Publications by authors named "Magdolna Simo"

30 Publications

  • Page 1 of 1

Effect of Disease-Modifying Therapy on Disability in Relapsing-Remitting Multiple Sclerosis Over 15 Years.

Neurology 2021 02 28;96(5):e783-e797. Epub 2020 Dec 28.

From CORe (T.K., I.D., S.S., C.M.), Department of Medicine, University of Melbourne; MS Centre (T.K., I.D., S.S., C.M.), Department of Neurology, Royal Melbourne Hospital, Australia; Karolinska Institute (T.S.), Stockholm, Sweden; Department of Neuroscience (T.S., V.J., A.v.d.W., O.S., H.B.), Central Clinical School, Monash University, Melbourne; Burnet Institute (T.S.), Melbourne, Australia; Department of Neurology and Center of Clinical Neuroscience (D.H., E.K.H.), General University Hospital and Charles University in Prague, Czech Republic; Department of Basic Medical Sciences, Neuroscience and Sense Organs (M. Trojano), University of Bari, Italy; Hospital Universitario Virgen Macarena (G.I.), Sevilla, Spain; Department of Neuroscience, Imaging and Clinical Sciences (A.L.), University "G. d'Annunzio," Chieti; Department of Biomedical and Neuromotor Sciences (A.L.), University of Bologna, IRCCS Istituto delle Scienze Neurologiche di Bologna, Italy; Hopital Notre Dame (A.P., M.G., P.D.), Montreal; CHUM and Universite de Montreal (A.P., M.G., P.D.); CISSS Chaudière-Appalache (P.G.), Levis, Canada; Department of Neurology (V.J., A.v.d.W., O.S., H.B.), Alfred Hospital, Melbourne, Australia; Neuro Rive-Sud (F. Grand'Maison), Quebec, Canada; Department of Neuroscience (P.S., D.F.), Azienda Ospedaliera Universitaria, Modena, Italy; Isfahan University of Medical Sciences (V.S.), Isfahan, Iran; Amiri Hospital (R. Alroughani), Kuwait City, Kuwait; Zuyderland Ziekenhuis (R.H.), Sittard, the Netherlands; Medical Faculty (M. Terzi), 19 Mayis University, Samsun; KTU Medical Faculty Farabi Hospital (C.B.), Karadeniz Technical University, Trabzon, Turkey; School of Medicine and Public Health (J.L.-S.), University Newcastle; Department of Neurology (J.L.-S.), John Hunter Hospital, Newcastle, Australia; UOC Neurologia (E.P.), Azienda Sanitaria Unica Regionale Marche-AV3, Macerata, Italy; Cliniques Universitaires Saint-Luc (V.V.P.), Brussels, Belgium; University of Parma (F. Granella); C. Mondino National Neurological Institute (R.B.), Pavia; Azienda Ospedaliera di Rilievo Nazionale San Giuseppe Moscati Avellino (D.S.), Italy; Flinders University (M. Slee), Adelaide; Westmead Hospital (S.V.), Sydney, Australia; Nemocnice Jihlava (R. Ampapa), Czech Republic; University of Queensland (P.M.), Brisbane; Royal Brisbane and Women's Hospital (P.M.), Brisbane, Australia; Hospital Germans Trias i Pujol (C.R.-T.), Badalona, Spain; CSSS Saint-Jérôme (J.P.), Canada; Hospital Universitario Donostia (J.O.), Paseo de Begiristain, San Sebastián, Spain; Hospital Italiano (E.C.), Buenos Aires, Argentina; Brain and Mind Centre (M.B.), University of Sydney, Australia; INEBA-Institute of Neuroscience Buenos Aires (M.L.S.), Argentina; Hospital de Galdakao-Usansolo (J.L.S.-M.), Galdakao, Spain; Liverpool Hospital (S. Hodgkinson), Sydney, Australia; Jahn Ferenc Teaching Hospital (C.R.), Budapest, Hungary; Craigavon Area Hospital (S. Hughes), UK; Jewish General Hospital (F.M.), Montreal, Canada; Deakin University (C.S.), Geelong; Monash Medical Centre (E.B.), Melbourne, Australia; South East Trust (O.G.), Belfast, UK; Perron Institute (A.K.), University of Western Australia, Nedlands; Institute of Immunology and Infectious Diseases (A.K.), Murdoch University; Sir Charles Gairdner Hospital (A.K.), Perth, Australia; Department of Neurology (T.C.), Faculty of Medicine, University of Debrecen, Hungary; Bombay Hospital Institute of Medical Sciences (B.S.), Mumbai, India; St Vincents Hospital (N.S.), Fitzroy, Melbourne, Australia; Veszprém Megyei Csolnoky Ferenc Kórház zrt (I.P.), Veszprem, Hungary; Royal Hobart Hospital (B.T.), Australia; Semmelweis University Budapest (M. Simo), Hungary; Central Military Emergency University Hospital (C.-A.S.), Bucharest; Titu Maiorescu University (C.-A.S.), Bucharest, Romania; BAZ County Hospital (A.S.), Miskolc, Hungary; and Box Hill Hospital (H.B.), Melbourne, Australia.

Objective: To test the hypothesis that immunotherapy prevents long-term disability in relapsing-remitting multiple sclerosis (MS), we modeled disability outcomes in 14,717 patients.

Methods: We studied patients from MSBase followed for ≥1 year, with ≥3 visits, ≥1 visit per year, and exposed to MS therapy, and a subset of patients with ≥15-year follow-up. Marginal structural models were used to compare the cumulative hazards of 12-month confirmed increase and decrease in disability, Expanded Disability Status Scale (EDSS) step 6, and the incidence of relapses between treated and untreated periods. Marginal structural models were continuously readjusted for patient age, sex, pregnancy, date, disease course, time from first symptom, prior relapse history, disability, and MRI activity.

Results: A total of 14,717 patients were studied. During the treated periods, patients were less likely to experience relapses (hazard ratio 0.60, 95% confidence interval [CI] 0.43-0.82, = 0.0016), worsening of disability (0.56, 0.38-0.82, = 0.0026), and progress to EDSS step 6 (0.33, 0.19-0.59, = 0.00019). Among 1,085 patients with ≥15-year follow-up, the treated patients were less likely to experience relapses (0.59, 0.50-0.70, = 10) and worsening of disability (0.81, 0.67-0.99, = 0.043).

Conclusion: Continued treatment with MS immunotherapies reduces disability accrual by 19%-44% (95% CI 1%-62%), the risk of need of a walking aid by 67% (95% CI 41%-81%), and the frequency of relapses by 40-41% (95% CI 18%-57%) over 15 years. This study provides evidence that disease-modifying therapies are effective in improving disability outcomes in relapsing-remitting MS over the long term.

Classification Of Evidence: This study provides Class IV evidence that, for patients with relapsing-remitting MS, long-term exposure to immunotherapy prevents neurologic disability.
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http://dx.doi.org/10.1212/WNL.0000000000011242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884998PMC
February 2021

Incidence and prevalence of multiple sclerosis in Hungary based on record linkage of nationwide multiple healthcare administrative data.

PLoS One 2020 27;15(7):e0236432. Epub 2020 Jul 27.

Department of Neurology, Semmelweis University, Budapest, Hungary.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236432PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7384662PMC
September 2020

[Serum biomarkers in acute low back pain and sciatica].

Orv Hetil 2020 Mar;161(13):483-490

Általános Orvostudományi Kar, Neurológiai Klinika,Semmelweis EgyetemBudapest, Balassa u. 6., 1083.

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.
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http://dx.doi.org/10.1556/650.2020.31665DOI Listing
March 2020

Clinical and therapeutic predictors of disease outcomes in AQP4-IgG+ neuromyelitis optica spectrum disorder.

Mult Scler Relat Disord 2020 Feb 25;38:101868. Epub 2019 Nov 25.

CORe, Department of Medicine, University of Melbourne, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. Electronic address:

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 (β = 0.45 (per decade), p<0.001) and disease duration (β = 0.07 per year, p<0.001). A slower increase in EDSS was associated with azathioprine (β = -0.48, p<0.001), mycophenolate mofetil (β = -0.69, p = 0.04) and rituximab (β = -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.
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http://dx.doi.org/10.1016/j.msard.2019.101868DOI Listing
February 2020

Neuropsychological characteristics of benign multiple sclerosis patients: A two-year matched cohort study.

Mult Scler Relat Disord 2019 Oct 27;35:150-155. Epub 2019 Jul 27.

Department of Neurology, Semmelweis University, Balassa J. u. 6., 1083 Budapest, Hungary.

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.
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http://dx.doi.org/10.1016/j.msard.2019.07.022DOI Listing
October 2019

[Multiple sclerosis in central Hungary: experiences and future possibilities of developing a local database].

Orv Hetil 2019 Jan;160(4):131-137

Neurológiai Klinika, Semmelweis Egyetem, Általános Orvostudományi Kar Budapest, Balassa u. 6., 1083.

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.
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http://dx.doi.org/10.1556/650.2019.31274DOI Listing
January 2019

[Databases in neurological diseases: overview of international examples in multiple sclerosis].

Orv Hetil 2019 Jan;160(4):123-130

Neurológiai Klinika, Semmelweis Egyetem, Általános Orvostudományi Kar Budapest, Balassa u. 6., 1083.

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.
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http://dx.doi.org/10.1556/650.2019.31273DOI Listing
January 2019

[Role of peginterferon-β-1a in the therapy of multiplex sclerosis].

Ideggyogy Sz 2017 Nov;70(11-12):365-368

Semmelweis Egyetem, Neurológiai Klinika, Budapest.

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.
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http://dx.doi.org/10.18071/isz.70.0365DOI Listing
November 2017

[Experience with natalizumab-treatment at Semmelweis University].

Ideggyogy Sz 2017 May;70(5-6):185-191

Semmelweis Egyetem, Neurológiai Klinika, Budapest.

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.
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http://dx.doi.org/10.18071/isz.70.0185DOI Listing
May 2017

Treatment effectiveness of alemtuzumab compared with natalizumab, fingolimod, and interferon beta in relapsing-remitting multiple sclerosis: a cohort study.

Lancet Neurol 2017 04 11;16(4):271-281. Epub 2017 Feb 11.

Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

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.
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http://dx.doi.org/10.1016/S1474-4422(17)30007-8DOI Listing
April 2017

[Oral disease-modifying agents in relapsing-remitting multiple sclerosis].

Neuropsychopharmacol Hung 2015 Dec;17(4):197-205

Semmelweis University Department of Neurology, Budapest, Hungary.

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.
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December 2015

Investigating Tissue Optical Properties and Texture Descriptors of the Retina in Patients with Multiple Sclerosis.

PLoS One 2015 30;10(11):e0143711. Epub 2015 Nov 30.

Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, Miami, Florida, United States of America.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143711PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4664388PMC
June 2016

Change in autoantibody and cytokine responses during the evolution of neuromyelitis optica in patients with systemic lupus erythematosus: A preliminary study.

Mult Scler 2016 08 29;22(9):1192-201. Epub 2015 Oct 29.

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

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.
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http://dx.doi.org/10.1177/1352458515613165DOI Listing
August 2016

The Urine Proteome Profile Is Different in Neuromyelitis Optica Compared to Multiple Sclerosis: A Clinical Proteome Study.

PLoS One 2015 13;10(10):e0139659. Epub 2015 Oct 13.

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

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0139659PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604198PMC
June 2016

[Association between depression and cognitive decline in sclerosis multiplex patients].

Neuropsychopharmacol Hung 2015 Mar;17(1):31-6

Semmelweis Egyetem, Neurológiai Klinika, Budapest, Hungary.

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.
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March 2015

Switch to natalizumab versus fingolimod in active relapsing-remitting multiple sclerosis.

Ann Neurol 2015 Mar 17;77(3):425-35. Epub 2015 Jan 17.

Department of Medicine, University of Melbourne, Melbourne, Australia; Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia.

Objective: In patients suffering multiple sclerosis activity despite treatment with interferon β 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.
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http://dx.doi.org/10.1002/ana.24339DOI Listing
March 2015

Different patterns of nerve enlargement in polyneuropathy subtypes as detected by ultrasonography.

Ultrasound Med Biol 2014 Jun 5;40(6):1138-45. Epub 2014 Mar 5.

Department of Neurology, Semmelweis University, Budapest, Hungary.

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.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2013.12.020DOI Listing
June 2014

Health status and costs of ambulatory patients with multiple sclerosis in Hungary.

Ideggyogy Sz 2012 Sep;65(9-10):316-24

Health Economics and Health Technology Assessment Research Centre, Corvinus University of Budapest.

Background And Purpose: Data on disease burden of multiple sclerosis from Eastern-Central Europe are very limited. Our aim was to explore the quality of life, resource utilisation and costs of ambulating patients with multiple sclerosis in Hungary.

Methods: Cross-sectional questionnaire survey was performed in two outpatient neurology centres in 2009. Clinical history, health care utilisation in the past 12 months were surveyed, the Expanded Disability Status Scale and the EQ-5D questionnaires were applied. Cost calculation was conducted from the societal perspective.

Results: Sixty-eight patients (female 70.6%) aged 38.0 (SD 9.1) with disease duration of 7.8 (SD 6.7) years were involved. Fifty-five (80.9%) had relapsing-remitting form and 52 (76.5%) were taking immunomodulatory drug. The average scores were: Expanded Disability Status Scale 1.9 (SD 1.7), EQ-5D 0.67 (SD 0.28). Mean total cost amounted to 10 902 Euros/patient/year (direct medical 67%, direct nonmedical 13%, indirect costs 20%). Drugs, disability pension and informal care were the highest cost items. Costs of mild (Expanded Disability Status Scale 0-3.5) and moderate (Expanded Disability Status Scale 4.0-6.5) disease were 9 218 and 17 634 Euros/patient/year respectively (p<0.01), that is lower than results from Western European countries.

Conclusion: Our study provides current inputs for policy making and contributes to understanding variation of cost-of-illness of multiple sclerosis in Europe.
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September 2012

Ultrasonography of ulnar neuropathy at the elbow: axonal involvement leads to greater nerve swelling than demyelinating nerve lesion.

Clin Neurophysiol 2013 Mar 12;124(3):619-25. Epub 2012 Oct 12.

Department of Neurology, Semmelweis University, Budapest, Hungary.

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.
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http://dx.doi.org/10.1016/j.clinph.2012.08.027DOI Listing
March 2013

Ultrasonography of MADSAM neuropathy: focal nerve enlargements at sites of existing and resolved conduction blocks.

Neuromuscul Disord 2012 Jul 16;22(7):627-31. Epub 2012 Apr 16.

Dept. of Neurology, Semmelweis University, Budapest, Hungary.

Using the emerging technique of peripheral nerve ultrasonography, multiple focal nerve swellings corresponding to sites of existing conduction blocks have been described in demyelinating polyneuropathies. We report two cases of multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). In the first, multiple focal nerve enlargements were detected by ultrasound at sites of previous conduction blocks, well after complete clinical and electrophysiological resolution. In the second case, existing proximal conduction blocks could be localized by ultrasound. Our cases highlight the importance of nerve ultrasound in identifying conduction blocks and demonstrate that ultrasonographic morphological changes may outlast functional recovery in demyelinating neuropathies.
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http://dx.doi.org/10.1016/j.nmd.2012.03.005DOI Listing
July 2012

In vivo evaluation of retinal neurodegeneration in patients with multiple sclerosis.

PLoS One 2012 26;7(1):e30922. Epub 2012 Jan 26.

Department of Ophthalmology, Semmelweis University, Budapest, Hungary.

Objective: To evaluate macular morphology in the eyes of patients with multiple sclerosis (MS) with or without optic neuritis (ON) in previous history.

Methods: Optical coherence tomography (OCT) examination was performed in thirty-nine patients with MS and in thirty-three healthy subjects. The raw macular OCT data were processed using OCTRIMA software. The circumpapillary retinal nerve fiber layer (RNFL) thickness and the weighted mean thickness of the total retina and 6 intraretinal layers were obtained for each eye. The eyes of MS patients were divided into a group of 39 ON-affected eyes, and into a group of 34 eyes with no history of ON for the statistical analyses. Receiver operating characteristic (ROC) curves were constructed to determine which parameter can discriminate best between the non-affected group and controls.

Results: The circumpapillary RNFL thickness was significantly decreased in the non-affected eyes compared to controls group only in the temporal quadrant (p = 0.001) while it was decreased in the affected eyes of the MS patients in all quadrants compared to the non-affected eyes (p<0.05 in each comparison). The thickness of the total retina, RNFL, ganglion cell layer and inner plexiform layer complex (GCL+IPL) and ganglion cell complex (GCC, comprising the RNFL and GCL+IPL) in the macula was significantly decreased in the non-affected eyes compared to controls (p<0.05 for each comparison) and in the ON-affected eyes compared to the non-affected eyes (p<0.001 for each comparison). The largest area under the ROC curve (0.892) was obtained for the weighted mean thickness of the GCC. The EDSS score showed the strongest correlation with the GCL+IPL and GCC thickness (p = 0.007, r = 0.43 for both variables).

Conclusions: Thinning of the inner retinal layers is present in eyes of MS patients regardless of previous ON. Macular OCT image segmentation might provide a better insight into the pathology of neuronal loss and could therefore play an important role in the diagnosis and follow-up of patients with MS.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0030922PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3266905PMC
June 2012

Nerve fiber layer and macular thinning measured with different imaging methods during the course of acute optic neuritis.

Eur J Ophthalmol 2011 Jul-Aug;21(4):473-83

Department of Ophthalmology, Semmelweis University, Budapest, Hungary.

Purpose: To compare retinal nerve fiber layer thickness (RNFLT) and inner macula thickness changes measured with Fourier-domain optical coherence tomography (FD-OCT) and scanning laser polarimetry during the course of acute optic neuritis (ON).

Methods: Nine eyes of 7 consecutive patients with multiple sclerosis (MS) were prospectively imaged from the onset of ON for 6 to 12 months. Nine healthy eyes were imaged for 12 to 19 months.

Results: Retinal nerve fiber layer thickness measured with FD-OCT initially increased in all eyes with diffuse optic disc edema. Inner macula thickness and polarimetric RNFLT decreased already in the acute phase, in all eyes. All parameters stabilized at 2 to 5 months. The relative structural loss was different with the different methods. Poor image quality with polarimetry occurred in 2 eyes in the acute phase of ON. In the control eyes all parameters were stable.

Conclusions: Change of RNFLT and macular thickness during the course of acute ON in MS strongly depends on the method used for the measurement. Inner macula thickness, measured with FD-OCT, was especially useful for the follow-up, since it was not influenced by initial disc edema and had consistently high image quality.
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http://dx.doi.org/10.5301/EJO.2010.5844DOI Listing
March 2012

[Devic syndrome--case report, current principles of diagnosis and therapy].

Ideggyogy Sz 2010 Sep;63(9-10):320-6

Semmelweis Egyetem, Neurológiai Klinika, Budapest.

Neuromyelitis optica (NMO, Devic-syndrome) is a rare, relapsing autoimmune disease of the central nervous system, which is distinguished from other demyelinating disorders by a recently identified, specific autoantibody. By demonstrating the anti-aquaporin-4 IgG in the serum, a heterogenous group of syndromes can be defined, called NMO-spectrum. In the future, optical coherence tomography may support this diagnosis besides the clinical features, imaging examinations and presence of serum antibody. Early recognition and treatment can improve clinical outcome even in serious condition. Long-term immunosuppressive therapy is advised to prevent further relapses and to stabilize or improve clinical status. Hereby, we report a case of a 51-year-old woman, under treatment for one and a half years. We summarize the current knowledge about the pathomechanism, diagnostic strategy and therapy of neuromyelitis optica. We review recent findings and the diagnostic value of a new, non-invasive ophtalmological examination, the optical coherence tomography. According to the first results, this method may be helpful in the early differential diagnosis of optic neuritis.
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September 2010

[Therapy of multiple sclerosis].

Authors:
Magdolna Simó

Neuropsychopharmacol Hung 2009 Mar;11(1):23-6

Semmelweis Egyetem, Neurológiai Klinika, Budapest.

Multiple sclerosis (MS) is one of the most frequent neuroimmunological disorders of the central nervous system. It is a multifactorial disease with possible causes including genetic and environmental factors. MS is characterized in essence by an autoimmune inflammation in the central nervous system, resulting in the damage of the myelin sheath and the axons. There are four pathological subtypes of the disease. Its clinical course can either be of the relapsing-remitting or primary and secondary progressive type. All structures of the central nervous system may be involved, but the longest tracts are affected the most often. According to the revised McDonald criteria, the diagnosis of MS is based on the clinical course and the MRI findings. Its therapy can be divided into the acute treatment of relapses, symptomatic relief and long-term immunomodulatory treatment. With respect to differential diagnosis, it is of special concern to distinguish between MS and neuromyelitis optica, as early diagnosis and appropriate treatment of the latter may prevent the development of severe residual symptoms associated with this disease.
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March 2009

Predictive role of evoked potential examinations in patients with clinically isolated optic neuritis in light of the revised McDonald criteria.

Mult Scler 2008 May 21;14(4):472-8. Epub 2008 Jan 21.

Department of Neurology, Semmelweis University, Balassa u. 6, 1083 Budapest, Hungary.

To analyse the sensitivity and role of somatosensory and motor evoked potentials (EP) in patients with a first episode of clinically isolated optic neuritis (ON) in predicting the development and course of multiple sclerosis (MS), 27 patients with ON underwent EP and magnetic resonance imaging (MRI) examinations at presentation. Follow-up MRI scans were also performed (mean: 20, range: 4-48 months). It was found that 2/27 patients did not fulfill the MRI (McDonald) and clinical criteria of MS upon follow-up and also had normal EP results. Abnormal EP results were found in 6/27 patients and all of them had follow-up MRI results fulfilling the revised McDonald criteria of MS; 4/6 patients in this group were also diagnosed as clinically definitive MS. The majority, 19/27 patients had normal EP results, but went on to develop MS based on follow-up MRI results and McDonald criteria. Of these patients, however, only 3/19 converted to clinically definitive MS as well. The baseline MRI was abnormal in similar proportions (4/6 and 12/19) in these last two groups of patients. Thus, abnormal EP examinations at the first episode of ON can be considered as a predictive factor only for the earlier clinical conversion to MS - in this respect, however, being more sensitive than the initial MRI - and as such they may contribute to the delineation of the patient group who may benefit from early immunomodulatory treatment. They do not however have a predictive value for the development of MS itself as diagnosed by the McDonald criteria.
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http://dx.doi.org/10.1177/1352458507085061DOI Listing
May 2008

[Role of motor evoked potentials in the diagnosis of myelopathy associated with cervical spondylosis].

Ideggyogy Sz 2003 Jan;56(1-2):51-7

Semmelweis Egyetem, Altalános Orvostudományi Kar, Neurológiai Klinika, H-1083 Budapest, Balassa u. 6.

Introduction: Motor evoked potential (MEP) is the only method that is able to assess the function of the corticospinal tract in various neurological conditions, such as myelopathies. Myelopathy associated with cervical spondylosis, especially at an early stage, has often slight and non-specific clinical signs, pointing to the importance of the electrophysiological assessment of the spinal cord. The authors' aim was to investigate the sensitivity of MEP examination in the detection of myelopathy secondary to cervical spondylosis.

Patients And Methods: Patients were classified into three groups according to clinical signs and symptoms: Group I includes patients who have cervical spondylosis as demonstrated by MRI (narrowing of the spinal canal, discal herniation, spinal cord compression) but no complaints or signs suggestive of myelopathy.

Results: In Group II patients had minor, non-specific complaints, such as paraesthesia of the legs and gait disturbance raising the possibility of myelopathy, but neurological examination revealed no pyramidal signs. In Group III patients had pyramidal signs as well. In Group I corticospinal function was normal in all patients, as assessed by MEP examination. In Group II all patients had prolonged central motor conduction time or absent responses to cortical stimulation. Likewise, in Group III MEP revealed abnormal corticospinal function in all patients but one.

Conclusions: In summary, MEP proved sensitive in the detection of corticospinal dysfunction in myelopathy associated with cervical spondylosis at a stage when clinical signs of pyramidal lesion are not yet present and patients have only minor complaints. On the other hand, if patients are completely symptom free with regard to myelopathy, MEP is also unlikely to disclose corticospinal dysfunction. If pyramidal lesion is evident already by clinical examination, MEP provides no further help. 'False-negative' results are also possible.
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January 2003

Primary intramedullary glioblastoma multiforme of the spinal cord: report of eight cases.

Ideggyogy Sz 2003 Jan;56(1-2):28-32

Országos Idegsebészeti Tudományos Intézet, 1145 Budapest, Amerikai út 57.

Primary glioblastoma multiforme located intramedullary in the spinal cord is a very rare entity. The authors report eight cases and discuss the clinical features, the possibility of diagnosis, combined treatment and pathomorphological signs focusing on the relevant literature and their experience.
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January 2003

[Role of transcranial magnetic stimulation in clinical diagnosis: facial nerve neurography].

Ideggyogy Sz 2002 Nov;55(11-12):356-67

Semmelweis Egyetem, Altalános Orvostudományi Kar, Neurológiai Klinika H-1083 Budapest, Balassa u. 6.

Facial nerve neurography involving magnetic stimulation techniques can be used to assess the intracranial segment of the facial nerve and the entire facial motor pathway, as opposed to the traditional neurography, involving only extracranial electric stimulation of the nerve. Both our own experience and data published in the literature underline the value of the method in localising facial nerve dysfunction and its role in clinical diagnosis. It is non-invasive and easy to perform. Canalicular hypoexcitability has proved to be the most useful and sensitive parameter, which indicates the dysfunction of the nerve between the brain stem and the facial canal. This is an electrophysiological finding which offers for the first time positive criteria for the diagnosis of Bell's palsy. The absence of canalicular hypoexcitability practically excludes the possibility of Bell's palsy. The technique is also able to demonstrate subclinical dysfunction of the nerve, which can be of considerable help in the etiological diagnosis of facial palsies. For example, in a situation where clinically unilateral facial weakness is observed, but facial nerve neurography demonstrates bilateral involvement, etiologies other than Bell's palsy are more likely, such as Lyme's disease, Guillain-Barré syndrome, meningeal affections etc. Furthermore, the technique differentiates reliably between peripheral facial nerve lesion involving the segment in the brain stem or the segment after leaving the brainstem.
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November 2002

[Role of transcranial magnetic stimulation in clinical diagnosis: motor-evoked potential (MEP)].

Ideggyogy Sz 2002 Sep;55(9-10):292-302

Semmelweis Egyetem, Altalános Orvosi Kar, Neurológiai Klinika, Budapest.

Transcranial magnetic stimulation allows painless, non-invasive stimulation, neurophysiological evaluation of nervous structure covered by bone or difficult to access for other reasons. In the clinical setting the technique is mainly used for the investigation of the corticospinal tract (motor evoked potential: MEP). Based upon our experience with patients examined over the course of four years, we have attempted to highlight the clinical situations, where diagnostic help is provided by this technique. MEP in general has proved to be a sensitive and reliable examination. Its significance is apparent mainly in situations where clinical signs of corticospinal tract dysfunction are not evident, or they are masked by lower motoneurone involvement, and where neuroimaging techniques are not informative. The demonstration of subclinical corticospinal lesion is often essential to establish the diagnosis in multiple sclerosis and amyotrophic lateral sclerosis. The technique however received little attention so far with respect to its role in the diagnosis of various spinal cord disorders, and in the demonstration of intact corticospinal function in case of weakness, psychogenic in origin. We have endeavored to provide further evidence in support of this, and thereby advocating a wider clinical application of the technique.
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September 2002