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Background: Cladribine is an oral disease-modifying drug authorized by the European Medicine Agency for the treatment of highly active relapsing multiple sclerosis (MS)., Objectives: To provide real-world evidence of cladribine's effectiveness and safety in people with MS (pwMS)., Methods: A retrospective observational multi-center, multi-national study of pwMS who were started on cladribine tablets in ten centers from five European countries., Results: We identified 320 pwMS treated with cladribine tablets. The most common comorbidities were arterial hypertension and depression. Three patients had resolved hepatitis B infection, while eight had positive Quantiferon test prior to cladribine commencement. There were six pwMS who had malignant diseases, but all were non-active. During year 1, 91.6% pwMS did not have EDSS worsening, 86.9% were relapse-free and 72.9% did not have MRI activity. During the second year, 90.2% did not experience EDSS worsening, 86.5% were relapse-free and 75.5% did not have MRI activity. NEDA-3 was present in 58.0% pwMS in year 1 and in 54.2% in year 2. In a multivariable logistic regression model age positively predicted NEDA-3 in year 1. The most common adverse events were infections and skin-related adverse events. Lymphopenia was noted in 54.7% of pwMS at month 2 and in 35.0% at month 6. Two pwMS had a newly discovered malignant disease, one breast cancer, and one melanoma, during the first year of treatment., Conclusion: Our real-world data on the effectiveness and safety of cladribine tablets are comparable to the pivotal study and other real-world data with no new safety signals., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Transorbital sonography (TOS) could be a swift and convenient method to detect the atrophy of the optic nerve, possibly providing a marker that might reflect other quantitative structural markers of multiple sclerosis (MS). Here we evaluate the utility of TOS as a complementary tool for assessing optic nerve atrophy, and investigate how TOS-derived measures correspond to volumetric brain markers in MS. We recruited 25 healthy controls (HC) and 45 patients with relapsing-remitting MS and performed B-mode ultrasonographic examination of the optic nerve. Patients additionally underwent MRI scans to obtain T1-weighted, FLAIR and STIR images. Optic nerve diameters (OND) were compared between HC, MS patients with and without history of optic neuritis (non-ON) using a mixed-effects ANOVA model. The relationship between within-subject-average OND and global and regional brain volumetric measures was investigated using FSL SIENAX, voxel-based morphometry and FSL FIRST. OND was significantly different between HC-MS (HC = 3.2 ± 0.4 mm, MS = 3 ± 0.4 mm; p < 0.019) and we found significant correlation between average OND and normalised whole brain (β = 0.42, p < 0.005), grey matter (β = 0.33, p < 0.035), white matter (β = 0.38, p < 0.012) and ventricular cerebrospinal fluid volume (β = - 0.36, p < 0.021) in the MS group. History of ON had no impact on the association between OND and volumetric data. In conclusion, OND is a promising surrogate marker in MS, that can be simply and reliably measured using TOS, and its derived measures correspond to brain volumetric measures. It should be further explored in larger and longitudinal studies., (© 2023. The Author(s).)

Background: In 2018 multiple sclerosis (MS) care unit (MSCU) recommendations were defined. Nevertheless, the information on MS care, and whether MS centres fulfil the international recommendation is limited. Thus our objectives were to assess whether centres meet the MSCU recommendations and gain a comprehensive overview of MS care in Central-Eastern European countries., Methods: A self-report questionnaire assessing aspects of the MSCU recommendations, disease-modifying therapy (DMT) and registry use and the patient number was assembled and sent to nine Central-Eastern European countries. Furthermore, one Danish and one German centre were contacted as a reference., Results: In 9/9 countries, MS care was pursued in centres by MS neurologists and MS nurses. In Austria and the Czech Republic, management of MS was conducted under strict regulations displaying a referral centre system, fundamentally similar to but independent of the MSCU criteria. Several centres fulfilled all aspects of the MSCU criteria, while others had similar insufficiencies consisting of a speech therapist, continence, pain and spasticity specialist, neuro-ophthalmologist, and oto-neurologist. In 9/9 countries, DMTs were reimbursed. However, some centres did not provide every available DMT. A national registry was available in 4/9 countries with mandatory registry use only in Austria and the Czech Republic., Conclusion: In countries where MSCU recommendations are not fulfilled, a strictly regulated centre system similar to the Austrian and Czech model with a registry-based quality control might ensure appropriate care for people with MS., Competing Interests: Declaration of Competing Interest The authors declare that no conflicting interests exist., (Copyright © 2022. Published by Elsevier B.V.)

Background and Purpose: Therapeutic strategy of relapse-remitting multiple sclerosis has changed significantly during the past decade. While earlier escalating therapy was widely applied, recently, in case of high disease activity, induction therapy has become available., Methods: In our study, we processed the data of our alemtuzumab treated patients from our register. Alte-ra-tions in relapse rate and MRI activity due to the treatment were determined. These data were compared in patients treated with alemtuzumab as an escalating and as an induction therapy. We noted the observed side effects., Results: The 49 patients observed in the study had undergone two cycles of alemtuzumab therapy. The drug was applied as an induction therapy in 9 cases. Average relapse rate during the two years was 1.4±1.0, which decreased to 0.1±0.3 in the two years following the therapy. The average EDSS before therapy was 2.7±2.2 in the induction therapy group and 2.7±1.7 in the escalating therapy group. After the treatment, this score decreased to 1.6±0.6 and 2.5±1.8 in the induction and the escalating therapy group, respectively. We found clinical and MRI progression in case of 4 patients. As regards to side effects, cytokine release was detected in 51.0% of the patients following the first cycle, and 24.5% of the patients following the second cycle of the therapy. Infection related to the therapy was observed in 28.6%, while autoimmune thyreoiditis was diagnosed in 18.3% of the patients., Conclusion: The tight follow-up of the treated patients and the precise documentation of the register enable the comparison of results yielded by placebo controlled clinical studies with daily practice, as well as to gain information on the benefits of induction therapy as a paradigm shift in treating MS patients.

Background: Wilson's disease is a hereditary disorder of copper metabolism resulting mainly in hepatic, neurological, and psychiatric symptoms. Multiple sclerosis (MS) is an immune-mediated demyelinating disease affecting the central nervous system (CNS). The co-occurrence of these two, although not unheard of in literature, is still considered to be very rare and can give rise to diagnostic difficulties. Also, comorbidity in MS highly influences quality of life and disease progression, which makes the timely diagnosis and treatment of these conditions essential., Case Presentation: The aim of this study is to present a patient exhibiting symptoms of both MS and Wilson's disease, as well as to conduct a detailed review of previously reported cases. The patient's neurological symptoms (sensory disorder) as well as MRI and CSF findings were characteristic for MS. The diagnosis of MS preceded that of Wilson's disease and was relatively mild in course. Currently, the patient receives cladribine as an immunomodulatory treatment after escalation from glatiramer acetate therapy. Apart from one episode of acute hepatic decompensation, during which transfusion, albumin supplementation and diuretic treatment was necessary, Wilson's disease manifested as chronic impairment of liver function. The diagnosis of Wilson's disease was established by the analysis of serum coeruloplasmin levels, histological examination and genetic findings. Continuous oral penicillamine therapy led to the slow normalization of hepatic function and significant amelioration of the patient's symptoms. Correlating with cases previously reported, the course of MS was relatively mild, and like in three out of four other known cases, the symptoms of Wilson's disease were mostly restricted to hepatic dysfunction., Conclusion: The case presented in our report is similar to those reported before. The co-occurrence of the two diseases seems to be more a coincidence than a sharing of common factors in their pathogenesis; however, they are considered to influence one another. Regarding rare co-occurrences such as this one, every new case is of high importance, as it enables a better evaluation and understanding of the clinical presentations that are more characteristic of these cases, thus aiding the estimation of disease course as well as possible therapeutic choices., (© 2022. The Author(s).)

Multiple sclerosis (MS) is the inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS) that affects approximately 2.8 million people worldwide. In the last decade, a new era was heralded in by a new phenotypic classification, a new diagnostic protocol and the first ever therapeutic guideline, making personalized medicine the aim of MS management. However, despite this great evolution, there are still many aspects of the disease that are unknown and need to be further researched. A hallmark of these research are molecular biomarkers that could help in the diagnosis, differential diagnosis, therapy and prognosis of the disease. Proteomics, a rapidly evolving discipline of molecular biology may fulfill this dire need for the discovery of molecular biomarkers. In this review, we aimed to give a comprehensive summary on the utility of proteomics in the field of MS research. We reviewed the published results of the method in case of the pathogenesis of the disease and for biomarkers of diagnosis, differential diagnosis, conversion of disease courses, disease activity, progression and immunological therapy. We found proteomics to be a highly effective emerging tool that has been providing important findings in the research of MS.

Introduction: Multiple Sclerosis (MS) is the most common immune-mediated chronic neurodegenerative disease of the central nervous system (CNS) affecting young people. This is due to the permanent disability, cognitive impairment, and the enormous detrimental impact MS can exert on a patient's health-related quality of life. It is of great importance to recognise it in time and commence adequate treatment at an early stage. The currently used disease-modifying therapies (DMT) aim to reduce disease activity and thus halt disability development, which in current clinical practice are monitored by clinical and imaging parameters but not by biomarkers found in blood and/or the cerebrospinal fluid (CSF). Both clinical and radiological measures routinely used to monitor disease activity lack information on the fundamental pathophysiological features and mechanisms of MS. Furthermore, they lag behind the disease process itself. By the time a clinical relapse becomes evident or a new lesion appears on the MRI scan, potentially irreversible damage has already occurred in the CNS. In recent years, several biomarkers that previously have been linked to other neurological and immunological diseases have received increased attention in MS. Additionally, other novel, potential biomarkers with prognostic and diagnostic properties have been detected in the CSF and blood of MS patients., Areas Covered: In this review, we summarise the most up-to-date knowledge and research conducted on the already known and most promising new biomarker candidates found in the CSF and blood of MS patients., Discussion: the current diagnostic criteria of MS relies on three pillars: MRI imaging, clinical events, and the presence of oligoclonal bands in the CSF (which was reinstated into the diagnostic criteria by the most recent revision). Even though the most recent McDonald criteria made the diagnosis of MS faster than the prior iteration, it is still not an infallible diagnostic toolset, especially at the very early stage of the clinically isolated syndrome. Together with the gold standard MRI and clinical measures, ancillary blood and CSF biomarkers may not just improve diagnostic accuracy and speed but very well may become agents to monitor therapeutic efficacy and make even more personalised treatment in MS a reality in the near future. The major disadvantage of these biomarkers in the past has been the need to obtain CSF to measure them. However, the recent advances in extremely sensitive immunoassays made their measurement possible from peripheral blood even when present only in minuscule concentrations. This should mark the beginning of a new biomarker research and utilisation era in MS.

A Patients: Because of the past 3 decades' extensive research, several disease modifying therapies became available, thus a paradigm change is multiple sclerosis care was necessary. In 2018 a therapeutic guideline was created recommending that treatment of persons with multiple sclerosis should take place in specified care units where the entire spectrum of disease modifying therapies is available, patient monitoring is ensured, and therapy side effects are detected and treated promptly. In 2019 multiple sclerosis care unit criteria were developed, emphasizing personnel and instrumental requirements to provide most professional care. However, no survey was conducted assessing the real-world adaptation of these criteria., Objective: To assess whether Hungarian care units fulfil international criteria., Methods: A self-report questionnaire was assembled based on international guidelines and sent to Hungarian care units focusing on 3 main aspects: personnel and instrumental background, disease-modifying therapy use, number of people living with multiple sclerosis receiving care in care units. Data on number of persons with multiple sclerosis were compared to Hungarian prevalence estimates. Descriptive statistics were used to analyse data., Results: Out of 27 respondent care units, 3 fulfilled minimum requirements and 7 fulfilled minimum and recommended requirements. The least prevalent neighbouring specialties were spasticity and pain specialist, and neuro-ophthalmologist and oto-neurologist. Only 15 centres used all available disease modifying therapies. A total number of 7213 people with multiple sclerosis received care in 27 respondent centres. Compared to prevalence estimates, 2500 persons with multiple sclerosis did not receive multiple sclerosis specific care in Hungary., Conclusion: Less than half of Hungarian care units provided sufficient care for people living with multiple sclerosis. Care units employing fewer neighbouring specialties, might have difficulties diagnosing and providing appropriate care for persons with multiple sclerosis, especially for people with progressive disease course, contributing to the reported low number of persons living with multiple sclerosis., Competing Interests: The authors have declared that no competing interests exist.

Laterality patterns of resting state networks (RSN) change in various neuropsychiatric conditions. Multiple sclerosis (MS) causes neuro-cognitive symptoms involving dysfunctional large-scale brain networks. Yet, whether healthy laterality patterns of RSNs are maintained in MS and whether altered laterality patterns explain disease symptoms has not been explicitly investigated. We analysed functional MRI and diffusion tensor imaging data from 24 relapsing-remitting MS patients and 25 healthy participants. We performed group-level independent component analysis and used dual regression to estimate individual versions of well-established RSNs. Voxelwise laterality indices were calculated for each RSN. Group differences were assessed via a general linear model-based approach. The relationship between functional laterality and white matter microstructural asymmetry was assessed using Tract-Based Spatial Statistics. Spearman's correlation was calculated between laterality indices and Brief International Cognitive Assessment for Multiple Sclerosis scores. Functional laterality of the dorsal attention network showed a significant leftward shift in the MS group in the posterior intraparietal sulcus (p < 0.033). Default-mode network laterality showed a significant leftward shift in the MS group in the angular gyrus (p < 0.005). Diminished dorsal attention network laterality was associated with increased fractional anisotropy asymmetry in the superior longitudinal fasciculus (p < 0.02). In the default-mode network, leftward laterality of the angular gyrus was associated with higher BVMT-R scores (R = - 0.52, p < 0.023). Our results confirm previous descriptions of RSN dysfunction in relapsing-remitting MS and show that altered functional connectivity lateralisation patterns of RSNs might contibute to cognitive performance and structural remodellation even in patients with mild clinical symptoms., (© 2021. The Author(s).)

Background: Multiple sclerosis may damage cognitive performance in several domains, including attention. Although attention network deficits were described during rest, studies that investigate their function during task performance are scarce., Objective: To investigate connectivity within and between task-related networks in multiple sclerosis during a visual attention task as a function of cognitive performance., Methods: A total of 23 relapsing-remitting multiple sclerosis (RRMS) patients and 29 healthy controls underwent task-functional magnetic resonance imaging (fMRI) scans using a visual attention paradigm on a 3T scanner. Scans were analysed using tensor-independent component analysis (TICA). Functional connectivity was calculated within and between components. We assessed cognitive function with the Brief International Cognitive Assessment for MS (BICAMS) battery., Results: TICA extracted components related to visual processing, attention, executive function and the default-mode network. Subject scores of visual/attention-related and executive components were greater in healthy controls ( p  < 0.032, p  < 0.023). Connectivity between visual/attention-related and default-mode components was higher in patients ( p  < 0.043), correlating with Brief Visuospatial Memory Test-Revised (BVMT-R) scores ( R  = -0.48, p  < 0.036). Patients showed reduced connectivity between the right intraparietal sulcus (rIPS) and frontal eye field (rFEF), and bilateral frontal eye fields ( p  < 0.012, p  < 0.003). Reduced rIPS-rFEF connectivity came with lower Symbol Digit Modalities Test (SDMT)/BVMT-R scores in patients ( R  = 0.53, p  < 0.02, R  = 0.46, p  < 0.049)., Conclusion: Attention-related networks show altered connectivity during task performance in RRMS patients, scaling with cognitive disability.

Objectives: Not so long ago, a novel phenotypic classification of multiple sclerosis (MS) and revisions to the McDonald diagnostic criteria were published. Good quality, standardized, and therefore comparable epidemiological data from the Central European region altogether are scarce, and data based on the aforementioned criteria are nonexistent; thus, an update is needed., Materials and Methods: Patients residing in Csongrád county with a definitive diagnosis of MS according to the 2017 McDonald criteria were included and evaluated by the 2014 revised phenotypic classification., Results: A total of 420 patients were included, of whom 313 were females (female/male ratio 2.925:1). Standardized prevalence was 101.8/100,000, and incidence was 4.44/100,000. Relapsing-remitting disease type was identified in 288 (68.57%) cases, of which 230 patients (79.86%) were treated and of which 202 patients (87.8%) showed no disease activity with their current treatment. Progressive disease type was seen in 132 (31.43%) cases, with 72 patients (54.54%) receiving treatment. More than half of the treated patients (178, 57%) were administered platform therapies, while 134 (43%) received highly active disease modifying therapies., Conclusion: The prevalence of MS in Hungary similarly to other countries shows a constant increase in the past decades. The majority of our patients received treatment and had a stable disease while being treated. The distribution of disease courses, phenotypes, and treatment status fell in line with data in the literature based on MS registries with a large number of participants. Ours is the first study to give epidemiological data based on the most recent McDonald criteria and phenotypic classification from the Central European region., (© 2020 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.)

Multiple sclerosis (MS) is the autoimmune, neurodegenerative disease of the central nervous system (CNS). Typically, it affects the young adult population, however, up to 10% of the cases, it can develop in childhood. Atypical manifestations, such as the tumefactive variant (tMS) or acute disseminated encephalomyelitis (ADEM), especially coupled with fulminant disease course, are even more rare and pose a considerable differential diagnostic and therapeutic challenge. Recently, the therapeutic strategy on the use of disease modifying therapies (DMTs) in MS has shifted to the direction of a more individualized approach, that takes the personal differences heavily into account, in particular regard to the activity and prognosis of the disease. Despite this change has only been applied to adults yet, it is plausible to predict, that it will soon be applied to pediatric patients as well, particularly, as several randomized studies are under way concerning DMTs in pediatric populations. To our best knowledge, we are the first to report a successful natalizumab treatment of pediatric fulminant tMS, in case of a 13.5 years old girl. We feel that this report demonstrates the need of early and adequate treatment in such an aggressive case, because it can reverse the course of a possibly fatal disease., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease with variable extent of remyelination coupled with the differentiation of oligodendrocytes, in which Tubulin Polymerization Promoting Protein/p25 (TPPP/p25) plays a crucial role. Previously we reported that the loss of TPPP/p25-positive oligodendrocytes in demyelinated lesions in the brain of MS patients could be a biomarker for MS [2]. In this work we tested the occurrence of TPPP/p25 in the cerebrospinal fluid (CSF) of MS patients, and by elaborating a sensitive assay for quantification of TPPP/p25 we showed that its level is significantly higher than in the case of non-MS patients. Patients with MS were diagnosed at the Department of Neurology, University of Szeged according to the clinical and laboratory diagnostic criteria of McDonald. In non-MS patients no significant pathological changes were detected on magnetic resonance imaging scans, while in MS patients multiple hyperintense T2 lesions in the white matter were detected. Kurtzke Expanded Disability Status Scale scores as well as IgG level and oligoclonal bands of MS patients were demonstrated. The sensitive assay elaborated in this study is based upon Western blot followed by chemiluminescent detection validated by human recombinant protein. The median TPPP/p25 contents in the CSF were 62.8 and 64.7 μg/L for patients with clinically isolated syndromes and relapsing remitting MS, respectively, while this value for non-MS patients was 27.9 μg/L. The enrichment of TPPP/p25 was independent of age, gender and the time period between lumbar puncture and relapse/shub. These data suggest that the TPPP/p25-based assay could be a powerful diagnostic test for MS patients., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Progressive multiple sclerosis (MS) is a chronic disease with a unique pattern, which is histologically classified into the subpial type 3 lesions in the autopsy. The lesion is also homologous to that of cuprizone (CPZ) toxin-induced animal models of demyelination. Aberration of the tryptophan (TRP)-kynurenine (KYN) metabolic system has been observed in patients with MS; nevertheless, the KYN metabolite profile of progressive MS remains inconclusive. In this study, C57Bl/6J male mice were treated with 0.2% CPZ toxin for 5 weeks and then underwent 4 weeks of recovery. We measured the levels of serotonin, TRP, and KYN metabolites in the plasma and the brain samples of mice at weeks 1, 3, and 5 of demyelination, and at weeks 7 and 9 of remyelination periods by ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) after body weight measurement and immunohistochemical analysis to confirm the development of demyelination. The UHPLC-MS/MS measurements demonstrated a significant reduction of kynurenic acid, 3-hydoxykynurenine (3-HK), and xanthurenic acid in the plasma and a significant reduction of 3-HK, and anthranilic acid in the brain samples at week 5. Here, we show the profile of KYN metabolites in the CPZ-induced mouse model of demyelination. Thus, the KYN metabolite profile potentially serves as a biomarker of progressive MS and thus opens a new path toward planning personalized treatment, which is frequently obscured with immunologic components in MS deterioration. [ABSTRACT FROM AUTHOR]

Purpose: Lesion number and burden can predict the long-term outcome of multiple sclerosis, while the localization of the lesions is also a good predictive marker of disease progression. These biomarkers are used in studies and in clinical practice, but the reproducibility of lesion count is not well-known. Methods: In total, five raters evaluated T2 hyperintense lesions in 140 patients with multiple sclerosis in six localizations: periventricular, juxtacortical, deep white matter, infratentorial, spinal cord, and optic nerve. Black holes on T1-weighted images and brain atrophy were subjectively measured on a binary scale. Reproducibility was measured using the intraclass correlation coefficient (ICC). ICCs were also calculated for the four most accurate raters to see how one outlier can influence the results. Results: Overall, moderate reproducibility (ICC 0.5–0.75) was shown, which did not improve considerably when the most divergent rater was excluded. The areas that produced the worst results were the optic nerve region (ICC: 0.118) and atrophy judgment (ICC: 0.364). Comparing high- and low-lesion burdens in each region revealed that the ICC is higher when the lesion count is in the mid-range. In the periventricular and deep white matter area, where lesions are common, higher ICC was found in patients who had a lower lesion count. On the other hand, juxtacortical lesions and black holes that are less common showed higher ICC when the subjects had more lesions. This difference was significant in the juxtacortical region when the most accurate raters compared patients with low (ICC: 0.406 CI: 0.273–0.546) and high (0.702 CI: 0.603–0.785) lesion loads. Conclusion: Lesion classification showed high variability by location and overall moderate reproducibility. The excellent range was not achieved, owing to the fact that some areas showed poor performance. Hence, putting effort toward the development of artificial intelligence for the evaluation of lesion burden should be considered. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis may damage cognitive performance in several domains, including attention. Although attention network deficits were described during rest, studies that investigate their function during task performance are scarce. Objective: To investigate connectivity within and between task-related networks in multiple sclerosis during a visual attention task as a function of cognitive performance. Methods: A total of 23 relapsing-remitting multiple sclerosis (RRMS) patients and 29 healthy controls underwent task-functional magnetic resonance imaging (fMRI) scans using a visual attention paradigm on a 3T scanner. Scans were analysed using tensor-independent component analysis (TICA). Functional connectivity was calculated within and between components. We assessed cognitive function with the Brief International Cognitive Assessment for MS (BICAMS) battery. Results: TICA extracted components related to visual processing, attention, executive function and the default-mode network. Subject scores of visual/attention-related and executive components were greater in healthy controls (p < 0.032, p < 0.023). Connectivity between visual/attention-related and default-mode components was higher in patients (p < 0.043), correlating with Brief Visuospatial Memory Test–Revised (BVMT-R) scores (R = −0.48, p < 0.036). Patients showed reduced connectivity between the right intraparietal sulcus (rIPS) and frontal eye field (rFEF), and bilateral frontal eye fields (p < 0.012, p < 0.003). Reduced rIPS-rFEF connectivity came with lower Symbol Digit Modalities Test (SDMT)/BVMT-R scores in patients (R = 0.53, p < 0.02, R = 0.46, p < 0.049). Conclusion: Attention-related networks show altered connectivity during task performance in RRMS patients, scaling with cognitive disability. [ABSTRACT FROM AUTHOR]

Background: Hypointense lesions on T1-weighted images have important clinical relevance in multiple sclerosis patients. Traditionally, spin-echo (SE) sequences are used to assess these lesions (termed black holes), but Fast Spoiled Gradient-Echo (FSPGR) sequences provide an excellent alternative. Objective: To determine whether the contrast difference between T1 hypointense lesions and the surrounding normal white matter is similar on the two sequences, whether different lesion types could be identified, and whether the clinical relevance of these lesions types are different. Methods: Seventy-nine multiple sclerosis patients' lesions were manually segmented, then registered to T1 sequences. Median intensity values of lesions were identified on all sequences, then K-means clustering was applied to assess whether distinct clusters of lesions can be defined based on intensity values on SE, FSPGR, and FLAIR sequences. The standardized intensity of the lesions in each cluster was compared to the intensity of the normal appearing white matter in order to see if lesions stand out from the white matter on a given sequence. Results: 100% of lesions on FSPGR images and 69% on SE sequence in cluster #1 exceeded a standardized lesion distance of Z = 2.3 (p < 0.05). In cluster #2, 78.7% of lesions on FSPGR and only 17.7% of lesions on SE sequence were above this cutoff value, meaning that these lesions were not easily seen on SE images. Lesion count in the second cluster (lesions less identifiable on SE) significantly correlated with the Expanded Disability Status Scale (EDSS) (R : 0.30, p ≤ 0.006) and with disease duration (R : 0.33, p ≤ 0.002). Conclusion: We showed that black holes can be separated into two distinct clusters based on their intensity values on various sequences, only one of which is related to clinical parameters. This emphasizes the joint role of FSPGR and SE sequences in the monitoring of MS patients and provides insight into the role of black holes in MS. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Evaluation of transorbital sonography measures of optic nerve diameter in the context of global and regional brain volume in multiple sclerosis." The original article contained an incomplete Acknowledgements section, which has now been corrected. The authors of the article have been supported by various grants and funding sources. The correction has been made by Szabolcs István Antal, Bálint Kincses, Dániel Veréb, András Király, Eszter Tóth, Bence Bozsik, Péter Faragó, Nikoletta Szabó, Krisztián Kocsis, Krisztina Bencsik, Péter Klivényi, and Zsigmond Tamás Kincses. [Extracted from the article]

Objective: The aim of this study was to determine the prevalence of multiple sclerosis (MS) in the population of Csongrád County, Hungary (400,128 inhabitants) and to determine the functional status (based on the Expanded Disability Status Scale; EDSS) of the patients according to the clinical forms of the disease. Methods: The diagnosis was established with the aid of the Poser diagnostic criteria, and the degree of physical disability was determined using the Kurtzke EDSS. Results: In Csongrád County, the prevalence of MS is 62/100,000. The distribution of patients according to the clinical forms of MS was as follows: 15% had the benign form, 54% had relapsing-remitting MS, 20% had secondary chronic progressive MS and 11% had the primary chronic progressive form of MS. Sixty percent of relapsing-remitting MS patients had an EDSS score of 0–4 points and 33% had an EDSS score of 4.5–6.5 points. Conclusion: The distribution of patients according to the clinical forms of the disease in this representative population is comparable to results in other regions of the world.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]