Pediatric Multiple Sclerosis Study Group Research Articles

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.

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.

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.

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.

Implications of the International Paediatric Multiple Sclerosis Study Group consensus criteria for paediatric acute disseminated encephalomyelitis: a nationwide validation study.

The International Paediatric Multiple Sclerosis Study Group (IPMSSG) has proposed criteria for acute disseminated encephalomyelitis (ADEM) not evaluated in clinical practice. Our objective was to assess epidemiological implications of the IPMSSG criteria for ADEM in a cohort study using prospectively collected data. We identified all diagnosed cases of ADEM in Denmark between 2008 and 2015 from the Danish National Patient Register by International Classification of Diseases 10 codes assigned to acute demyelinating episodes, and we reviewed all medical records to validate ADEM. We found 52 children up to the age of 18 years with a verified clinical diagnosis of ADEM (incidence rate 0.54/100000 person-years; all had abnormal brain magnetic resonance imaging). Only 18 (35%) fulfilled the IPMSSG criteria regarding encephalopathy and polyfocal neurological deficits. Among all 52 children with ADEM, 33 per cent had clinical sequelae after a median follow-up of 4 years 6 months (range: 10mo-8y 3mo). Surprisingly, none progressed to multiphasic ADEM or multiple sclerosis, but median age at end of follow-up was only 10 years 9 months (range: 2y-24y 3mo). Among 52 children with ADEM, none converted to multiphasic ADEM or multiple sclerosis (median follow-up: 4y 6mo; range: 10mo-8y 3mo). Applying the IPMSSG criteria to all children with a diagnosis of ADEM leaves 65 per cent of the cases without a diagnosis and lowers the incidence rate of paediatric ADEM. The incidence of paediatric acute disseminated encephalomyelitis (ADEM) was 0.54 per 100000 person-years in children younger than 18 years. Only 35 per cent of children with ADEM fulfilled the International Paediatric Study Group consensus criteria. ADEM in clinical practice was primarily based on magnetic resonance imaging findings. Paediatric neurologists diagnosed ADEM in the absence of encephalopathy. None of the children with ADEM progressed to multiple sclerosis/multiphasic ADEM during follow-up.

Implications of the International Paediatric Multiple Sclerosis Study Group Consensus Criteria for Paediatric Acute Disseminated Encephalomyelitis: a Nationwide Validation Study (S35.005)

Implications of the International Paediatric Multiple Sclerosis Study Group Consensus Criteria for Paediatric Acute Disseminated Encephalomyelitis: a Nationwide Validation Study (S35.005)

Pediatric multiple sclerosis: epidemiology, clinical aspects, diagnosis and treatment.

Neurodegenerative Disease ManagementVol. 7, No. 6s SupplementPediatric multiple sclerosis: epidemiology, clinical aspects, diagnosis and treatmentAngelo GhezziAngelo Ghezzi*Author for correspondence: E-mail Address: angelo.ghezzi@asst-valleolona.it Centro Studi Sclerosi Multipla, Ospedale di Gallarate, Via Pastori 4, 21013, Gallarate, ItalySearch for more papers by this authorPublished Online:16 Nov 2017https://doi.org/10.2217/nmt-2017-0037AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: diagnosisMRIpediatric multiple sclerosisReferences1 Ghezzi A, Baroncini D, Zaffaroni M, Comi G. Pediatric versus adult MS: similar or different? Mult. Scler. Demyelinating Disord. 2, 5 (2017).Crossref, Google Scholar2 Ghezzi A. Clinical characteristics of multiple sclerosis with early onset. Neurol. Sci. 25(Suppl. 4), S336–S339 (2004).Crossref, Medline, Google Scholar3 Renoux C, Vukusic S, Mikaeloff Y et al. Natural history of multiple sclerosis with childhood onset. N. Engl. J. Med. 356(25), 2603–2613 (2007).Crossref, Medline, CAS, Google Scholar4 Polman CH, Reingold SC, Banwell B et al. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann. Neurol. 69(2), 292–302 (2011).Crossref, Medline, Google Scholar5 Krupp LB, Tardieu M, Amato MP et al. International Pediatric Multiple Sclerosis Study Group criteria for pediatric multiple sclerosis and immune-mediated central nervous system demyelinating disorders: revisions to the 2007 definitions. Mult. Scler. 19(10), 1261–1267 (2013).Crossref, Medline, Google Scholar6 Verhey LH, Branson HM, Shroff MM et al. MRI parameters for prediction of multiple sclerosis diagnosis in children with acute CNS demyelination: a prospective national cohort study. Lancet Neurol. 10(12), 1065–1073 (2011).Crossref, Medline, Google Scholar7 Neuteboom RF, Boon M, Catsman Berrevoets CE et al. Prognostic factors after a first attack of inflammatory CNS demyelination in children. Neurology 71(13), 967–973 (2008).Crossref, Medline, CAS, Google Scholar8 Heussinger N, Kontopantelis E, Gburek-Augustat J et al. Oligoclonal bands predict multiple sclerosis in children with optic neuritis. Ann. Neurol. 77(6), 1076–1082 (2015).Crossref, Medline, Google Scholar9 Hacohen Y, Absoud M, Deiva K et al. Myelin oligodendrocyte glycoprotein antibodies are associated with a non-MS course in children. Neurol. Neuroimmunol. Neuroinflamm. 2(2), e81 (2015).Crossref, Medline, Google Scholar10 Sadaka Y, Verhey LH, Shroff MM et al. 2010 McDonald criteria for diagnosing pediatric multiple sclerosis. Ann. Neurol. 72(2), 211–223 (2012).Crossref, Medline, Google Scholar11 Ghezzi A. Randomized clinical trials (RCTs) in pediatric multiple sclerosis: are they really necessary? Mult. Scler. 23(7), 1042–1043 (2017).Crossref, Medline, Google Scholar12 Ghezzi A, Banwell B, Boyko A et al. The management of multiple sclerosis in children: a European view. Mult. Scler. 16(10), 1258–1267 (2010).Crossref, Medline, Google Scholar13 Chitnis T, Tenembaum S, Banwell B et al. Consensus statement: evaluation of new and existing therapeutics for pediatric multiple sclerosis. Mult. Scler. 18(1), 116–127 (2012).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetailsCited ByObesity in Pediatric-Onset Multiple Sclerosis20 July 2021 | Neurology - Neuroimmunology Neuroinflammation, Vol. 8, No. 5Needs and Experiences of Children and Adolescents with Pediatric Multiple Sclerosis and Their Caregivers: A Systematic Review25 May 2021 | Children, Vol. 8, No. 6 Vol. 7, No. 6s Follow us on social media for the latest updates Metrics Downloaded 201 times History Received 8 September 2017 Accepted 19 September 2017 Published online 16 November 2017 Published in print November 2017 Information© 2017 Future Medicine LtdKeywordsdiagnosisMRIpediatric multiple sclerosisFinancial & competing interests disclosureA Ghezzi has received honoraria from Almirall, Biogen, Genzyme, Merck-Serono, Novartis and Teva; and speakers’ bureau from Biogen, Genzyme, Merck-Serono, Novartis and Teva. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.Writing assistance was provided by Content Ed Net (Madrid, Spain), with funding from Almirall SA (Barcelona, Spain).PDF download

The natural course of pediatric clinically isolated syndrome

Objective: Clinically isolated syndrome (CIS) is the first clinical central nervous system demyelinating event, compatible with the possible future development of multiple sclerosis (MS). Diagnostic criteria for pediatric CIS were first proposed by the International Pediatric Multiple Sclerosis Study Group (IPMSSG) in 2007 and then revised in 2012. CIS is characterized by monofocal or polyfocal events without encephalopathy, unless explained by fever. The most common clinical presentations of CIS in children are optic neuritis (ON), a brainstem and/or cerebellar syndrome, a spinal cord syndrome or syndrome attributed to cerebral hemispheres. The aim of this study was to identify the natural course of pediatric patients with CIS in Slovenia and to assess potential patient characteristics that predict progression to MS. Methods: We retrospectively reviewed the medical records of all pediatric patients (<18 years old) treated at the University Children’s Hospital Ljubljana who presented with CIS between 2006 and 2016. Results: We identified 39 patients with CIS in the 11 year period. The median age at the onset of symptoms was 15,4 years. The most common clinical presentation of CIS were symptoms attributed to cerebral hemispheric dysfunction and ON. Twenty (51%) patients experienced a second demyelinating episode. The mean interval between the first event and the recurrent episode was 11 ± 14 months. The mean follow-up was 3,2 ± 2 years. Twenty-nine (74%) patients developed childhood onset MS. Female sex was significantly associated with the development of MS (p=0,038). There was a significant difference in progression to MS comparing different clinical types of CIS (p=0,039). Subtypes involving cerebral hemispheres with or without brainstem are most often associated with later MS. Conclusion: Significant differences exist between different clinical subtypes of CIS regarding progression to MS. Larger clinical studies could reveal characteristics of CIS that would better predict progression of CIS to MS.

Multiple Sclerosis Disease-Modifying Drugs in Children and Adolescents

The vast majority of drugs for the treatment of multiple sclerosis (MS) have been developed and approved for the adult patient population. The place of these drugs in the treatment of children remains undefined not only in Russia, but also throughout the world. Despite the fact that studies of new drugs in the pediatric patient population is part of the routine practice of large pharmaceutical agencies such as the FDA and the EMA, treatment recommendations FOR pediatric MS patients are based less on long-term systematized experience of clinical studies as on a professional consensus of international expert associations, particularly the International Pediatric Multiple Sclerosis Study Group (IPMSSG). Clinical trials include small numbers of patients of pediatric age, minor compared with the number of participants in adult studies. There is therefore a need to develop new assessments evidencing the efficacy and safety of drugs for the treatment of MS in children and adolescents. This article presents the views of the IPMSSG on the treatment of pediatric MS, taking account of the characteristics of the Russian legislation and experience of Russian specialists.

Pediatric Multiple Sclerosis in Tunisia: A Retrospective Study over 11 Years.

Introduction Pediatric multiple sclerosis (pMS) is a rare demyelinating disorder with an onset before the age of 18 years. In this study, we aimed to investigate the characteristics of pMS in Tunisian children. Patients and Methods We conducted a retrospective study over 11 years (2005–2016) including all patients diagnosed with pMS according to the International Pediatric Multiple Sclerosis Study Group (IPMSSG) criteria of 2012 and followed up in a tertiary care research center. Epidemiological, clinical, neuroimaging, laboratory, and therapeutic data were collected and analyzed. Results There were 21 patients. The male-female ratio was 1 : 3. Mean age at onset was 11 years (range: 3–17 years). Three patients had type 1 diabetes. Polyfocal presentation was preponderant (81%) with motor dysfunction in 57% of patients. Paroxysmal dystonia was noticed in 24%. All patients were diagnosed with relapsing-remitting form. Interferon beta was prescribed in 80% with a reduction of annual relapse rate. Conclusion The annual incidence of pMS in Tunisian children aged below 18 years could be estimated as 0.05 per 100,000. Singular features in our cohort were the frequent association with type 1 diabetes and the increased occurrence of dystonia. Greater awareness of pMS may be helpful to improve management strategies of children and their families.

An interpretation of consensus statements on diagnostic criteria for multiple sclerosis and demyelinating diseases of the central nervous system in children (2012 version)

The International Pediatric Multiple Sclerosis Study Group (IPMSSG) put forward the 2007 version of the diagnostic criteria for multiple sclerosis and other immune-mediated demyelinating diseases of the central nervous system in children in 2007 ("2007 version" for short). In 2012, IPMSSG proposed the new diagnostic criteria with reference to the latest research achievements of 150 members ("2012 version" for short). The 2012 version of the consensus statements covers the diagnostic criteria for acute disseminated encephalomyelitis, clinically isolated syndrome, neuromyelitis optica, and multiple sclerosis in children. As the two IPMSSG members in China, the authors give an interpretation of the 2012 version of the consensus statements with reference to related literature and clinical and scientific experience. The authors focus on how the 2012 version comprehensively and thoroughly elaborates on the clinical features, diagnostic criteria, influencing factors, and new ideas of acute demyelinating diseases of the central nervous system in children. These become more operable in clinical diagnosis and treatment of multiple sclerosis and other immune-mediated demyelinating diseases of the central nervous system in children.

International Pediatric MS Study Group Global Members Symposium report.

The International Pediatric Multiple Sclerosis Study Group held its inaugural educational program, "The World of Pediatric MS: A Global Update," in September 2014 to discuss advances and challenges in the diagnosis and management of pediatric multiple sclerosis (MS) and other neuroinflammatory CNS disorders. Highlights included a discussion on the revised diagnostic criteria, which enable the differentiation of MS, acute disseminated encephalomyelitis, neuromyelitis optica, and other neuroinflammatory disorders. While these criteria currently identify clinical and MRI features for a particular diagnosis, advances in biomarkers may prove to be useful in the future. An update was also provided on environmental factors associated with pediatric MS risk and possibly outcomes, notably vitamin D deficiency. However, optimal vitamin D intake and its role in altering MS course in children have yet to be established. Regarding MS outcomes, our understanding of the cognitive consequences of early-onset MS has grown. However, further work is needed to define the course of cognitive function and its long-term outcome in diverse patient samples and to develop strategies for effective cognitive rehabilitation specifically tailored to children and adolescents. Finally, treatment strategies were discussed, including a need to consider additional drug treatment options and paradigms (escalation vs induction), although treatment should be tailored to the individual child. Of critical importance, clinical trials of newer MS agents in children are required. Although our understanding of childhood MS has improved, further research is needed to have a positive impact for children and their families.

Pediatric demyelinating disorders

The field of pediatric-onset multiple sclerosis (MS) and other demyelinating diseases in childhood has advanced considerably since the publication of the last International Pediatric Multiple Sclerosis Study Group (IPMSSG)–sponsored Neurology ® supplement in 2007. Over the last decade, demyelinating diseases of the CNS in children, and MS in particular, have garnered considerable international focus, both in the clinical and research world but also in the lay press and public awareness. This coming of age resulted in an exponential increase in research efforts and publications, with more than 250 peer-reviewed publications on pediatric MS in the past 10 years. It has also crystallized national and international collaborations that are critical to transform the field. Contributors: IPMSSG Steering Committee Members: Maria Pia Amato: Department NEUROFARBA, Section Neurosciences, University of Florence, Italy; Brenda Banwell: The Children's Hospital of Philadelphia, Perelman School of Medicine, University of Pennsylvania, Philadelphia; Angelo Ghezzi, Divisione di Neurologia 2–Centro Studi Sclerosi Multipla, Ospedale di Gallarate, Gallarate, Italy; Rogier Q. Hintzen: Department of Neurology, MS Centre ErasMS, Neurology, Erasmus MC, Rotterdam, the Netherlands; Lauren B. Krupp: Lourie Center for Pediatric MS, Stony Brook Children's Hospital, Stony Brook University, New York; Kevin Rostasy: Department of Pediatric Neurology, Children's Hospital Datteln, University Witten/Herdecke, Germany; Silvia Tenembaum: Department of Neurology, National Pediatric Hospital Dr. Juan P. Garrahan. Ciudad de Buenos Aires, Argentina; Evangeline Wassmer: Department of Neurology, Birmingham Children's Hospital, UK; Emmanuelle Waubant: Pediatric MS Center, UCSF Benioff Children's Hospital, and Neurology Department, UCSF, San Francisco, CA. IPMSSG Coordinating Consultant: Jon Temme.

Disease-modifying drugs in pediatric patients with multiple sclerosis

The vast majority of therapies are being evaluated and introduced for the treatment of adult multiple sclerosis (MS). A role of these drugs in the management of pediatric MS has yet to be defined both in Russia and in the whole world. Despite the fact that today the study of new drugs in the pediatric population have included in routine practices of the big pharmaceutical agencies, such as FDA and EMA, recommendations for the treatment of pediatric patients with MS are based not so much on a long period of systematic clinical research, but on professional consensus of international expert associations, in particular, the International pediatric multiple sclerosis study group (IPMSSG). The clinical trials include the small number of patients which is not comparable to those conducted in adults. Therefore, there is a need for study designs for assessment of efficacy and safety of the drugs for MS treatment in children and adolescents. The authors present the IPMSSG concept on the treatment of pediatric MS taking into account peculiarities of the Russian legislation and experience of national experts.