Multiple Sclerosis Study Group Research Articles

Brain neuroplasticity in multiple sclerosis patients in functional magnetic resonance imaging studies. Part 2: Effect of aerobic training

PurposeThe aim of this study was to evaluate the effects of aerobic training on motor cortical areas in multiple sclerosis (MS) patients, based on task-based functional magnetic resonance imaging (t-fMRI) as well as on brain activity at rest, according to resting state functional MRI (rs-fMRI) studies.Material and methodsMultiple sclerosis patients were divided into 2 groups consisting of 14 participants each: the MS study group and the MS control group. All MS patients underwent clinical assessment and MRI examination, twice: in the MS study group at the time of inclusion in the study and after a 4-week period of aerobic training, whereas in the MS control group it happened at the time of inclusion and after a period of one month without exercise rehabilitation. The MRI study protocol included rs-fMRI and t-fMRI sequences, which were the grounds for an analysis of resting state networks (RSN) as well as peak level and cluster level parameters within motor cortex areas – the primary motor cortex, premotor area, and supplementary motor area, respectively.ResultsIn the MS study group, aerobic training improved the clinical condition and decreased the functional correlation between the sensorimotor network and the salience network. Also, significant decreases of the mean cluster level (72.42 vs. 38.35) and peak level values (10.89 vs. 7.64) were observed in the contralateral primary motor cortex in this group of patients between examinations.ConclusionsAerobic training not only improves physical performance but also contributes to changes in brain activity – both within RSN and motor cortex areas in MS patients.

Clinico-radiologic Spectrum and Outcome of Pediatric Acquired Demyelinating Disorders of Central Nervous System: A Retrospective Indian Tertiary Care Hospital Cohort.

Pediatric acquired demyelinating syndrome (ADS) constitutes a group of treatable disorders with acute neurologic dysfunction. Neuroimaging has played a significant role in diagnosis of ADS. We describe clinico-radiologic spectrum, outcomes, and comparison of the groups: acute disseminated encephalomyelitis (ADEM), neuromyelitis optica spectrum disorder (NMOSD), clinically isolated syndrome (CIS), multiple sclerosis (MS), and myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). Retrospective review of 70 children with ADS at a tertiary care hospital over 15 years (2008-2023) was performed. Diagnosis was assigned as per International Pediatric Multiple Sclerosis Study Group criteria 2016. Fisher's exact and chi-square tests were applied. Thirty-nine boys and 31 girls aged 8.2 ± 4.0 years with CIS (n = 27), ADEM (n = 16), NMOSD (n = 13), MS (n = 1), and MOGAD (n = 13) were included. Clinical syndromes with positive significant association included polyfocal symptoms, encephalopathy in ADEM, optic neuritis (ON) in MOGAD, brainstem, area postrema syndrome in NMOSD. MOGAD presented with atypical presentations like prolonged fever (PF; 76.9%) and aseptic meningitis (23%). Seropositivity for myelin oligodendrocyte glycoprotein immunoglobulin-G was 62% and for NMO-IgG 2.6%. Neuroimaging of MOGAD showed lesions predominantly in basal ganglia/thalami (69.2%), optic nerve (46.2%), and cerebellum (46.2%). Imaging patterns between ADEM and MOGAD were comparable except for more ON (p = 0.004), spinal cord (p = 0.01), and cerebellar lesions (p = 0.03) in MOGAD. Area postrema lesion was unique to NMOSD. All patients received immunotherapy, of whom 91.4% (n = 64) had good recovery, 8.6% (n = 6) had functional limitation on modified Rankin scale at discharge, and 12 (17.1%) relapsed. The largest group was CIS. Seropositivity of MOG was high with atypical presentations like PF and aseptic meningitis. Specific neuroimaging patterns correlated with ADS categories. Short-term outcome with immunotherapy was favorable in spite of relapses.

Juvenile multiple sclerosis: addressing epidemiology, diagnosis, therapeutic, and prognostic updates along with cognitive dysfunction and quality of life.

Juvenile multiple sclerosis (JMS) is a rare but significant subtype of multiple sclerosis (MS) that affects a small percentage of patients under the age of 10 and 3-5% of all MS patients. Despite its rarity, JMS poses unique challenges in terms of diagnosis, treatment, and management, as it can significantly impact a child or adolescent's physical, cognitive, and emotional development. JMS presents with a varying spectrum of signs and symptoms such as coordination difficulties and permanent cognitive dysfunctions and may include atypical clinical features such as seizures, acute disseminated encephalomyelitis, and optic neuritis, making diagnostic evaluations challenging. Whilst the biology of JMS shares similarities with adult-onset MS, there exist notable distinctions in disease progression, clinical manifestations, and ultimate prognoses. The International Pediatric MS Study Group (IPMSSG) was founded in 2005 to improve understanding of JMS, but there remains a lack of knowledge and guidelines on the management of this condition. This review summarizes the current knowledge on JMS, including its epidemiology, clinical presentations, diagnostic challenges, current treatment options, and outcomes. Current treatment options for JMS include disease-modifying therapies, but JMS can also result in impaired quality of life and psychiatric comorbidity, highlighting the need for comprehensive care for affected children. Through gathering and analyzing scattered studies and recent updates on JMS, the authors aim to address the gaps in current knowledge on JMS and provide an improved understanding of appropriate care for affected children. By doing so, this review hopes to contribute to improving the quality of life and outcomes for JMS patients.

Features of multiple sclerosis in childhood in the Republic of Tatarstan

Multiple sclerosis (MS) in children and adolescents is a genuine concern of pediatric neurology that specialists in all countries are dealing with. To date, neither the causes of onset nor the individual components of the pathogenesis of the disease have been reliably clarified, and the modern, changing picture of the clinical manifestation of the disease sometimes complicates timely diagnosis even in adult patients. There are more such questions in pediatric MS.Objective: to study the prevalence and clinical features of MS in children in the Republic of Tatarstan.Material and methods. We conducted a survey and data analysis of 128 children and adolescents aged 0 to 18 years inclusive. The examination of patients included neurological examination according to the classical scheme, neuroimaging examination, neurophysiological examination and cerebrospinal fluid examination. The diagnosis was based on the current (as of the time of diagnosis) criteria of McDonald and the International Pediatrics MS Study Group criteria. The severity of the patients' clinical condition was assessed using the Expanded Disability Status Scale (EDSS).Results. MS was diagnosed in 99 cases (77.3%), clinically isolated syndrome – in 10 (7.8%), acute disseminated encephalomyelitis – in 5 (3.9%), bilateral optic neuritis – in two patients (1.6%), disseminated encephalomyelitis – in one case (0.8%); other central nervous system diseases were diagnosed in 11 (8.6%) patients. After a detailed examination, the group “other diseases of the central nervous system” included such conditions as cerebral angiopathy, neurofibromatosis, brain mass, structural focal epilepsy, sequelae of viral encephalitis, and hereditary leukodystrophy. Among the patients, girls aged 15–17 years predominated. Monofocal manifestations were more frequently observed at debut. Moreover, the absolute predominance of the remitting type of course was also noted.Conclusion. The data obtained suggest a predominance of the predominantly remitting course type of MS with a monofocal onset, which is consistent with data from other studies of MS in pediatric practice.

Uveitis prior to clinical presentation of Multiple Sclerosis (MS) is associated with better MS prognosis.

ObjectiveAn association between uveitis and multiple sclerosis (MS) is well-established, but the actual nature of that association remains poorly understood. We sought to determine the association between the presence of a uveitis diagnosis prior to an MS diagnosis compared to no pre-existing uveitis diagnosis in MS patients.MethodsPatients in whom the presentation of uveitis preceded the presentation of MS (study group) and patients with MS and no uveitis (control group) were randomly selected at a ratio of 1:3 from the Sheba Multiple Sclerosis Center computerized database.ResultsEleven patients presented with uveitis prior to MS diagnosis (study group), and 31 randomly selected patients had MS without uveitis (control group). Only one patient in the study group deteriorated to EDSS 3 during the follow-up period, compared to 15 patients in the control group (9.1% vs 48.4%, P = 0.049). None of the patients in the study group reached EDSS 6 during the 10 years of follow-up compared to 6 (19.4%) patients in the control group (P = 0.194).ConclusionsMS patients who presented with uveitis that preceded their neurological symptoms of MS demonstrated a clinically significant better neurological prognosis, than our MS patients with no uveitis.

Differential diagnosis of multiple sclerosis in children

At the onset, multiple sclerosis (MS) in children is characterized by a phase of active inflammation with extensive demyelination of the white matter of the CNS, which often mimics this nosology with a whole spectrum of inflammatory demyelinating diseases such as ADEM, anti-MOG encephalitis, ONMSD. In order to formalize the diagnostic process, the International Pediatric Multiple Sclerosis Study Group (IPMSSG) proposed diagnostic criteria for the main immune-mediated demyelinating diseases of the CNS in children, which, in theory, should simplify the diagnostic search. However, in practice, the range of nosologies in the course of differential diagnosis is much wider and often it is not possible to establish an unambiguous diagnosis in the early stages. The authors analyze their own clinical observations based on a sample of 100 pediatric patients with a referral diagnosis of «MS?» and describe a clinical case of the onset of highly active MS with an assessment of the dynamics of the clinical and paraclinical course of the disease.

Paediatric multiple sclerosis: a lesson from TERIKIDS

Biological plausibility and convincing evidence from subgroup analyses indicate that the treatments proven efficacious for adults with multiple sclerosis are generally as effective, or more, in patients who are younger and have more active disease; 1 Signori A Schiavetti I Gallo F Sormani MP Subgroups of multiple sclerosis patients with larger treatment benefits: a meta-analysis of randomized trials. Eur J Neurol. 2015; 22: 960-966 Google Scholar such findings give a rationale for use of these drugs in paediatric multiple sclerosis. To put it another way, there is no apparent reason why effective treatments for adults who have relapsing-remitting multiple sclerosis should be not effective in children. Arguably the most important requirement to advance the care of paediatric patients with multiple sclerosis is the assessment of long-term safety, to ensure that treatment during childhood and adolescence does not expose patients to future risk. The ways in which the safety and efficacy of drugs might be investigated in patients with paediatric multiple sclerosis have been discussed extensively in a consensus paper from the International Paediatric Multiple Sclerosis Study Group (IPMSSG). 2 Waubant E Banwell B Wassmer E et al. Clinical trials of disease-modifying agents in pediatric MS: opportunities, challenges, and recommendations from the IPMSSG. Neurology. 2019; 92: e2538-e2549 Google Scholar Safety and efficacy of teriflunomide in paediatric multiple sclerosis (TERIKIDS): a multicentre, double-blind, phase 3, randomised, placebo-controlled trialNo significant difference in time to first confirmed clinical relapse was found, possibly because more patients than expected switched from the double-blind to the open-label treatment period because of high MRI activity. Key secondary imaging analyses and a prespecified sensitivity analysis of probability of relapse or high MRI activity suggest that teriflunomide might have beneficial effects in children with relapsing multiple sclerosis by reducing the risk of focal inflammatory activity. Full-Text PDF

Acute disseminated encephalomyelitis: A retrospective study of 20 children in a pediatrics department in Tunisia

BackgroundAcute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disorder of the central nervous system. Little information is available about the clinical and neuroradiological profile or the follow-up of this disease in Tunisian children. AimTo determine the clinical, laboratory, and radiological features and the outcome of ADEM in children admitted to the pediatrics department of a university hospital in Tunisia. MethodsAll children ≤ 18 years old presenting with ADEM and admitted to the tertiary referral center for pediatrics at Sahloul University Hospital from January 2000 to December 2020 were included in the study. The diagnosis of ADEM was confirmed according to the international pediatric multiple sclerosis study group criteria. ResultsA total of 20 patients (13 girls and 7 boys) fulfilled the diagnostic criteria for ADEM. The mean age at diagnosis was 5.6 years. The clinical presentation included polyfocal neurological signs such as cranial hypertension (45%), seizures (35%), and motor weaknesses (55%). Pyramidal tract signs and cranial nerve palsies were noted in 55% of cases. Brain magnetic resonance imaging showed particular features, namely, a relapsing tumor-like form in one case, and optic neuritis and demyelinating lesions of the white matter in the brain and the spinal cord with gadolinium cerebral ring-like enhancement in another case. The treatment consisted of intravenous immunoglobulin in 16 cases (80%) and corticosteroid in 19 cases (95%). Plasmapheresis was used for one patient. Complete recovery was observed in 12 patients (60%); 19 patients (95%) had a monophasic course of the disease while only one patient developed multiphasic ADEM. ConclusionsADEM remains a difficult diagnosis in children. Nevertheless, after prompt diagnosis and adequate treatment, most children with ADEM have a favorable outcome with restitutio ad integrum.

Fingolimod as a first- or second-line treatment in a mini-series of young Hellenic patients with adolescent-onset multiple sclerosis: focus on immunological data.

Pediatric onset multiple sclerosis(POMS) is characterized by a highly active profile, often warranting treatment with high efficacy disease-modulating therapies (DMTs). Fingolimod, an oral sphingosine-1-phosphate receptor modulator, is the first Food and Drug Administration (FDA)- and European Medicines Agency (EMA)-approved DMT for the treatment of POMS. Our aim is to present real-world data of seven fingolimod-treated POMS-patients, recruited in a single MS center in Greece. Clinical and imaging/laboratory data from 7 Hellenic patients fulfilling the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria for POMS diagnosis, who have received fingolimod treatment, were selected. Human leukocyte antigen (HLA) genotyping was performed with standard low-resolution sequence-specific oligonucleotide techniques. Three patients were treatment-naïve adolescents who received fingolimod as first-line treatment. Two experienced ongoing clinical and radiological disease activity and have been switched to natalizumab. The remaining cases were post-adolescent adults with POMS, where the vast majority experienced total/near-total disease remission. Fingolimod was generally well-tolerated. Two patients with high disease activity carried the HLA-DRB1*03 allele, while five patients were carriers of at least one of the HLA-DRB1*04, HLA-DRB1*13, and HLA-DRB1*14 alleles, which when not combined with HLA-DRB1*03 showed a trend towards a more favorable clinical course. Fingolimod responders showed a trend towards increased CD(16-56)+NK cell counts in immunophenotyping assays. Our preliminary results support that response of POMS patients to fingolimod may be partially dependent on age and previous DMT, with younger and treatment-naïve patients presenting worse outcomes. The role of immunogenetics and immunophenotyping in personalized treatment warrants investigation in larger and more diverse populations.

Current international trends in the treatment of multiple sclerosis in children—Impact of the COVID-19 pandemic

BackgroundOnly recently has the first disease-modifying therapy been approved for children with multiple sclerosis (MS) and practice patterns including substantial off-label use have evolved. Understanding attitudes towards treatment of paediatric MS and whether this has changed due to the ongoing COVID-19 pandemic is vital to guide future therapeutic trials and for developing guidelines that reflect practice. MethodsWe performed an online survey within the International Paediatric Multiple Sclerosis Study Group between July and September 2020. The survey was sent to 130 members from 25 countries and consisted of five sections: demographic data, treatment, disease modifying therapies and COVID-19, outcome and three patient cases. ResultsThe survey was completed by 66 members (51%), both paediatric neurologists and adult neurologists. Fingolimod and β-interferons were the most frequently used disease-modifying therapies, especially among paediatric neurologists. Almost a third (31%) of respondents had altered their prescribing practice due to COVID-19, in particular at the beginning of the pandemic. ConclusionsThe survey results indicate a tendency of moving from the traditional escalation therapy starting with injectables towards an early start with newer, highly effective disease modifying therapies. The COVID-19 pandemic only slightly affected prescribing patterns and treatment choices in paediatric MS.

Evaluation of inflammatory acquired demyelinating syndromes in children: a single-center experience.

To evaluate the clinical and neuroimaging features of pediatric acquired demyelinating syndromes (ADS) in a tertiary pediatric neurology clinic in Turkey. All children diagnosed with any subset of ADS between 2013 and 2018 were included in this retrospective cohort study. Forty-two patients (21 female) with a median follow-up period of 30months were included. The median age of the patients at disease onset was 11years (range 1.5-17years). The most common pediatric ADS categories according to the International pediatric Multiple Sclerosis Study Group consensus classification criteria were acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS), each of which seen in 15 patients, followed by clinically isolated syndrome (CIS) (n = 11) and Neuromyelitis Optica Spectrum Disorder (NMOSD) (n = 1). At the first clinical event, children with ADEM significantly differed from the children affected by MS and CIS in terms of the following parameters: median age at onset (7 vs. 13.5 and 14.5years; p < 0.001), encephalopathy (93.3 vs 0% and 0%; p < 0.001), and basal ganglia/thalamus lesions (73.3 vs 9.1% and 9.1%; p < 0.001). The frequency of seizure and pleocytosis were higher in ADEM group than MS group (p < 0.05), whereas oligoclonal bands (p < 0.001) and periventricular white matter lesions (p < 0.01) were more frequently observed in MS patients. Rituximab was used with great success in the prevention of relapses in 3 patients: NMOSD (n = 1), MS (n = 1) and ADEM followed by recurrent optic neuritis (n = 1). Our results define the longitudinal disease course of various ADS categories in a single referral center. In addition, this study compares various clinical, laboratory and neuroimaging features between these ADS categories.

Multiple Sclerosis Patient Management During the COVID-19 Pandemic: Practical Recommendations From the Portuguese Multiple Sclerosis Study Group (GEEM).

The spread of the COVID-19 pandemic has imposed significant challenges on healthcare provision, requiring changes in the conventional patient management, particularly in chronic diseases like multiple sclerosis (MS). To increase patient safety and reduce the risk of infection, while ensuring an appropriate and regular follow-up, tele-medicine gained prominence as a valid alternative to face-to-face appointments. However, the urgency of the implementation and the lack of experience in most MS centers led to “ad hoc” and extremely diverse approaches, which now merit to be standardized and refined. Indeed, while tele-consultation cannot fully replace face-to-face visits, it certainly can, and will, be incorporated as part of the routine care of MS patients in the near future. Bearing this in mind, the Portuguese Multiple Sclerosis Study Group (GEEM) has developed a set of recommendations for the usage of tele-medicine in the management of MS patients, both during the pandemic and in the future. The consensus was obtained through a two-step modified Delphi methodology, resulting in 15 recommendations, which are detailed in the manuscript.

Clinical comparative analysis of monophasic and multiphasic acute disseminated encephalomyelitis in adults.

This study aims to explore the clinical features and prognostic factors for relapse of acute disseminated encephalomyelitis (ADEM) in adults. 56 patients with ADEM were retrospectively analyzed. The epidemiological characteristics, clinical manifestations, laboratory features, magnetic resonance imaging (MRI), treatment and prognosis data of these patients were analyzed using the χ2 test for categorical variables and Mann-Whitney U-test for continuous variables. Then, the clinical characteristics and recurrence factors were summarized. 56 patients with ADEM, based on the criteria of the International Pediatric Multiple Sclerosis Study Group, were recruited to the study. Among these patients, 31 were male and 25 were female. Furthermore, 13 patients had multiphasic ADEM, and 29 patients (52%) had definite incentive factors before onset. The commonest presenting symptoms and signs were fever (36%), disturbance of consciousness (52%), mental disorder (38%), seizure (14%), headache and dizziness (43%), optic neuritis (34%), autonomic nervous system symptoms (43%), limb paralysis or abnormal sensation (73%), and unilateral or bilateral pyramidal tract signs (48%). Inflammatory changes in the cerebrospinal fluid were prominent. MRI T2-weighted and fluid-attenuated inversion recovery images displayed multiple or large flaky high signals, and the lesions were usually different in the number and distribution of these lesions. Intravenous corticosteroids and/or immunoglobulin were still important treatments in the acute phase. After treatment, 38 patients completely recovered, 9 patients had neurologic deficits, and 9 patients died. ADEM in adults is not uncommon, its clinical features are complex and varied, and some of these are multiphasic. There may be some potential clinical predictors at first onset.

Polymorphic variants in the PVT1 locus affect multiple sclerosis severity

Multiple sclerosis (MS) is a chronic autoimmune disease, in the pathogenesis of which the concurrence of demyelination of central nervous system (CNS) axons and neurodegeneration plays a role and which is accompanied by progressive neurological dysfunction. Long-term monitoring of patients with MS is needed to rate its severity according to existing scales; it is therefore very relevant to search for genomic markers that can predict the rate of disease progression at early stages. The impact of polymorphic variants in the PVT1 locus on MS severity has not been previously studied.Objective: to analyze the association of the polymorphic variants rs4645948 in the MYC gene and rs2114358 and rs4410871) in the PVT1 genes with MS severity according to the Multiple Sclerosis Severity Scale (MSSS) separately and as part of biallelic combinations, as well as the possible linkage disequilibrium of the studied single nucleotide polymorphisms for establishing the independence of the observed associations.Patients and methods. The investigation enrolled 468 Russian MS patients who did not take immunomodulating drugs before blood testing. The patients were divided into two groups: 1) relatively mild MS (MSSS ≤3.5) and 2) relatively severe MS (MSSS &gt;3.5). The polymorphic variants in the PVT1 locus were genotyped by a real-time polymerase chain reaction assay.Results and discussion. In the MS study group, the carriage of the allele of PVT1 (rs2114358)*G turned out to be associated with the severe course of the disease (pf=0.042; odds ratio (OR)=1.41). The significance of the association increases in the simultaneous carriage of this allele with another variant of the same gene – PVT1 (rs4410871)*T (pf=0.024; OR=1.58). There was no linkage disequilibrium between the components of the biallelic combination.Conclusion. The polymorphic variants in the PVT1 locus are associated with the severity of MS.

Harmonization of real-world studies in multiple sclerosis: Retrospective analysis from the rirems group

Worldwide multiple sclerosis (MS) centers have coordinated their efforts to use data acquired in clinical practice for real-world observational studies. In this retrospective study, we aim to harmonize outcome measures, and to evaluate their heterogeneity within the Rising Italian Researchers in MS (RIReMS) study group. RIReMS members filled in a structured questionnaire evaluating the use of different outcome measures in clinical practice. Thereafter, thirty-four already-published papers from RIReMS centers were used for heterogeneity analyses, using the DerSimonian and Laird random-effects method to compute the between-study variance (τ2). Based on questionnaire results, we defined basic modules for diagnosis and follow-up, consisting of outcome measures recorded by all participating centers at the time of diagnosis, and, then, at least annually; we also defined more detailed/optional modules, with outcome measures recorded less frequently and/or in the presence of specific clinical indications. Looking at heterogeneity, we found 5-year variance in age at onset (ES=27.34; 95%CI=26.18, 28.49; p<0.01; τ2=4.76), and 7% in female percent (ES=66.42; 95%CI=63.08, 69.76; p<0.01; τ2=7.15). EDSS variance was 0.2 in studies including patients with average age <36.1 years (ES=1.96; 95%CI=1.69, 2.24; p<0.01; τ2=0.19), or from 36.8 to 41.1 years (ES=2.70; 95%CI=2.39, 3.01; p<0.01; τ2=0.18), but increased to 3 in studies including patients aged >41.4 years (ES=4.37; 95%CI=3.40, 5.35; p<0.01; τ2=2.96). The lowest variance of relapse rate was found in studies with follow-up duration ≤2 years (ES=9.07; 95%CI=5.21, 12.93; p=0.02; τ2=5.53), whilst the lowest variance in EDSS progression was found in studies with follow-up duration >2 years (ES=5.41; 95%CI=3.22, 7.60; p=0.02; τ2=1.00). We suggest common sets of biomarkers to be acquired in clinical practice, that can be used for research purposes. Also, we provide researchers with specific indications for improving inclusion criteria and data analysis, ultimately allowing data harmonization and high-quality collaborative studies.

Pediatric multiple sclerosis: from clinical basis to imaging spectrum and differential diagnosis.

Pediatric multiple sclerosis (MS) deserves special attention because of its impact on cognitive function and development. Although knowledge regarding pediatric MS has rapidly increased, understanding the peculiarities of this population remains crucial for disease management. There is limited expertise about the efficacy and safety of current disease-modifying agents. Although pathophysiology is not entirely understood, some risk factors and immunological features have been described and are discussed herein. While the revised International Pediatric MS Study Group diagnostic criteria have improved the accuracy of diagnosis, the recently revised McDonald criteria also offer some new insights into the pediatric population. It is fundamental that radiologists have strong knowledge about the vast spectrum of demyelinating disorders that can occur in childhood to ensure appropriate diagnosis and provide early treatment.

HLA-DRB1 allele impact on pediatric multiple sclerosis in a Hellenic cohort.

BackgroundPediatric-onset multiple sclerosis (POMS) is considered a complex disease entity with many genetic and environmental factors implicated in its pathogenesis. Linkage studies in Caucasian adult populations consistently demonstrate the major histocompatibility complex and its HLA (human leukocyte antigen) polymorphisms as the genetic locus most strongly linked to MS.ObjectiveTo investigate the frequencies and possible clinical and imaging correlations of HLA-DRB1 alleles in a Hellenic POMS sample.MethodsFifty POMS patients fulfilling the IPMSSG (International Pediatric Multiple Sclerosis Study Group) criteria were enrolled using 144 adult-onset MS (AOMS) patients and 246 healthy controls for comparisons. HLA genotyping was performed with standard low-resolution sequence-specific oligonucleotide (SSO) techniques. Clinical and imaging correlations with specific HLA-DRB1 alleles were also examined.ResultsThe HLA-DRB1*03 genotype was significantly higher in POMS patients compared to both the AOMS population (26% vs. 12.5%, p = 0.042) and the general population (26% vs. 12.6%, p = 0.004). HLA-DRB1*03-positive POMS patients had significantly more relapses (6.9 ± 4.9 vs. 4.2 ± 4.4, p = 0.005) and more thoracic spinal cord lesions than HLA-DRB1*03-negative patients (61.5% vs. 27%, p = 0.043).ConclusionIn our Hellenic population, HLA-DRB1*03 allele confers increased risk for POMS and it is also correlated with possibly increased disease activity, expanding the existing knowledge on HLA associations and POMS.

Predictors of Evolution Into Multiple Sclerosis After a First Acute Demyelinating Syndrome in Children and Adolescents.

Background/Objective: The aim of the study was to estimate the rate of evolution or for multiple sclerosis (MS), after a first acute demyelinating event (ADE) in pediatric patients, and to investigate the variables that predict this evolution.Methods: We retrospectively evaluated the clinical and neuroradiological features of children who presented a first ADE between January 2005 and April 2017. All patients included underwent a baseline MRI, a cerebrospinal fluid and blood analysis, including virological examinations. The evolution into MS was determined by the 2013 International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria. Clinical and radiological features predictive of MS were determined using multivariate analyses.Results: Ninety-one patients were selected (mean age at onset: 10.11 ± 4.6). After a mean follow-up of 5.6 ± 2.3 years, 35% of patients' conditions evolved to MS. In the logistic multivariate analysis of clinical and laboratory data, the best predictors of evolution into MS were: the presence of oligoclonal bands in CSF (p < 0.001), past infection with EBV (p < 0.001), periventricular lesions (p < 0.001), hypointense lesions on T1 (p < 0.001), and lesions of the corpus callosum (p < 0.001) including Dawson fingers (p < 0.001).Conclusion: Our findings suggest that a pattern of neuroimaging and laboratory findings may help to distinguish between, at clinical onset, children with a monophasic syndrome (clinically isolated syndrome or acute disseminated encephalomyelitis) from those who will develop MS.

Recommendations About Multiple Sclerosis Management During Pregnancy, Partum and Post-Partum: Consensus Position of The Portuguese Multiple Sclerosis Study Group and The Portuguese Society of Obstetrics and Maternal-Fetal Medicine

Multiple sclerosis typically affects young women of reproductive age. Therefore, all healthcare providers involved in the follow-up of multiple sclerosis patients must be prepared to discuss pregnancy and breastfeeding issues, and provide the best possible counselling. However, there are still many doubts and heterogeneous clinical approaches partly due to the lack of consensus and guidelines. Concerning the handling of disease modifying therapies during pregnancy and the postpartum period, uncertainties have been complicated by the increase in recent years of the number of available treatments. This article aims to present the state-of-the-art and provide guidance based on the best level of available evidence and expert opinion regarding the management of multiple sclerosis patients at different stages: pregnancy planning, pregnancy, partum, and the postpartum period.

Unraveling treatment response in multiple sclerosis: A clinical and MRI challenge.

Over the last few decades, the improved diagnostic criteria, the wide use of MRI, and the growing availability of effective pharmacologic treatments have led to substantial advances in the management of multiple sclerosis (MS). The importance of early diagnosis and treatment is now well-established, but there is still no consensus on how to define and monitor response to MS treatments. In particular, the clinical relevance of the detection of minimal MRI activity is controversial and recommendations on how to define and monitor treatment response are warranted. An expert panel of the Magnetic Resonance Imaging in MS Study Group analyzed and discussed published studies on treatment response in MS. The evolving concept of no evidence of disease activity and its effect on predicting long-term prognosis was examined, including the option of defining a more realistic target for daily clinical practice: minimal evidence of disease activity. Advantages and disadvantages associated with the use of MRI activity alone and quantitative scoring systems combining on-treatment clinical relapses and MRI active lesions to detect treatment response in the real-world setting were also discussed. While most published studies on this topic involved patients treated with interferon-β, special attention was given to more recent studies providing evidence based on treatment with other and more efficacious oral and injectable drugs. Finally, the panel identified future directions to pursue in this research field.