ABSTRACT
Background: Leber Hereditary Optic Neuropathy (LHON) is the most common inherited mitochondrial disease characterized by bilateral, painless, subacute visual loss with a peak age of onset in the second to third decade. Historically, LHON was thought to be exclusively maternally inherited due to mutations in mitochondrial DNA (mtDNA); however, recent studies have identified an autosomal recessive form of LHON (arLHON) caused by point mutations in the nuclear gene, DNAJC30. Case Presentations: In this study, we report the cases of three Eastern European individuals presenting with bilateral painless visual loss, one of whom was also exhibiting motor symptoms. After a several-year-long diagnostic journey, all three patients were found to carry the homozygous c.152A>G (p.Tyr51Cys) mutation in DNAJC30. This has been identified as the most common arLHON pathogenic variant and has been shown to exhibit a significant founder effect amongst Eastern European individuals. Conclusion: This finding adds to the growing cohort of patients with arLHON and demonstrates the importance of DNAJC30 screening in patients with molecularly undiagnosed LHON, particularly in Eastern European individuals. It is of heightened translational significance as patients diagnosed with arLHON exhibit a better prognosis and response to therapeutic treatment with the co-enzyme Q10 analog idebenone.
ABSTRACT
Multiple sclerosis (MS) may impact quality of life, careers and family plans of the affected individuals. The current treatments with disease modifying therapies aim to prevent people with MS (pwMS) from disability accumulation and progression. Different countries have different reimbursement policies resulting in inequalities in patient care among geographical regions. Access to anti-CD20 therapies for relapsing MS is restricted in Hungary because therapy of individual cases only is reimbursed. In the light of the latest research and national guidelines, 17 Hungarian MS experts agreed on 8 recommendations regarding relapsing pwMS using the Delphi round method. Strong agreement (> 80%) was achieved in all except one recommendation after three rounds, which generated a fourth Delphi round. The experts agreed on treatment initiation, switch, follow-up and discontinuation, as well as on special issues such as pregnancy, lactation, elderly population, and vaccination. Well-defined national consensus protocols may facilitate dialogue between policymakers and healthcare professionals and thus contribute to better patient care in the long run.
Subject(s)
Multiple Sclerosis , Aged , Pregnancy , Female , Humans , Hungary , Quality of Life , ConsensusABSTRACT
Összefoglaló. Bevezetés: Mivel hazánkban a sclerosis multiplex gyakoriságáról, valamint életkori és nemi jellegzetességeirol az elmúlt évtizedekben - egészen 2020-ig - csak regionális jellegu felmérések készültek egy-egy centrum betegforgalma alapján, az újonnan diagnosztizált és már ismert betegek országos koreloszlásáról és annak idobeli változásairól nincsenek ismereteink. Célkituzés: Jelen munkánkban több mint 14 000 beteg adatainak elemzésével a prevalens és incidens betegek koreloszlásának változását vizsgáljuk 2004-2016 során, és eredményeinket összevetjük az elmúlt évtizedekben közölt hazai adatokkal. Módszer: Munkacsoportunk az egészségbiztosítási pénztár anonimizált NEUROHUN adatbázisát elemezte, amely tartalmazza a 2004 és 2016 között az összes hazai, államilag finanszírozott, a fekvo- és járóbeteg-szakellátásból neurológiai diagnózissal jelentett esetet. A sclerosis multiplex BNO-kódjának elofordulása alapján korábban létrehoztuk a betegség adminisztratív definícióját, és megbecsültük a sclerosis multiplex országos prevalenciáját és incidenciáját. Eredmények: A prevalens betegek átlagéletkora 2015-ben 47,9 év, ugyanebben az évben az incidens betegek átlagéletkora 37,4 év volt. Vizsgálatunk szerint a prevalens betegek átlagéletkora szignifikánsan - évente egyötöd-egyharmad évvel (p<0,001) - emelkedik, mégpedig a nok esetében nagyobb mértékben. A nok átlagosan fél évvel idosebbek, mint a férfi páciensek (szignifikáns különbség: p = 0,002). A prevalens betegekben a legnépesebb korosztály az ötvenévesek felol a fiatalabb, 35-40 éves korosztály felé mozdul. Az incidens betegek átlagéletkora lassan, de szignifikánsan - évente átlagosan egyharmad évvel (p<0,001) - csökken. Következtetés: Eredményeink szerint az újonnan diagnosztizált sclerosis multiplexes páciensek átlagosan egyre fiatalabbak, és a prevalens betegek között is egyre fiatalabb korosztályok a legnépesebbek, de a javuló túlélés és a hosszabb élettartam miatt a prevalens betegek átlagéletkora összességében valószínuleg fokozatosan emelkedik. Orv Hetil. 2021; 162(19): 746-753. INTRODUCTION: The nationwide age and gender distribution of newly diagnosed and prevalent multiple sclerosis patients has been unknown in Hungary, as until 2020 only regional studies had been reported about the frequency and age characteristics of subjects with multiple sclerosis, based on single-center patient registries. OBJECTIVE: In the present study with the analysis of over 14 000 patients, we describe the changes in age distribution of prevalent and incident subjects between 2004 and 2016 and compare our results with the data published on the subject during the last decades in Hungary. METHOD: We have analyzed the pseudonymized NEUROHUN database provided by the single-payer National Health Insurance Fund, that contains each claim submitted by public hospitals and outpatient services for neurologic diseases between 2004 and 2016. Using the ICD10-code of multiple sclerosis, we have previously established the administrative definition of the illness and estimated its prevalence and incidence in the country. RESULTS: The mean age of prevalent patients was 47.9 years in 2015, whereas in the same year the mean age of incident cases was 37.4 years. The average age of prevalent patients shows a significant rise - with an annual increase of one fifth-one third year (p<0.001) - with a more pronounced increase among women. The age of women is higher by half a year (p = 0.002). The most populous age groups among prevalent subjects shift from the fifties towards the younger generations between 35-40 years of age. The average age of incident subjects slowly, but significantly decreases, with a mean annual decrease of about one third year (p<0.001). CONCLUSION: Our results suggest that though new patients are younger year-by-year and the most populous age groups are also younger, altogether the average age of prevalent subjects continuously increases, probably due to the longer survival and lifespan of patients with multiple sclerosis. Orv Hetil. 2021; 162(19): 746-753.
Subject(s)
Multiple Sclerosis , Sex Characteristics , Adult , Ambulatory Care , Female , Humans , Hungary , Incidence , Middle Aged , Multiple Sclerosis/epidemiologyABSTRACT
OBJECTIVES: As there were only regional studies in Hungary about the prevalence of multiple sclerosis (MS), we aimed to estimate its epidemiological features using data of Hungary's single-payer health insurance system. METHODS: Pseudonymized database of claims reported by hospitals and outpatient services between 2004-2016 was analyzed and linked with an independent database of outpatient pharmacy refills between 2010-2016. We established an administrative case definition of MS and validated it on medical records of 309 consecutive patients. A subject was defined as MS-patient if received MS diagnosis (International Classification of Diseases, 10th edition, code G35) on three or more occasions at least in 2 calendar years and at least once documented by a neurologist. Patients were counted as incident cases in the year of the first submitted claim for MS. We allowed a 6-year-long run-in period, so only data between 2010-2015 are discussed. RESULTS: Sensitivity of the administrative case definition turned out to be 99%, while specificity was >99%. Crude prevalence of MS has increased from 109.3/100,000 in 2010 to 130.8/100,000 in 2015 (p-value = 0.000003). Crude incidence declined from 7.1/100,000 (2010) to 5.4/100,000 (2015) (p-value = 0.018). Direct standardization - based on European standard population and results of nationwide Hungarian census of 2011 - revealed that age standardized prevalence was 105.2/100,000 (2010), which has grown to 127.2/100,000 (2015) (p-value = 0.000001). Age standardized incidence rate declined from 6.7/100,000 (2010) to 5.1/100,000 (2015) (p-value = 0.016). The ratio of MS-patients receiving ≥1 prescription for disease modifying treatment increased from 0.19 (2010) to 0.29 (2015) (p-value = 0.0051). The female/male ratio of prevalent cases remained 2.6. DISCUSSION: The prevalence of MS in Hungary is higher than previously reported, the incidence rate is moderate. The prevalence is rising, the incidence rate shows decline. The proportion of patients receiving disease modifying treatment grows but was still around 30% in 2015.
Subject(s)
Data Analysis , Delivery of Health Care/organization & administration , Multiple Sclerosis/epidemiology , Records , Age Factors , Algorithms , Female , Humans , Hungary/epidemiology , Incidence , Male , Multiple Sclerosis/diagnosis , Multiple Sclerosis/drug therapy , Prevalence , Reproducibility of ResultsABSTRACT
Inflammation contributes to the pathogenesis of low back pain and sciatica. Growing evidence suggests that elevated levels of some inflammatory biomarkers are associated with these conditions. Much of the research evaluating the association between pro- and anti-inflammatory cytokines, chemokines, other regulatory molecules, and low back pain and sciatica, focused on patients with chronic low back pain, while fewer studies addressed the issue of detectable biomarkers in the acute phase. Previous studies suggest that pro-inflammatory cytokines such as TNF-α, IL-6, and IL-8 and anti-inflammatory IL-4 and IL-10 play an important role in the inflammatory response following intervertebral disc herniation. According to the approach of personalized medicine it is important to identify subsets of patients within the acute patient group regarding etiology, prognosis and treatment. In addition, if we can identify subgroups based on levels of pro-inflammatory biomarkers, where inflammation may be the leading cause of pain, we assume that this subgroup would likely be effectively treated with anti-inflammatory medication. The efficacy of TNF-α inhibitors and IL-6 inhibitors in treating low back pain and sciatica has already been tested in clinical trials, but further studies are required. Overall, identification of circulating biomarkers of acute low back pain and sciatica may assist in refining personalized diagnosis and treatment. Further research is needed to evaluate the role of inflammation in acute low back pain and sciatica, to identify what methods are appropriate for evaluation in clinical practice, and whether there are biomarkers of prognostic value in these patients. Orv Hetil. 2020; 161(13): 483-490.
Subject(s)
Cytokines/blood , Intervertebral Disc Displacement/blood , Low Back Pain/blood , Sciatica/blood , Biomarkers/blood , Humans , Intervertebral Disc Degeneration/blood , Intervertebral Disc Displacement/immunology , Low Back Pain/etiology , Sciatica/immunologyABSTRACT
BACKGROUND: Aquaporin-4-IgG positive (AQP4-IgG+) Neuromyelitis Optica Spectrum Disorder (NMOSD) is an uncommon central nervous system autoimmune disorder. Disease outcomes in AQP4-IgG+NMOSD are typically measured by relapse rate and disability. Using the MSBase, a multi-centre international registry, we aimed to examine the impact immunosuppressive therapies and patient characteristics as predictors of disease outcome measures in AQP4-IgG+NMOSD. METHOD: This MSBase cohort study of AQP4-IgG+NMOSD patients examined modifiers of relapse in a multivariable proportional hazards model and expanded disability status score (EDSS) using a mixed effects model. RESULTS: 206 AQP4-IgG+ patients were included (median follow-up 3.7 years). Age (hazard ratio [HR] = 0.82 per decade, p = 0.001), brainstem onset (HR = 0.45, p = 0.009), azathioprine (HR = 0.46, p<0.001) and mycophenolate mofetil (HR = 0.09, p = 0.012) were associated with a reduced risk of relapse. A greater EDSS was associated with age (ß = 0.45 (per decade), p<0.001) and disease duration (ß = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (ß = -0.48, p<0.001), mycophenolate mofetil (ß = -0.69, p = 0.04) and rituximab (ß = -0.35, p = 0.024). INTERPRETATION: This study has demonstrated that azathioprine and mycophenolate mofetil reduce the risk of relapses and disability progression is modified by azathioprine, mycophenolate mofetil and rituximab. Age and disease duration were the only patient characteristics that modified the risk of relapse and disability in our cohort.
Subject(s)
Aquaporin 4/immunology , Disease Progression , Immunologic Factors/pharmacology , Neuromyelitis Optica , Outcome Assessment, Health Care , Registries , Severity of Illness Index , Adult , Age Factors , Azathioprine/pharmacology , Female , Follow-Up Studies , Humans , Immunoglobulin G , Male , Middle Aged , Mycophenolic Acid/pharmacology , Neuromyelitis Optica/drug therapy , Neuromyelitis Optica/immunology , Neuromyelitis Optica/physiopathology , Recurrence , Rituximab/pharmacology , Time FactorsABSTRACT
BACKGROUND: The definition of benign multiple sclerosis (BMS) is still debated. It is mainly based on physical status, however, there is an attempt to involve cognitive functioning or paraclinical factors in order to avoid unnecessary long-term treatment with disease-modifying therapies and to identify these subjects in the early stages of the disease. Therefore the aim of our two-year follow-up study was to investigate the pattern of cognitive functioning and depression in patients with BMS compared to treated relapsing-remitting MS (RRMS) patients and healthy controls. METHODS: A group of 22 BMS patients was tested against matched RRMS patients and healthy controls. All individuals underwent neuropsychological evaluation exploring mood and the cognitive domains most frequently impaired in MS. MS patients were retested at two-year follow-up. RESULTS: In terms of cognitive functions there were no differences between BMS and RRMS patients either at baseline or at two-year follow-up. Compared to healthy controls BMS patients showed poorer performance in long-term visuo-spatial memory and information processing speed, whereas, complex attention, working memory, long-term verbal memory - despite slower verbal learning - and executive function were found to be intact. RRMS patients showed significant difference in complex attention, long-term visual memory and information processing speed. Cognitive impairment differed in the patient groups in terms of severity. Both patient groups were depressed compared to controls, but significant differences were found only between BMS and healthy individuals. CONCLUSION: The results of our study confirm that cognitive functions and mood can be affected in MS independent of disease course and disease modifying treatment. The "benign" label should be treated as only a reference to physical status and non-motor symptoms should be routinely monitored. Without receiving therapy it is an existing entity with longstanding minimal disability.
Subject(s)
Attention/physiology , Cognition/physiology , Cognitive Dysfunction/etiology , Executive Function/physiology , Memory, Short-Term/physiology , Multiple Sclerosis/psychology , Adult , Affect/physiology , Cognitive Dysfunction/diagnosis , Depression/etiology , Depression/psychology , Female , Follow-Up Studies , Humans , Male , Middle Aged , Multiple Sclerosis/complications , Multiple Sclerosis, Relapsing-Remitting/complications , Multiple Sclerosis, Relapsing-Remitting/psychology , Neuropsychological Tests , Reaction Time/physiology , Registries , Severity of Illness IndexABSTRACT
Vast amounts of data are created during routine patient care which are stored in unstructured digital and hardcopy formats in healthcare institutions. Analysis of large databases help to define the healthcare needs of the population and to organize healthcare services for specific diseases. As a model, we selected multiple sclerosis (MS), a disease with well-defined diagnostic criteria, a usually inpatient initial diagnosis, and a need for regular outpatient check-up. Using multiple sclerosis as an example, we set forth to screen and analyze international and Hungarian databases. In the framework of the initiation of the data lake system of Semmelweis University, we aim to define features of the data system needed for disease-specific databases for future applications. To determine essential data-entry criteria for such a database, we review the most important multiple sclerosis registries. We evaluate the type of registered data, structure of database, privacy issues, the availability and ways of application of the databases. Initially, the MS databases were created locally, aiming for better care of patients. As a further step, data were collected for scientific research by national and international co-operations. Disease-specific databases have become of high priority for national healthcare providers, and long-term information on a population ("real-world" data) is extremely important to assess the effectivity and safety of a treatment at the population level. Our analysis contributes to a project which focuses on the aspects of developing a data lake at a service provider level including clinical, diagnostic and digital healthcare departments of Semmelweis University, Budapest, Hungary. Orv Hetil. 2019; 160(4): 123-130.
Subject(s)
Data Collection/standards , Databases as Topic/standards , Multiple Sclerosis , Nervous System Diseases , Big Data , Data Collection/methods , Databases, Factual , Humans , Hungary , RegistriesABSTRACT
INTRODUCTION: Data during routine patient care are created in multiple digital and paper-based hardcopy systems, therefore their retrieval is cumbersome in the follow-up of patients. Multiple sclerosis is the most prevalent neurological disorder in the young age, with major consequences on health and socio-economic status. AIM: We set forth to create a user-friendly, detailed local database where it is easy to access, register and analyze data. Based on our experiences during building this registry, we develop the model of a modern type of database. METHOD: First we established a local registry in Excel, then data were transferred to the worldwide used iMed system. Separate pages were used to register basic data, follow-up visits, relapses, accompanying diseases, results of neuroimaging, cerebrospinal fluid, evoked response and other tests, pharmacological and non-pharmacological treatments. RESULTS: The database currently contains data of 316 patients. MRI was performed in 96%, cerebrospinal fluid examination in 45% of the patients. The rate of primary progressive disease at disease onset is 9%. Disease modifying treatments were applied in 82% of the patients. CONCLUSION: The traditional manual data entry and data export in PDF format is obsolete and time-consuming. The development of local disease-specific databases appropriate for clinical and research purposes requires continuous and mostly automatic data entry. In future local registries the establishment of uniform documentational language and structure, and automatic transfer of information among different digital systems are required. We present the model of such a registry, which is based on a healthcare data lake. Orv Hetil. 2019; 160(4): 131-137.
Subject(s)
Data Collection/standards , Databases as Topic/standards , Databases, Factual , Multiple Sclerosis , Patient Care/trends , Registries , Data Collection/methods , Databases, Factual/trends , Forecasting , Humans , HungaryABSTRACT
BACKGROUND: Alemtuzumab, an anti-CD52 antibody, is proven to be more efficacious than interferon beta-1a in the treatment of relapsing-remitting multiple sclerosis, but its efficacy relative to more potent immunotherapies is unknown. We compared the effectiveness of alemtuzumab with natalizumab, fingolimod, and interferon beta in patients with relapsing-remitting multiple sclerosis treated for up to 5 years. METHODS: In this international cohort study, we used data from propensity-matched patients with relapsing-remitting multiple sclerosis from the MSBase and six other cohorts. Longitudinal clinical data were obtained from 71 MSBase centres in 21 countries and from six non-MSBase centres in the UK and Germany between Nov 1, 2015, and June 30, 2016. Key inclusion criteria were a diagnosis of definite relapsing-remitting multiple sclerosis, exposure to one of the study therapies (alemtuzumab, interferon beta, fingolimod, or natalizumab), age 65 years or younger, Expanded Disability Status Scale (EDSS) score 6·5 or lower, and no more than 10 years since the first multiple sclerosis symptom. The primary endpoint was annualised relapse rate. The secondary endpoints were cumulative hazards of relapses, disability accumulation, and disability improvement events. We compared relapse rates with negative binomial models, and estimated cumulative hazards with conditional proportional hazards models. FINDINGS: Patients were treated between Aug 1, 1994, and June 30, 2016. The cohorts consisted of 189 patients given alemtuzumab, 2155 patients given interferon beta, 828 patients given fingolimod, and 1160 patients given natalizumab. Alemtuzumab was associated with a lower annualised relapse rate than interferon beta (0·19 [95% CI 0·14-0·23] vs 0·53 [0·46-0·61], p<0·0001) and fingolimod (0·15 [0·10-0·20] vs 0·34 [0·26-0·41], p<0·0001), and was associated with a similar annualised relapse rate as natalizumab (0·20 [0·14-0·26] vs 0·19 [0·15-0·23], p=0·78). For the disability outcomes, alemtuzumab was associated with similar probabilities of disability accumulation as interferon beta (hazard ratio [HR] 0·66 [95% CI 0·36-1·22], p=0·37), fingolimod (1·27 [0·60-2·70], p=0·67), and natalizumab (0·81 [0·47-1·39], p=0·60). Alemtuzumab was associated with similar probabilities of disability improvement as interferon beta (0·98 [0·65-1·49], p=0·93) and fingolimod (0·50 [0·25-1·01], p=0·18), and a lower probability of disability improvement than natalizumab (0·35 [0·20-0·59], p=0·0006). INTERPRETATION: Alemtuzumab and natalizumab seem to have similar effects on annualised relapse rates in relapsing-remitting multiple sclerosis. Alemtuzumab seems superior to fingolimod and interferon beta in mitigating relapse activity. Natalizumab seems superior to alemtuzumab in enabling recovery from disability. Both natalizumab and alemtuzumab seem highly effective and viable immunotherapies for multiple sclerosis. Treatment decisions between alemtuzumab and natalizumab should be primarily governed by their safety profiles. FUNDING: National Health and Medical Research Council, and the University of Melbourne.
Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Fingolimod Hydrochloride/therapeutic use , Immunologic Factors/therapeutic use , Interferon-beta/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Natalizumab/therapeutic use , Adult , Alemtuzumab , Cohort Studies , Databases, Bibliographic/statistics & numerical data , Disability Evaluation , Female , Humans , Male , Treatment Outcome , Young AdultABSTRACT
Multiple sclerosis is an autoimmune demyelinating disorder of the central nervous system. During the last two decades, numerous disease modifying drugs have been introduced for the treatment of the relapsing-remitting form of the disease. Since 2010, natalizumab (NTZ) treatment has been used as a second-line therapy for patients with breakthrough disease. In comparison to conventional immunomodulant drugs, NTZ has a more specific effect in that it prevents the entry of immune cells into the central nervous system without interfering with systemic immune response. The efficacy and the safety of NTZ have been confirmed by several studies. The most severe side-effect of NTZ is progressive multifocal leukoencephalopathy, which has been associated with an increased incidence in patients with anti-JCV antibody positivity, and in those who have been undergoing NTZ treatment for over two years and who have received prior immunosuppressive therapy. In the present study, our experience with natalizumab treatment of 37 patients at the Department of Neurology of Semmelweis University during the last 6 years is presented. We have observed a significant decrease of disease activity in our patients; in many cases the disease has become inactive both clinically (36/37) and radiologically (34/37). The patients' quality of life has improved significantly during the treatment. In accordance with the literature, we confirm that NTZ is a highly effective treatment in a carefully selected patient group, and can be administered without significant inconvenience to the patient.
Subject(s)
Immunologic Factors/therapeutic use , Multiple Sclerosis/therapy , Natalizumab/therapeutic use , Academic Medical Centers , Humans , Immunomodulation , Multiple Sclerosis/diagnostic imaging , Quality of Life , Treatment Outcome , UniversitiesABSTRACT
The subcutaneous peginterferon-b-1a is recently introduced in the therapy of relapsing-remitting multiplex sclerosis (RRMS) patients. Pegylation of IFN b-1a improved pharmacodynamic and pharmacokinetic properties, resulting in, increased biologic activity and a longer half-life. The efficacy of peginterferon-b-1a was proved by the ADVANCE study - a 2-year Phase 3, multicenter, randomized, double-blind study with a 1-year placebocontrolled period evaluating the efficacy and safety of subcutaneous peginterferon-b-1a administered every 2 or 4 weeks in patients with RRMS. Peginterferon-b-1a efficacy was maintained during the two years, with greater effects observed with every 2 week versus every 4 week dosing. Annualized relapse rate and confirmed disability progression was reduced comparing with patients on delayed treatment. Patients treated with continuous peginterferon-b-1a had fewer new or newly enlarging T2 lesions over 2 years than patients in the delayed treatment group. Adverse events were consistent with the known profiles of IFN b therapies in MS. The most commonly reported adverse events were injection site erythema, influenza-like illness. The less frequent administration is associated with fewer flu-like adverse events, which may improve patients' compliance and adherence. Peginter-feron-b-1a could be an effective and safe treatment option for RRMS patients.
Subject(s)
Immunologic Factors/therapeutic use , Interferon-beta/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/therapy , Polyethylene Glycols/therapeutic use , Clinical Trials as Topic , Humans , Immunologic Factors/adverse effects , Interferon-beta/adverse effects , Polyethylene Glycols/adverse effectsABSTRACT
BACKGROUND: Neuromyelitis optica (NMO)-systemic lupus erythematosus (SLE) association is a rare condition characterized by multiple autoantibodies. OBJECTIVE: To examine if, during the evolution of NMO, anti-AQP4 responses are part of polyclonal B cell activation, and if T cell responses contribute. METHODS: In 19 samples of six patients who developed NMO during SLE, we examined the correlation of AQP4-IgG1 and IgM with (i) anti-MOG IgG and IgM, (ii) anti-nuclear, anti-nucleosome and anti-dsDNA IgG antibodies, (iii) cytokines and chemokines in the serum and (iv) longitudinal relation to NMO relapses/remission. RESULTS: AQP4-IgG1 was present 1-2-5 years before the first NMO relapse. During relapse, AQP4-IgG1, ANA, anti-dsDNA and anti-nucleosome antibodies were elevated. Anti-MOG IgG/IgM and AQP4-IgM antibodies were not detected. AQP4-IgG1 antibodies correlated with concentration of anti-nucleosome, IFN-γ,interferon-gamma-induced CCL10/IP-10 and CCL17/TARC (p<0.05, respectively). CCL17/TARC correlated with levels of anti-nucleosome and anti-dsDNA (p<0.05, respectively). Compared to healthy subjects, concentration of IFN-γ and CCL17/TARC was higher in NMO/SLE (p<0.05). CONCLUSIONS: AQP4-IgG1 antibodies are present in the sera years before the first NMO attack in patients with SLE; elevation of anti-AQP4 is part of a polyclonal B cell response during NMO relapses; in spite of multiple autoantibodies in the serum, MOG antibodies were not present; Th1 responses accompany autoantibody responses in NMO/SLE.
Subject(s)
Aquaporin 4/immunology , Autoantibodies/blood , Cytokines/blood , Immunoglobulin G/blood , Immunoglobulin M/blood , Lupus Erythematosus, Systemic/immunology , Neuromyelitis Optica/immunology , Adolescent , Adult , B-Lymphocytes/immunology , B-Lymphocytes/metabolism , Biomarkers/blood , Child , Female , Humans , Immunosuppressive Agents/therapeutic use , Lupus Erythematosus, Systemic/blood , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Lymphocyte Activation , Middle Aged , Neuromyelitis Optica/blood , Neuromyelitis Optica/diagnosis , Neuromyelitis Optica/drug therapy , Preliminary Data , Recurrence , Remission Induction , Retrospective Studies , Th1 Cells/immunology , Th1 Cells/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism , Time Factors , Treatment Outcome , Young AdultABSTRACT
PURPOSE: To assess the differences in texture descriptors and optical properties of retinal tissue layers in patients with multiple sclerosis (MS) and to evaluate their usefulness in the detection of neurodegenerative changes using optical coherence tomography (OCT) image segmentation. PATIENTS AND METHODS: 38 patients with MS were examined using Stratus OCT. The raw macular OCT data were exported and processed using OCTRIMA software. The enrolled eyes were divided into two groups, based on the presence of optic neuritis (ON) in the history (MSON+ group, n = 36 and MSON- group, n = 31). Data of 29 eyes of 24 healthy subjects (H) were used as controls. A total of seven intraretinal layers were segmented and thickness as well as optical parameters such as contrast, fractal dimension, layer index and total reflectance were measured. Mixed-model ANOVA analysis was used for statistical comparisons. RESULTS: Significant thinning of the retinal nerve fiber layer (RNFL), ganglion cell/inner plexiform layer complex (GCL+IPL) and ganglion cell complex (GCC, RNFL+GCL+IPL) was observed between study groups in all comparisons. Significant difference was found in contrast in the RNFL, GCL+IPL, GCC, inner nuclear layer (INL) and outer plexiform layer when comparing MSON+ to the other groups. Higher fractal dimension values were observed in GCL+IPL and INL layers when comparing H vs. MSON+ groups. A significant difference was found in layer index in the RNFL, GCL+IPL and GCC layers in all comparisons. A significant difference was observed in total reflectance in the RNFL, GCL+IPL and GCC layers between the three examination groups. CONCLUSION: Texture and optical properties of the retinal tissue undergo pronounced changes in MS even without optic neuritis. Our results may help to further improve the diagnostic efficacy of OCT in MS and neurodegeneration.
Subject(s)
Multiple Sclerosis/pathology , Retina/pathology , Adult , Case-Control Studies , Female , Humans , Male , Tomography, Optical CoherenceABSTRACT
OBJECTIVES: Inflammatory demyelinating diseases of the CNS comprise a broad spectrum of diseases like neuromyelitis optica (NMO), NMO spectrum disorders (NMO-SD) and multiple sclerosis (MS). Despite clear classification criteria, differentiation can be difficult. We hypothesized that the urine proteome may differentiate NMO from MS. METHODS: The proteins in urine samples from anti-aquaporin 4 (AQP4) seropositive NMO/NMO-SD patients (n = 32), patients with MS (n = 46) and healthy subjects (HS, n = 31) were examined by quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) after trypsin digestion and iTRAQ labelling. Immunoglobulins (Ig) in the urine were validated by nephelometry in an independent cohort (n = 9-10 pr. groups). RESULTS: The analysis identified a total of 1112 different proteins of which 333 were shared by all 109 subjects. Cluster analysis revealed differences in the urine proteome of NMO/NMO-SD compared to HS and MS. Principal component analysis also suggested that the NMO/NMO-SD proteome profile was useful for classification. Multivariate regression analysis revealed a 3-protein profile for the NMO/NMO-SD versus HS discrimination, a 6-protein profile for NMO/NMO-SD versus MS discrimination and an 11-protein profile for MS versus HS discrimination. All protein panels yielded highly significant ROC curves (AUC in all cases >0.85, p≤0.0002). Nephelometry confirmed the presence of increased Ig-light chains in the urine of patients with NMO/NMO-SD. CONCLUSION: The urine proteome profile of patients with NMO/NMO-SD is different from MS and HS. This may reflect differences in the pathogenesis of NMO/NMO-SD versus MS and suggests that urine may be a potential source of biomarkers differentiating NMO/NMO-SD from MS.
Subject(s)
Multiple Sclerosis/urine , Neuromyelitis Optica/urine , Proteome/metabolism , Proteomics/methods , Adult , Aged , Case-Control Studies , Cluster Analysis , Demography , False Positive Reactions , Female , Humans , Logistic Models , Male , Middle Aged , Principal Component Analysis , Risk Factors , Young AdultABSTRACT
BACKGROUND: Multiple sclerosis (MS) is the most common neuroimmunological disease. In addition to its somatic symptoms, fatigue, mood disorder (depression) and cognitive impairment can be detected. Cognitive impairment significantly affects social relationships, work capacity, quality of life independently of disability. AIM: The aim of our research is to analyse the complex relationship between depression, manifestation of which occurs more often in MS compared to normal population, and cognitive functioning in multiple sclerosis. METHODS: Forty participants (sixteen men, twenty-four women) are MS patients of the Department of Neurology, Semmelweis University. Control group included forty-two age-, gender-, and education-matched subjects (sixteen men, twenty-six women). Patients were screened using MMSE; and verbal learning, visual information processing, attention, short-term and long-term memory were tested. Depression was also assessed. RESULTS: In multiple sclerosis learning, long-term verbal memory and short-term visuospatial memory were impaired compared to control group. Working memory, information processing and attention were found to be intact. Depression scores of MS patients were significantly higher than those of the normal population. Regarding the relationship between depression and cognitive impairment, negative correlation was found between mood and short-term visuospatial memory. CONCLUSION: Results of our research reflect the findings of clinical studies whereas short-term and long-term memory excluding working memory can be impaired in multiple sclerosis. Because of incidence of depression and fatigue and the important role of psychological factors in quality of life, more detailed analysis of the relationship between mood, fatigue and cognitive impairment would be required which is planned in the future.
Subject(s)
Cognition , Cognitive Dysfunction/etiology , Depression/etiology , Memory Disorders/etiology , Memory , Multiple Sclerosis/psychology , Adult , Affect , Aged , Attention , Case-Control Studies , Cognitive Dysfunction/psychology , Depression/psychology , Fatigue/etiology , Female , Humans , Male , Memory Disorders/psychology , Memory, Long-Term , Memory, Short-Term , Middle Aged , Neuropsychological Tests , Pattern Recognition, Visual , Quality of Life , Verbal LearningABSTRACT
OBJECTIVE: In patients suffering multiple sclerosis activity despite treatment with interferon ß or glatiramer acetate, clinicians often switch therapy to either natalizumab or fingolimod. However, no studies have directly compared the outcomes of switching to either of these agents. METHODS: Using MSBase, a large international, observational, prospectively acquired cohort study, we identified patients with relapsing-remitting multiple sclerosis experiencing relapses or disability progression within the 6 months immediately preceding switch to either natalizumab or fingolimod. Quasi-randomization with propensity score-based matching was used to select subpopulations with comparable baseline characteristics. Relapse and disability outcomes were compared in paired, pairwise-censored analyses. RESULTS: Of the 792 included patients, 578 patients were matched (natalizumab, n = 407; fingolimod, n = 171). Mean on-study follow-up was 12 months. The annualized relapse rates decreased from 1.5 to 0.2 on natalizumab and from 1.3 to 0.4 on fingolimod, with 50% relative postswitch difference in relapse hazard (p = 0.002). A 2.8 times higher rate of sustained disability regression was observed after the switch to natalizumab in comparison to fingolimod (p < 0.001). No difference in the rate of sustained disability progression events was observed between the groups. The change in overall disability burden (quantified as area under the disability-time curve) differed between natalizumab and fingolimod (-0.12 vs 0.04 per year, respectively, p < 0.001). INTERPRETATION: This study suggests that in active multiple sclerosis during treatment with injectable disease-modifying therapies, switching to natalizumab is more effective than switching to fingolimod in reducing relapse rate and short-term disability burden.
Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , Immunosuppressive Agents/pharmacology , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Propylene Glycols/pharmacology , Registries , Sphingosine/analogs & derivatives , Adult , Antibodies, Monoclonal, Humanized/administration & dosage , Disability Evaluation , Disease Progression , Female , Fingolimod Hydrochloride , Humans , Immunosuppressive Agents/administration & dosage , Male , Middle Aged , Natalizumab , Propylene Glycols/administration & dosage , Recurrence , Severity of Illness Index , Sphingosine/administration & dosage , Sphingosine/pharmacology , Treatment OutcomeABSTRACT
In relapsing-remitting multiple sclerosis, only parenteral immunomodulatory treatments existed for 15 years, until 2010. In recent years, novel disease-modifying agents became available with new mechanisms of action and oral application, which expanded therapeutic options. Thus, when making therapeutic decisions, more and new aspects should be considered, and the daily practice of patient management has been changed due to the different profile of possible side-effects. The authors review the mechanism of action, pharmacokinetics, studies regarding efficacy, side-effects of first- and second line oral disease-modifying treatments and provide practical guide of their everyday usage.
Subject(s)
Crotonates/administration & dosage , Dimethyl Fumarate/administration & dosage , Fingolimod Hydrochloride/administration & dosage , Immunosuppressive Agents/administration & dosage , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Toluidines/administration & dosage , Administration, Oral , Crotonates/pharmacology , Dimethyl Fumarate/pharmacology , Fingolimod Hydrochloride/pharmacology , Humans , Hydroxybutyrates , Immunosuppressive Agents/pharmacology , Multiple Sclerosis, Relapsing-Remitting/immunology , Nitriles , Toluidines/pharmacologyABSTRACT
The purpose of our study was to examine how the pathologic type of polyneuropathy affects nerve size as assessed by high-resolution ultrasonography with a 15 MHz transducer. Cross-sectional area (CSA) of the C5-C7 nerve roots and several upper and lower limb nerves at multiple sites was measured in 38 patients with acquired diffuse sensorimotor demyelinating or axonal polyneuropathy and in 34 healthy control subjects. Significant differences were found among the groups for all nerve and root segments: Both types of polyneuropathy are characterized by nerve enlargement in comparison to controls, but in different patterns. In demyelinating polyneuropathies, an additional degree of nerve thickening appears in proximal upper limb nerves and cervical nerve roots compared with axonal polyneuropathies. With respect to the other nerves, a similar degree of nerve enlargement was observed in both patient groups. These results highlight that ultrasonography may be a complementary tool in differentiating polyneuropathies.
Subject(s)
Arm/innervation , Leg/innervation , Polyneuropathies/diagnostic imaging , Spinal Nerve Roots/diagnostic imaging , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Polyneuropathies/pathology , Prospective Studies , Spinal Nerve Roots/pathology , Transducers , UltrasonographyABSTRACT
OBJECTIVE: To evaluate nerve size parameters measured by ultrasound in patients with ulnar neuropathy at the elbow (UNE) and to correlate them with the type of nerve lesion. METHODS: The largest cross sectional area (CSA(max)) of the ulnar nerve around the elbow and the cubital-to-humeral nerve area ratio (CHR) were measured in 50 elbows with UNE and in 87 elbows of 50 healthy subjects. CSA(max) and CHR were compared between controls and patients with predominantly demyelinative and axonal nerve involvement. Subgroups of patients with pure sensory and mixed sensorimotor axonal lesion were also compared. RESULTS: In patients with axonal nerve involvement, a significantly larger CSA(max) and CHR were found when compared to those with predominantly demyelinating nerve lesion; both groups differed significantly from healthy controls. CSA(max) values in patients with sensorimotor axonal lesion were significantly higher than in those with pure sensory axonal involvement. CONCLUSION: CSA(max) and CHR highly correlate with the type of nerve pathology in UNE, with a significantly larger nerve swelling seen in axonal lesions, as compared to demyelinating lesions. SIGNIFICANCE: In addition to helping in the localization of nerve lesion, ultrasonography may also reflect the type and degree of nerve lesion as assessed by electrophysiological means.