusion tensor imaging (DTI) parameters.
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http://dx.doi.org/10.1212/NXI.0000000000000443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840890PMC
May 2018

PET Imaging of Adenosine 2A Receptors in Neuroinflammatory and Neurodegenerative Disease.

Contrast Media Mol Imaging 2017 20;2017:6975841. Epub 2017 Nov 20.

Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.

Adenosine receptors are G-protein coupled P1 purinergic receptors that are broadly expressed in the peripheral immune system, vasculature, and the central nervous system (CNS). Within the immune system, adenosine 2A (A) receptor-mediated signaling exerts a suppressive effect on ongoing inflammation. In healthy CNS, A receptors are expressed mainly within the neurons of the basal ganglia. Alterations in A receptor function and expression have been noted in movement disorders, and in Parkinson's disease pharmacological A receptor antagonism leads to diminished motor symptoms. Although A receptors are expressed only at a low level in the healthy CNS outside striatum, pathological challenge or inflammation has been shown to lead to upregulation of A receptors in extrastriatal CNS tissue, and this has been successfully quantitated using positron emission tomography (PET) imaging and A receptor-binding radioligands. Several radioligands for PET imaging of A receptors have been developed in recent years, and A receptor-targeting PET imaging may thus provide a potential additional tool to evaluate various aspects of neuroinflammation . This review article provides a brief overview of A receptors in healthy brain and in a selection of most important neurological diseases and describes the recent advances in A receptor-targeting PET imaging studies.
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http://dx.doi.org/10.1155/2017/6975841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5733838PMC
October 2018

Severe neutropenia after rituximab-treatment of multiple sclerosis.

Mult Scler Relat Disord 2018 Feb 12;20:3-5. Epub 2017 Dec 12.

Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland. Electronic address:

We present here the first MS-case where rituximab-treatment led to grade IV neutropenia, with hospitalization and treatment of a serious infection with broad-spectrum antibiotics. The neutropenia resolved promptly with granulocyte-colony stimulating factor-treatment and the patient recovered well. Due to risk of recurring neutropenia rituximab-treatment was not re-administered. We discuss the mechanisms and occurrence of neutropenia as a side effect to rituximab-treatment of MS, and remind of the importance of monitoring rituximab-treated MS-patients for this rare but potentially dangerous side effect.
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http://dx.doi.org/10.1016/j.msard.2017.12.005DOI Listing
February 2018

Botulinum toxin alleviates dysphagia of patients with inclusion body myositis.

J Neurol Sci 2017 Sep 24;380:142-147. Epub 2017 Jul 24.

Department of Otorhinolaryngology-Head and Neck Surgery, Turku University Hospital and University of Turku, Turku, Finland.

Objectives: Oropharyngeal dysphagia is a disabling and undertreated symptom that often occurs in patients with sporadic inclusion body myositis (s-IBM). In this study, we examined the effect of botulinum neurotoxin A (BoNT-A) injections to the cricopharyngeus muscle (CPM) of patients with s-IBM and dysphagia.

Patients, Materials And Methods: A single-center retrospective study involving 40 biopsy-proven s-IBM-patients treated in the District of Southwest Finland from 2000 to 2013. The incidence of dysphagia, rate of aspirations, rate of aspiration pneumonias and treatment results of dysphagia were analyzed. Patients treated for dysphagia were evaluated before and after surgery by video-fluoroscopy and/or using a questionnaire.

Results: Twenty-five of the 40 s-IBM patients (62.5%) experienced dysphagia. BoNT-A was injected a median of 2 times (range 1-7) in 12 patients with dysphagia. Before the injections 7 patients reported aspiration, none afterwards. The corresponding figures for aspiration pneumonia were 3 and 0. All of these patients had normal swallowing function 12months (median, range 2-60) after the last injection.

Conclusion: BoNT-A injections to the CPM alleviate the dysphagia of s-IBM patients reversibly and appear to reduce the rate of aspiration effectively.
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http://dx.doi.org/10.1016/j.jns.2017.07.031DOI Listing
September 2017

Evaluation of the Effect of Fingolimod Treatment on Microglial Activation Using Serial PET Imaging in Multiple Sclerosis.

J Nucl Med 2017 10 23;58(10):1646-1651. Epub 2017 Mar 23.

Division of Clinical Neurosciences, Turku University Hospital, Kiinamyllynkatu 4-8, Turku, Finland; and.

Traditionally, multiple sclerosis (MS) has been considered a white matter disease with focal inflammatory lesions. It is, however, becoming clear that significant pathology, such as microglial activation, also takes place outside the plaque areas, that is, in areas of normal-appearing white matter (NAWM) and gray matter (GM). Microglial activation can be detected in vivo using 18-kDa translocator protein (TSPO)-binding radioligands and PET. It is unknown whether fingolimod affects microglial activation in MS. The aim of this study was to investigate whether serial PET can be used to evaluate the effect of fingolimod treatment on microglial activation. Ten relapsing-remitting MS patients were studied using the TSPO radioligand C-()-PK11195. Imaging was performed at baseline and after 8 and 24 wk of fingolimod treatment. Eight healthy individuals were imaged for comparison. Microglial activation was evaluated as distribution volume ratio of C-()-PK11195. The patients had MS for an average of 7.9 ± 4.3 y (mean ± SD), their total relapses averaged 4 ± 2.4, and their Expanded Disability Status Scale was 2.7 ± 0.5. The patients were switched to fingolimod because of safety reasons or therapy escalation. The mean washout period before the initiation of fingolimod was 2.3 ± 1.1 mo. The patients were clinically stable on fingolimod. At baseline, microglial activation was significantly higher in the combined NAWM and GM areas of MS patients than in healthy controls ( 0.021). C-()-PK11195 binding was reduced (-12.31%) within the combined T2 lesion area after 6 mo of fingolimod treatment ( 0.040) but not in the areas of NAWM or GM. Fingolimod treatment reduced microglial/macrophage activation at the site of focal inflammatory lesions, presumably by preventing leukocyte trafficking from the periphery. It did not affect the widespread, diffuse microglial activation in the NAWM and GM. The study opens new vistas for designing future therapeutic studies in MS that use the evaluation of microglial activation as an imaging outcome measure.
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http://dx.doi.org/10.2967/jnumed.116.183020DOI Listing
October 2017

Natalizumab treatment leads to an increase in circulating CXCR3-expressing B cells.

Neurol Neuroimmunol Neuroinflamm 2016 Dec 24;3(6):e292. Epub 2016 Oct 24.

Department of Neurology (M.S), University of Turku; TYKSLAB (T.-L.P.), Laboratory of Clinical Haematology, Turku University Hospital; and Division of Clinical Neurosciences (L.A.), Turku University Hospital, and University of Turku, Finland.

Objective: To study the effects of natalizumab treatment on subgroups of circulating peripheral blood B cell populations.

Methods: We studied the proportions and absolute numbers of CD19CD20, CD10, and CD5 B cell populations, and determined very late activation antigen-4 and chemokine receptor CXCR3, CCR5, and CCR6 expression on B cells in the peripheral blood of 14 natalizumab-treated patients with relapsing-remitting multiple sclerosis. Five blood samples per patient were obtained longitudinally before and during the first year of treatment. Blood samples were analyzed by 6-color flow cytometry.

Results: Proportions of B cells and CD10 pre-B cells were significantly increased, and very late activation antigen-4 expression on the B cell surface was significantly decreased already after 1 week of natalizumab treatment. Natalizumab-induced sustained increase in the proportion and absolute number of CXCR3-expressing B cells was statistically significant after 1 month of treatment. There were no changes in the proportions of CCR5- or CCR6-expressing B cells.

Conclusions: The rapid and persistent increase in circulating CXCR3-expressing B cells in response to natalizumab treatment possibly reflects the relevance of this chemokine receptor in controlling migration of B cells into the CNS in humans in vivo.
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http://dx.doi.org/10.1212/NXI.0000000000000292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5079379PMC
December 2016

Imaging of microglial activation in MS using PET: Research use and potential future clinical application.

Mult Scler 2017 Apr 22;23(4):496-504. Epub 2016 Oct 22.

Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.

Multiple sclerosis (MS) is a complex disease, where several processes can be selected as a target for positron emission topography (PET) imaging. Unlike magnetic resonance imaging (MRI), PET provides specific and quantitative information, and unlike neuropathology, it can be non-invasively applied to living patients, which enables longitudinal follow-up of the MS pathology. In the study of MS, PET can be useful for in vivo evaluation of specific pathological characteristics at various stages of the disease. Increased understanding of the progressive MS pathology will enhance the treatment options of this undertreated condition. The ultimate goal of developing and expanding PET in the study of MS is to have clinical non-invasive in vivo imaging biomarkers of neuroinflammation that will help to establish prognosis and accurately measure response to therapeutics. This topical review provides an overview of the promises and challenges of the use of PET in MS.
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http://dx.doi.org/10.1177/1352458516674568DOI Listing
April 2017

Utilization of PET imaging in differential diagnostics between a tumefactive multiple sclerosis lesion and low-grade glioma.

Mult Scler Relat Disord 2016 Sep 26;9:147-9. Epub 2016 Jul 26.

Division of Clinical Neurosciences, Turku University Hospital and University of Turku, Turku, Finland; Turku PET Centre, Turku University Hospital and University of Turku, Turku, Finland.

We present a case where a 30-year-old man with a history of combined MS and Charcot-Marie-Tooth (CMT I) disease was additionally diagnosed and treated for grade II glioma (astrocytoma). Tumefactive MS and gliomas are sometimes difficult to distinguish from one another based on conventional magnetic resonance imaging (MRI). In our case, positron emission tomography (PET) scans with(11)C-methionine ((11)C-MET) and (11)C-PK11195 radioligands were performed to aid in differential diagnostics. The diagnosis was confirmed finally by brain biopsy. The usefulness of PET imaging in differential diagnostics between tumefactive MS and glioma is discussed.
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http://dx.doi.org/10.1016/j.msard.2016.07.016DOI Listing
September 2016