Publications by authors named "Viktoria Papp"

19 Publications

  • Page 1 of 1

Ocrelizumab treatment in multiple sclerosis: A Danish population-based cohort study.

Eur J Neurol 2021 Oct 13. Epub 2021 Oct 13.

The Danish Multiple Sclerosis Registry, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.

Background And Purpose: Real-world evidence regarding the effectiveness and safety of ocrelizumab for the treatment of multiple sclerosis (MS) is limited. The aim was to evaluate the effectiveness and safety of ocrelizumab treatment for MS in a real-world setting.

Methods: A nationwide population-based cohort study was conducted where clinical and magnetic resonance imaging data of MS patients enrolled prospectively in the Danish Multiple Sclerosis Registry who initiated ocrelizumab treatment between January 2018 and November 2020 were analyzed.

Results: A total of 1104 patients (85.7% relapsing-remitting MS [RRMS], 8.8% secondary progressive MS [SPMS], 5.5% primary progressive MS [PPMS]) were included, with a median follow-up period of 1.3 years. At baseline, the mean age was 41.4 years in the RRMS group, 44.5 years in the PPMS group and 50.3 years in the SPMS group. Median Expanded Disability Status Scale score was 2.5, 3.5 and 5.5, respectively. Most RRMS and SPMS patients had received previous disease-modifying therapies (87.5% and 91.8%, respectively), whereas PPMS patients were mostly treatment naïve (78.7%). After ocrelizumab initiation, 9.3% of the patients experienced a relapse and 8.7% a 24 weeks confirmed disability worsening. Conversely, 16.7% showed a 24 weeks confirmed disability improvement. After ~1 year of treatment, most patients (94.5%) were free of magnetic resonance imaging activity. Ocrelizumab was generally well tolerated, as side effects were only reported for 10% of patients, mostly consisting of infusion-related reactions and infections.

Conclusions: It is shown that most MS patients treated with ocrelizumab are clinically stabilized and with an adverse event profile consistent with the experience from the pivotal clinical trials.
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http://dx.doi.org/10.1111/ene.15142DOI Listing
October 2021

Associations Between Speaking Fundamental Frequency, Vowel Formant Frequencies, and Listener Perceptions of Speaker Gender and Vocal Femininity-Masculinity.

J Speech Lang Hear Res 2021 07 7;64(7):2600-2622. Epub 2021 Jul 7.

Christchurch, New Zealand.

Purpose The aim of the study was to examine associations between speaking fundamental frequency ( ), vowel formant frequencies (), listener perceptions of speaker gender, and vocal femininity-masculinity. Method An exploratory study was undertaken to examine associations between , - , listener perceptions of speaker gender (nominal scale), and vocal femininity-masculinity (visual analog scale). For 379 speakers of Australian English aged 18-60 years, mode and - (12 monophthongs; total of 36 s) were analyzed on a standard reading passage. Seventeen listeners rated speaker gender and vocal femininity-masculinity on randomized audio recordings of these speakers. Results Model building using principal component analysis suggested the 36 s could be succinctly reduced to seven principal components (PCs). Generalized structural equation modeling (with the seven PCs of and as predictors) suggested that only and predicted listener perceptions of speaker gender (male, female, unable to decide). However, listener perceptions of vocal femininity-masculinity behaved differently and were predicted by , , and the contrast between monophthongs at the extremities of the acoustic vowel space, in addition to and . Furthermore, listeners' perceptions of speaker gender also influenced ratings of vocal femininity-masculinity substantially. Conclusion Adjusted odds ratios highlighted the substantially larger contribution of to listener perceptions of speaker gender and vocal femininity-masculinity relative to than has previously been reported.
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http://dx.doi.org/10.1044/2021_JSLHR-20-00747DOI Listing
July 2021

Real-world outcomes for a complete nationwide cohort of more than 3200 teriflunomide-treated multiple sclerosis patients in The Danish Multiple Sclerosis Registry.

PLoS One 2021 18;16(5):e0250820. Epub 2021 May 18.

The Danish Multiple Sclerosis Registry, University Hospital Copenhagen, Rigshospitalet, Copenhagen, Denmark.

Objective: Teriflunomide is a once-daily, oral disease-modifying therapy (DMT) for relapsing forms of multiple sclerosis (MS). We studied clinical outcomes in a real-world setting involving a population-based large cohort of unselected patients enrolled in The Danish Multiple Sclerosis Registry (DMSR) who started teriflunomide treatment between 2013-2019.

Methods: This was a complete nationwide population-based cohort study with prospectively enrolled unselected cases. Demographic and disease-specific patient parameters related to treatment history, efficacy outcomes, and discontinuation and switching rates among other clinical variables were assessed at baseline and during follow-up visits.

Results: A total of 3239 patients (65.4% female) started treatment with teriflunomide during the study period, 56% of whom were treatment-naïve. Compared to previously treated patients, treatment-naïve patients were older on average at disease onset, had a shorter disease duration, a lower Expanded Disability Status Scale score at teriflunomide treatment start and more frequently experienced a relapse in the 12 months prior to teriflunomide initiation. In the 3001 patients initiating teriflunomide treatment at least 12 months before the cut-off date, 72.7% were still on treatment one year after treatment start. Discontinuations in the first year were due mainly to adverse events (15.6%). Over the full follow-up period, 47.5% of patients discontinued teriflunomide treatment. Sixty-three percent of the patients treated with teriflunomide for 5 years were relapse-free, while significantly more treatment-naïve versus previously treated patients experienced a relapse during the follow-up (p<0.0001). Furthermore, 85% of the patients with available data were free of disability worsening at the end of follow-up.

Conclusions: Solid efficacy and treatment persistence data consistent with other real-world studies were obtained over the treatment period. Treatment outcomes in this real-world scenario of the population-based cohort support previous findings that teriflunomide is an effective and generally well-tolerated DMT for relapsing MS patients with mild to moderate disease activity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250820PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130956PMC
November 2021

Population-based head-to-head comparison of the clinical characteristics and epidemiology of AQP4 antibody-positive NMOSD between two European countries.

Mult Scler Relat Disord 2021 Jun 3;51:102879. Epub 2021 Mar 3.

Department of Neurology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.

Background: Population-based clinical studies in neuromyelitis optica spectrum disorder (NMOSD) and epidemiological and clinical comparisons of White ethnicities are missing. In a large population-based international cohort, we extensively characterized aquaporin-4 antibody seropositive (AQP4-Ab+) NMOSD, and also compared the clinical, radiological and epidemiological features between two European populations residing in different areas.

Methods: Between self-reported Danish and Hungarian ethnicities, we compared the population-based clinical features, disability outcomes, and death of 134 AQP4-Ab+ NMOSD cases fulfilling the 2015 International Panel for NMO Diagnosis (IPND) criteria. For precise comparison of epidemiology, we conducted a population-based head-to-head comparative study of the age-standardized prevalence (January 1, 2014) and incidence (2007-2013) of AQP4-Ab+ NMO/NMOSD among adults (≥16 years) in Denmark (4.6 million) and Hungary (6.4 million) by applying 2015 IPND (NMOSD) criteria and 2006 Wingerchuk (NMO).

Results: Danes were more likely to present with transverse myelitis and were more affected by spinal cord damage on long-term disability. Hungarians presented most often with optic neuritis, although visual outcome was similar in the groups. No differences were observed in sex, disease course, relapse rate, autoimmune comorbidity, mortality, brain MRI, and treatment strategies. The age-standardized prevalence estimates of AQP4-Ab+ NMOSD (2015 IPND criteria) in Denmark vs. Hungary were 0.66 vs. 1.43 (/100,000) while incidence rates were 0.04 vs. 0.11 (/100,000 person-years); similar differences were found based on the 2006 NMO criteria.

Conclusions: This head-to-head comparative study indicates different disease characteristics and epidemiology among White populations in Europe, and substantiates the need for population-based genetic and environmental studies in NMOSD.
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http://dx.doi.org/10.1016/j.msard.2021.102879DOI Listing
June 2021

Worldwide Incidence and Prevalence of Neuromyelitis Optica: A Systematic Review.

Neurology 2021 01 11;96(2):59-77. Epub 2020 Dec 11.

From the Department of Neurology (V.P., Z.I.), Odense University Hospital; Danish Multiple Sclerosis Center (M.M.), Copenhagen University Hospital, Rigshospitalet, Denmark; Department of Neurology (O.A.), Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany; Department of Neurology (T.B.), Medical University of Vienna, Austria; Menzies Health Institute Queensland (S.A.B.), Griffith University, Gold Coast; Department of Neurology (S.A.B.), Gold Coast University Hospital, Australia; Department of Neurology (P.C.), Fort-de-France University Hospital Center, Pierre Zobda Quitman Hospital, Fort-de-France, Martinique, France; Department of Neurology (A.J.), The Walton Centre, Liverpool, UK; Cleveland Clinic (A.J.), Abu Dhabi, United Arab Emirates; Departments of Neurology (J.K., J.P.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Nuffield Department of Clinical Neurosciences (M.I.L., J.P.), John Radcliffe Hospital, University of Oxford, UK; Service de Neurologie (R.M.), Sclérose en Plaques, Pathologies de la Myéline et Neuro-Inflammation, et Centre de Référence des Maladies Inflammatoires Rares du Cerveau et de la Moelle (MIRCEM), Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, Bron, France; Department of Neurology (K.M.), Kindai University Graduate School of Medicine, Osaka, Japan; Center of Neuroimmunology (A.S., M.S.), Service of Neurology, Hospital Clínic of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Spain; Department of Neurology (O.S.), Karolinska University Hospital and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Institute of Clinical Research (Z.I.), University of Southern Denmark, Odense, Denmark; and Institute of Molecular Medicine (Z.I.), University of Southern Denmark, Odense.

Objective: Since the last epidemiologic review of neuromyelitis optica/neuromyelitis optica spectrum disorder (NMO/NMOSD), 22 additional studies have been conducted. We systematically review the worldwide prevalence, incidence, and basic demographic characteristics of NMOSD and provide a critical overview of studies.

Methods: PubMed, Ovid MEDLINE, and Embase using Medical Subject Headings and keyword search terms and reference lists of retrieved articles were searched from 1999 until August 2019. We collected data on the country; region; methods of case assessment and aquaporin-4 antibody (AQP4-Ab) test; study period; limitations; incidence (per 100,000 person-years); prevalence (per 100,000 persons); and age-, sex-, and ethnic group-specific incidence or prevalence.

Results: We identified 33 relevant articles. The results indicated the highest estimates of incidence and prevalence of NMOSD in Afro-Caribbean region (0.73/100 000 person-years [95% CI: 0.45-1.01] and 10/100 000 persons [95% CI: 6.8-13.2]). The lowest incidence and prevalence of NMOSD were found in Australia and New Zealand (0.037/100 000 person-years [95% CI: 0.036-0.038] and 0.7/100,000 persons [95% CI: 0.66-0.74]). There was prominent female predominance in adults and the AQP4-Ab-seropositive subpopulation. The incidence and prevalence peaked in middle-aged adults. African ethnicity had the highest incidence and prevalence of NMOSD, whereas White ethnicity had the lowest. No remarkable trend of incidence was described over time.

Conclusion: NMOSD is a rare disease worldwide. Variations in prevalence and incidence have been described among different geographic areas and ethnicities. These are only partially explained by different study methods and NMO/NMOSD definitions, highlighting the need for specifically designed epidemiologic studies to identify genetic effects and etiologic factors.
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http://dx.doi.org/10.1212/WNL.0000000000011153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7905781PMC
January 2021

Formant Frequencies of Adult Speakers of Australian English and Effects of Sex, Age, Geographical Location, and Vowel Quality.

J Voice 2020 Oct 22. Epub 2020 Oct 22.

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Cardiovascular Research Institute, National University Heart Centre Singapore, National University Health System, Singapore; Department of Mathematics and Statistics, La Trobe University, Melbourne, Victoria, Australia.

Aims: The primary aim of this study was to provide normative formant frequency (F) values for male and female speakers of Australian English. The secondary aim was to examine the effects of speaker sex, age, vowel quality, and geographical location on F.

Method: The first three monophthong formant frequencies (F, F, and F) for 244 female and 135 male speakers aged 18-60 years from a recent large-scale corpus of Australian English were analysed on a passage reading task.

Results: Mixed effects linear regression models suggested that speaker sex, speaker age, and vowel quality significantly predicted F, F, and F (P = 0.000). Effect sizes suggested that speaker sex and vowel quality contributed most to the variations in F, F, and F whereas speaker age and geographical location contributed a smaller amount.

Conclusion: Both clinicians and researchers are provided with normative F data for 18-60 year-old speakers of Australian English. Such data have increased internal and external validity relative to previous literature. F normative data for speakers of Australian English should be considered with reference to speaker sex and vowel but it may not be practically necessary to adjust for speaker age and geographical location.
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http://dx.doi.org/10.1016/j.jvoice.2020.09.026DOI Listing
October 2020

Speaking Fundamental Frequencies of Adult Speakers of Australian English and Effects of Sex, Age, and Geographical Location.

J Voice 2020 Jul 27. Epub 2020 Jul 27.

Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Cardiovascular Research Institute, National University Heart Centre Singapore, National University Health System, Singapore; Department of Mathematics & Statistics, La Trobe University, Melbourne, Victoria, Australia.

Aims: The aim of this study was to provide a description of normative speaking fundamental frequency (f) characteristics for adult speakers of Australian English. The effects of age, sex, and geographical location on f were also examined to assess whether variations existed.

Methods: f data for 244 female and 135 male speakers aged 18-60 years from a recent large-scale corpus of Australian English were analyzed on a passage reading task. Creak phonation frequencies were first separated from the modal phonation frequencies algorithmically. Descriptive statistics were then generated for modal voice.

Results: The mixed effects linear regression model suggested that geographical location had no effect on f (P = 0.0677). The multiple linear regression model suggested that both sex (P = 0.000) and age (P = 0.000) significantly predicted f. f of the female speakers was greater than males by 76 Hz, when accounted for by age, and for every increase in age by one year, f decreased by 0.37 Hz. Normative data on f were therefore provided with reference to speaker sex and age only.

Conclusion: Both clinicians and researchers are provided with normative f data for 18-60 year-old speakers of Australian English. These updated data have increased internal and external validity relative to previous literature. These increases were achieved by having a larger sample size, systematically sampling speakers of different age groups and geographical locations, sampling contemporary speakers of Australian English and excluding speakers with known concomitant factors that affect f.
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http://dx.doi.org/10.1016/j.jvoice.2020.06.014DOI Listing
July 2020

Initial high-efficacy disease-modifying therapy in multiple sclerosis: A nationwide cohort study.

Neurology 2020 08 7;95(8):e1041-e1051. Epub 2020 Jul 7.

From the Danish Multiple Sclerosis Registry (M.D.B., T.A.C., M.M.) and Danish Multiple Sclerosis Center (M.D.B., T.A.C., F.S., J.R.C., R.C., P.S.S., M.M.), Department of Neurology, Rigshospitalet; Department of Neurology (I.B., V.H., J.S.), Aalborg University Hospital; Department of Neurology (M.K.C., T.P., P.V.R.), Aarhus University Hospital; Department of Neurology (Z.I., V.P., Á.T.), Odense University Hospital; Brain and Nerve Diseases (H.B.J.), Lillebaelt Hospital, Kolding; Institute of Regional Health Research (H.B.J.), University of Southern Denmark, Odense; Department of Neurology (M.K.), Hospital of Southern Jutland, Sønderborg; and Department of Neurology (A.W.), Herlev Hospital, Denmark.

Objective: To determine the effectiveness of high-efficacy disease-modifying therapies (heDMTs) vs medium-efficacy disease-modifying therapies (meDMT) as the first treatment choice in treatment-naive patients with multiple sclerosis (MS) on disability worsening and relapses. We assessed this using a nationwide population-based MS registry.

Methods: We identified all patients starting a heDMT as first-time treatment from the Danish Multiple Sclerosis Registry and compared treatment outcomes with a propensity score matched sample of patients starting meDMT.

Results: We included 388 patients in the study: 194 starting initial therapy with heDMT matched to 194 patients starting meDMT. At 4 years of follow-up, the probabilities of a 6-month confirmed Expanded Disability Status Scale (EDSS) score worsening were 16.7% (95% confidence interval [CI] 10.4%-23.0%) and 30.1% (95% CI 23.1%-37.1%) for heDMT and meDMT initiators, respectively (hazard ratio [HR] 0.53, 95% CI 0.33-0.83, = 0.006). Patients initiating heDMT also had a lower probability of a first relapse (HR 0.50, 95% CI 0.37-0.67). Results were similar after pairwise censoring and in subgroups with high baseline activity, diagnosis after 2006, or information on baseline T2 lesion load.

Conclusion: We found a lower probability of 6-month confirmed EDSS score worsening and lower probability of a first relapse in patients starting a heDMT as first therapy, compared to a matched sample starting meDMT.

Classification Of Evidence: This study provides Class III evidence that for patients with MS, starting heDMT lowers the risk of EDSS worsening and relapses compared to starting meDMT.
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http://dx.doi.org/10.1212/WNL.0000000000010135DOI Listing
August 2020

The roles of language use and vocabulary size in the emergence of word-combining in children with complex neurodevelopmental disabilities.

J Child Lang 2021 01 28;48(1):202-214. Epub 2020 May 28.

University of Canterbury, New Zealand Institute of Language, Brain and Behaviour.

Parent report data on 82 preschool children with complex neurodevelopmental disabilities including Down syndrome, dyspraxia, autism, and global developmental delay suggests communicative language use must reach a threshold level before vocabulary size becomes the best predictor of word combining. Using the Language Use Inventory and the MacArthur-Bates CDI (with sign vocabulary option), statistical modelling using regression trees and random forests suggests that, despite high linear correlations between variables, (1) pragmatic ability, particularly children's emerging ability to talk about things, themselves and others is a significantly better predictor of the earliest word combining than vocabulary size; and (2) vocabulary size becomes a better predictor of later word combining, once this pragmatic base has been established.
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http://dx.doi.org/10.1017/S0305000920000136DOI Listing
January 2021

Clinically stable disease is associated with a lower risk of both income loss and disability pension for patients with multiple sclerosis.

J Neurol Neurosurg Psychiatry 2020 01 14;91(1):67-74. Epub 2019 Nov 14.

Danish Multiple Sclerosis Center, Department of Neurology, University of Copenhagen, Rigshospitalet Glostrup, Copenhagen, Denmark.

Objective: To assess the risk of losing income from salaries and risk disability pension for multiple sclerosis patients with a clinically stable disease course 3 years after the start of disease-modifying therapy (DMT).

Methods: Data from the Danish Multiple Sclerosis Registry were linked to other Danish nationwide population-based databases. We included patients who started treatment with a DMT between 2001 and 2014. Patients were categorised into a clinically stable group (No Evidence of Disease Activity (NEDA-2)) and a clinically active group (relapse activity or 6-month confirmed Expanded Disability Status Scale worsening). Outcomes were: (1) loss of regular income from salaries and (2) a transfer payment labelled as disability pension. We used a Cox proportional hazards model to estimate confounder-adjusted HRs, and absolute risks were plotted using cumulative incidence curves accounting for competing risks.

Results: We included 2406 patients for the income analyses and 3123 patients for the disability pension analysis. Median follow-up from index date was ~5 years in both analyses. The NEDA-2 group had a 26% reduced rate of losing income (HR 0.74; 95% CI 0.60 to 0.92). HRs were calculated for 5-year intervals in the disability pension analysis: year 0-5: a 57% reduced rate of disability pension for the NEDA-2 group (HR 0.43; 95% CI 0.33 to 0.55) and year 5-10: a 36% reduced rate (HR 0.64; 95% CI 0.40 to 1.01).

Conclusion: Clinically stable disease course (NEDA-2) is associated with a reduced risk of losing income from salaries and a reduced risk of disability pension.
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http://dx.doi.org/10.1136/jnnp-2019-321523DOI Listing
January 2020

Nationwide prevalence and incidence study of neuromyelitis optica spectrum disorder in Denmark.

Neurology 2018 12 9;91(24):e2265-e2275. Epub 2018 Nov 9.

From the Department of Neurology (V.P., K.S., T.P.), Aarhus University Hospital; Department of Neurology (Z.I., H.H.N.), Odense University Hospital; Institute of Clinical Research (Z.I., H.H.N.), Institute of Molecular Biology (H.H.N.), and Department of Regional Health Research, Faculty of Health Sciences (E.S.), University of Southern Denmark, Odense; The Danish Multiple Sclerosis Center (M.M., P.E.H.J., F.S.), Department of Neurology, Rigshospitalet, University of Copenhagen; The Danish Multiple Sclerosis Registry (M.M., N.K.-H.), Department of Neurology, Rigshospitalet, Copenhagen University Hospital; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), and Department of Biomedicine (T.C.), Aarhus University; MS-Clinic of Southern Jutland (Sønderborg, Esbjerg, Kolding) (M.K., E.S.), Department of Neurology, Hospital of Southern Jutland, Sønderborg; Department of Neurology (C.C.P., Z.M.), Aalborg University Hospital; Multiple Sclerosis Unit (S.F.R.), Department of Neurology, Herlev Hospital, Copenhagen; Department of Neurology (M.B.J.), Nordsjællands Hospital, Hillerød; Department of Neurology (A.E.P.), Hospital of Southwest Jutland, Esbjerg; Department of Neurology (L.R.), Hospital of Central Denmark Region, Viborg; Department of Autoimmunology and Biomarkers (M.C.L., N.H.), Statens Serum Institut, Copenhagen; and Department of Neurology (J.L.F.), Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Glostrup, Denmark.

Objectives: To estimate the nationwide population-based incidence, prevalence, and geographical distribution of neuromyelitis optica (NMO) spectrum disorder (NMOSD) in Denmark based on the 2015 International Panel for NMO Diagnosis (IPND) criteria.

Methods: We conducted a multicentre, historically prospective study. Data were sourced from the Danish National Patient Registry, the Danish Multiple Sclerosis Registry, departments of neurology, and laboratories providing aquaporin-4 antibody test. Cases were selected based on the 2006 Wingerchuk and the 2015 IPND criteria and were individually validated by an expert panel.

Results: We confirmed NMO in 30 cases (2006 criteria) and NMOSD in 56 cases (2015 IPND criteria) between 2007 and 2014. Defined by the 2006 criteria, the incidence of NMO was 0.029 per 100,000 person-years (95% confidence interval [CI] 0.014-0.051), and the prevalence (aged 16 years and older) was 0.566 per 100,000 (95% CI 0.370-0.830). Based on the 2015 IPND criteria, the incidence of NMOSD was 0.070 per 100,000 person-years (95% CI 0.046-0.102), and the prevalence (aged 16 years and older) was 1.09 per 100,000 (95% CI 0.808-1.440), without regional differences.

Conclusions: Our estimates of incidence and prevalence are similar to other Caucasian population-based studies using the 2015 IPND criteria. We found no geographical clustering in Denmark.
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http://dx.doi.org/10.1212/WNL.0000000000006645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6329324PMC
December 2018

Clinical utility of anti-MOG antibody testing in a Danish cohort.

Mult Scler Relat Disord 2018 Nov 11;26:61-67. Epub 2018 Sep 11.

Danish Multiple Sclerosis Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, Copenhagen 2100, Denmark.

Background: Anti-myelin oligodendrocyte glycoprotein (MOG) antibody (Ab) can be found in different immune-mediated inflammatory CNS disorders. The full range of clinical manifestations may not have been fully discovered yet.

Methods: In a cross-sectional study 184 adults (age ≥ 16) were tested for anti-MOG antibody (Ab) with a cell-based assay. To define the relevant target population for anti-MOG antibody testing in a neurology clinic, we divided the entire study population based on the presenting symptoms and classified cases followed for multiple sclerosis (MS) according to the clinical features and response to disease-modifying therapy.

Results: We identified eight (4.4%) MOG-Ab positive cases in the whole cohort. All eight cases had first manifestations suggestive of neuromyelitis optica spectrum disorder (NMOSD), but had highly variable disease courses and responses to therapy. This included a patient with chronic relapsing inflammatory optic neuropathy (CRION) responding only to therapy with infliximab. Four (3%) out of 134 cases followed for MS who tested positive for anti-MOG Ab showed atypical features and had poor response to therapy.

Conclusion: A broad range of clinical and radiological features of anti-MOG associated disorder was observed in a single centre. MOG-Ab testing should be considered in patients with an NMOSD phenotype and in MS patients presenting atypical features. The potential use of infliximab therapy for MOG-Ab disease should be further investigated.
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http://dx.doi.org/10.1016/j.msard.2018.09.010DOI Listing
November 2018

Early Dynamics of P-selectin and Interleukin 6 Predicts Outcomes in Ischemic Stroke.

J Stroke Cerebrovasc Dis 2015 Aug 4;24(8):1938-47. Epub 2015 Jun 4.

Department of Neurology, University of Pecs, Pecs, Hungary; Department of Neurology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address:

Background: Thromboinflammatory molecules connect the prothrombotic state, endothelial dysfunction, and systemic/local inflammation in the acute phase of ischemic stroke.

Methods: We prospectively investigated (1) serial changes in the levels of thromboinflammatory biomarkers in 76 patients with acute ischemic stroke (6, 24, and 72 hours after onset); (2) compared with 44 patients with asymptomatic severe (≥70%) carotid stenosis and 66 patients with Parkinson disease; and (3) we applied multiple regression methods, relating biological biomarkers combined with demographic data and comorbidities to poststroke infection, death, and functional outcome, and assessed the ability of the models to predict each outcome.

Results: Interleukin 6 (IL-6) levels and change of IL-6 concentrations by 72 hours correlated with the size of tissue damage indicated by S100B titers. Levels of IL-6 and P-selectin at 72 hours were higher in patients with large-artery versus lacunar stroke. High concentration of IL-6, monocyte chemotactic protein 1, and S100B at 6 hours were associated with poststroke infections; high concentration of IL-6, S100B, and high-sensitivity C-reactive protein (hsCRP) correlated with death. Change of P-selectin from 6 to 72 hours by 1 unit increased the incidence of poststroke infections with an odds ratio of 22.7; each 100 units of IL-6 at baseline increased the odds of death by 9‰, and at 72 hours, the odds of poststroke infections by 4‰. Each unit of baseline hsCRP elevated the odds of death by 7%.

Conclusions: In regression models, in which biological, demographic, and comorbid factors were combined, those biological biomarkers predicted poor outcome with high accuracy, which were characterized by an increasing concentration by 72 hours. Two particular biomarkers emerged to predict outcomes besides hsCRP: early dynamic changes in the systemic levels of P-selectin and IL-6.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2015.05.005DOI Listing
August 2015

The L-arginine pathway in acute ischemic stroke and severe carotid stenosis: temporal profiles and association with biomarkers and outcome.

J Stroke Cerebrovasc Dis 2014 Sep 10;23(8):2206-2214. Epub 2014 Jul 10.

Department of Neurology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.

Background: Endothelial dysfunction is associated with increased levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) resulting in a decreased production of nitric oxide, which regulates the vascular tone.

Methods: Patients with acute ischemic stroke (AIS, n = 55) and asymptomatic significant carotid stenosis (AsCS, n = 44) were prospectively investigated. L-arginine, ADMA, SDMA, S100 B, and high-sensitivity C-reactive protein (hsCRP) were serially measured within 6 hours after the onset of stroke, at 24 and 72 poststroke hours. All markers were compared with healthy subjects (n = 45). The severity of AIS was daily assessed by National Institute of Health Stroke Scale scoring.

Results: Even within 6 hours after the onset of stroke, L-arginine, ADMA, and SDMA were significantly higher in patients with AIS compared with both AsCS and healthy subjects. S100 B reflecting infarct size, positively correlated with the level of SDMA at 72 poststroke hours; changes in concentration of S100 B positively correlated with changes in the concentration of ADMA by 72 hours. Change in concentration of both ADMA and SDMA correlated with the change in concentration of hsCRP. Concentrations of L-arginine and hsCRP at 72 poststroke hours, respectively, were independent predictors of poststroke infection. S100 B level measured within 6 hours after the onset of AIS and hsCRP at 72 poststroke hours were independent predictors of death.

Conclusions: Metabolites of the L-arginine pathway were elevated in the very acute phase of ischemic stroke indicating a more pronounced endothelial dysfunction compared with AsCS. An increased basal L-arginine level in patients with AIS might be an adaptive mechanism; such transient elevation of the L-arginine/ADMA ratio at 24 poststroke hours may suggest that a temporary increase of L-arginine along with decrease of ADMA might be related to the protective role of L-arginine. Changes in the L-arginine pathway are predictive of poststroke infections.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.05.002DOI Listing
September 2014

Chemomechanical preparation by hand instrumentation and by Mtwo engine-driven rotary files, an ex vivo study.

J Clin Exp Dent 2012 Jul 1;4(3):e146-50. Epub 2012 Jul 1.

DMD, PhD. Professor. Dental School, Faculty of Medicine, University of Pécs, Hungary.

Objective: To compare the disinfecting efficacy of the sodium hypochlorite irrigation by root canal preparation with stainless steel hand files, taper 0.02 and nickel-titanium Mtwo files with taper 0.04-0.06.

Study Design: 40 extracted human teeth were sterilized, and then inoculated with Enterococcus faecalis (ATCC 29212). After 6 day incubation time the root canals were prepared by hand with K-files (n=20) and by engine-driven Mtwo files (VDW, Munich, Germany) (n=20). Irrigation was carried out with 2.5% NaOCl in both cases. Samples were taken and determined in colony forming units (CFU) from the root canals before and after the preparation with instruments #25 and #35.

Results: Significant reduction in bacterial count was determined after filing at both groups. The number of bacteria kept on decreasing with the extension of apical preparation diameter. There was no significant difference between the preparation sizes in the bacterial counts after hand or engine-driven instrumentation at the same apical size. Statistical analysis was carried out with Mann-Whitney test, paired t-test and independent sample t-test.

Conclusions: Significant reduction in CFU was achieved after the root canal preparation completed with 2.5% NaOCl irrigation, both with stainless steel hand or nickel-titanium rotary files. The root canal remained slightly infected after chemo mechanical preparation in both groups. Key words:Chemomechanical preparation, root canal disinfection, nickel-titanium, conicity, greater taper, apical size.
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http://dx.doi.org/10.4317/jced.50733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3917638PMC
July 2012

[Immune responses and neuroimmune modulation in the pathogenesis of acute ischemic stroke and poststroke infections].

Ideggyogy Sz 2010 Jul;63(7-8):232-46

Neurológiai Klinika, Pécsi Tudományegyetem, Pécs.

Acute-onset cerebrovascular diseases are connected to a number of immunological changes. Here, we summarize immune responses participating in the evolution of atherosclerotic plaques and poststroke local immune responses in the injured CNS as well as in the systemic circulation. Ischemic injury of the CNS alters the balanced neuroimmune modulation resulting in CIDS, the central nervous system injury-induced immune deficiency syndrome. Due to the immunodepression and reduced pro-inflammatory immune responses, the susceptibility for infection is increased; indeed, poststroke infection plays a major role in stroke-related mortality. On the other hand, CIDS may protect against damaging autoimmune responses elicited by exposed CNS antigens. Investigation of immune responses related to ischemic stroke may result in novel therapies indicated by an increasing number of experimental and clinical trials altering poststroke immune responses and preventing infections.
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July 2010

Relationship between C-reactive protein and early activation of leukocytes indicated by leukocyte antisedimentation rate (LAR) in patients with acute cerebrovascular events.

Clin Hemorheol Microcirc 2010 ;44(3):183-92

Department of Anaesthesiology and Intensive Therapy, University of Pecs, Pecs, Hungary.

The purpose of this study was to determine the relationship between high-sensitive C-reactive protein (hsCRP) and leukocyte antisedimentation rate (LAR) as a specific test to detect early activation of leukocytes providing the first line of defence against infections in ischemic stroke. In 49 patients with acute ischemic events and 61 healthy subjects (HS), we examined LAR, astroglia specific S100B indicating the extent of brain tissue damage and hsCRP within 6 hours, as well as 24 and 72 hours after onset of symptoms. Serum levels of hsCRP on admission was significantly higher in patients with acute ischemic stroke (AIS) compared to HS and were higher in patients with recurrent to first ever ischemic stroke. Increased basal levels of hsCRP also correlated with severity of stroke and extent of infarct reflected by S100B levels in sera, but did not correlate with post-stroke infections. However, a higher rate of infection was observed among patients, in whom hsCRP was elevated at 72 hours but LAR did not increase. Therefore, such late elevation of hsCRP may indicate pre-clinical infections due to deficient leukocyte activation. Simple tests like LAR and hsCRP may help in predicting outcome and high risk of infectious complications.
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http://dx.doi.org/10.3233/CH-2010-1273DOI Listing
September 2010
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