Pediatric Multiple Sclerosis Patients Research Articles

Cognitive Impairment Is Related to Glymphatic System Dysfunction in Pediatric Multiple Sclerosis.

The aim of this study was to investigate whether, compared to pediatric healthy controls (HCs), the glymphatic system is impaired in pediatric multiple sclerosis (MS) patients according to their cognitive status, and to assess its association with clinical disability and MRI measures of brain structural damage. Sixty-five pediatric MS patients (females = 62%; median age = 15.5 [interquartile range, IQR = 14.5;17.0] years) and 23 age- and sex-matched HCs (females = 44%; median age = 14.1 [IQR = 11.8;16.2] years) underwent neurological, neuropsychological and 3.0 Tesla MRI assessment, including conventional and diffusion tensor imaging (DTI). We calculated the diffusion along the perivascular space (DTI-ALPS) index, a proxy of glymphatic function. Cognitive impairment (Co-I) was defined as impairment in at least 2 cognitive domains. No significant differences in DTI-ALPS index were found between HCs and cognitively preserved (Co-P) pediatric MS patients (estimated mean difference [EMD] = -0.002 [95% confidence interval = -0.069; 0.065], FDR-p = 0.956). Compared to HCs and Co-P patients, Co-I pediatric MS patients (n = 20) showed significantly lower DTI-ALPS index (EMD = -0.136 [95% confidence interval = -0.214; -0.058], FDR-p ≤ 0.004). In HCs, no associations were observed between DTI-ALPS index and normalized brain, cortical and thalamic volumes, and normal-appearing white matter (NAWM) fractional anisotropy (FA) and mean diffusivity (MD) (FDR-p ≥ 0.348). In pediatric MS patients, higher brain WM lesion volume (LV), higher NAWM MD, lower normalized thalamic volume, and lower NAWM FA were associated with lower DTI-ALPS index (FDR-p ≤ 0.016). Random Forest selected lower DTI-ALPS index (relative importance [RI] = 100%), higher brain WM LV (RI = 59.5%) NAWM MD (RI = 57.1%) and intelligence quotient (RI = 51.3%) as informative predictors of cognitive impairment (out-of-bag area under the curve = 0.762). Glymphatic system dysfunction occurs in pediatric MS, is associated with brain focal lesions, irreversible tissue loss accumulation and cognitive impairment. ANN NEUROL 2024.

Neuroimaging characterization of multiple sclerosis lesions in pediatric patients: an exploratory radiomics approach.

Multiple sclerosis (MS), a chronic inflammatory immune-mediated disease of the central nervous system (CNS), is a common condition in young adults, but it can also affect children. The aim of this study was to construct radiomic models of lesions based on magnetic resonance imaging (MRI, T2-weighted-Fluid-Attenuated Inversion Recovery), to understand the correlation between extracted radiomic features, brain and lesion volumetry, demographic, clinical and laboratorial data. The neuroimaging data extracted from eleven scans of pediatric MS patients were analyzed. A total of 60 radiomic features based on MR T2-FLAIR images were extracted and used to calculate gray level co-occurrence matrix (GLCM). The principal component analysis and ROC analysis were performed to select the radiomic features, respectively. The realized classification task by the logistic regression models was performed according to these radiomic features. Ten most relevant features were selected from data extracted. The logistic regression applied to T2-FLAIR radiomic features revealed significant predictor for multiple sclerosis (MS) lesion detection. Only the variable "contrast" was statistically significant, indicating that only this variable played a significant role in the model. This approach enhances the classification of lesions from normal tissue. Our exploratory results suggest that the radiomic models based on MR imaging (T2-FLAIR) may have a potential contribution to characterization of brain tissues and classification of lesions in pediatric MS.

INTERVENTIONS AFFECTING PROGNOSIS AND QUALITY OF LIFE IN PEDIATRIC MULTIPLE SCLEROSIS: A SYSTEMATIC REVIEW

Introduction: Multiple sclerosis, autoimmune disease of the central nervous system primarily affecting young adults. The number of individuals suffering from multiple sclerosis under the age of 18 is gradually increasing. Early interventions in the form of pharmacotherapy have proven to be beneficial in reducing the severity of disease and thereby preventing disability. Furthermore, cognitive impairment affecting working memory, attention, and other domains is concerning in children. Methodology: We identified papers by searching various electronic databases (PubMed, Google Scholar, Europe PMC, Scopus, Web of Science). Search terms included: Pediatric multiple sclerosis OR pediatric MS AND interventions AND prognosis OR disease progression OR disability OR quality of life OR QoL. Papers were included in this review if they were published in English, referenced interventions and their effects on quality of life of the patients, and included pediatric-onset multiple sclerosis as a primary population. Results: Seventeen papers were identified via the literature search that addressed interventions made in the field of pediatric multiple sclerosis and their effects on the quality of life of the patients. The current study extracted data from a diverse range of articles focusing on various aspects of pediatric-onset multiple sclerosis (POMS) treatment, outcomes, and associated factors. The data provided valuable insights into the clinical characteristics, treatment approaches, and quality of life considerations for POMS patients. Discussion: Interventions include first line drugs (interferon beta-1a and glatiramer acetate) and disease modifying therapies like fingolimod, teriflunomide, natalizumab and rituximab. Potential modifiable factors like breastfeeding, vitamin D levels, exercise and diet were identified. CSF Neurofilament levels and various inflammatory genes are helpful in diagnosis. Conclusion: The data extraction from diverse studies on POMS shed light on various treatment approaches, disease progression markers and psychosocial factors. The findings underscore the importance of early intervention, tailored treatment strategies, and multidisciplinary care to enhance outcomes for pediatric MS patients.

Assessing Psychiatric Symptoms in Pediatric Multiple Sclerosis Patients

Assessing Psychiatric Symptoms in Pediatric Multiple Sclerosis Patients

Pretreatment Neurofilament Light Chain Serum Levels, Early Disease Severity, and Treatment Response in Pediatric Multiple Sclerosis.

High disease activity and frequent therapy failure in pediatric multiple sclerosis (MS) make prognostic biomarkers urgently needed. We investigated whether serum neurofilament light chain (sNfL) levels in treatment-naive pediatric patients with MS are associated with early disease severity and indicate treatment outcomes. A retrospective cohort study of patients seen in the Göttingen Center for MS in Childhood and Adolescence, Germany. Inclusion criteria were MS diagnosis according to the McDonald criteria, MS onset <18 years, and available pretreatment serum sample. sNfL levels were analyzed using a single-molecule array assay. Associations with clinical and MRI evidence of disease severity at sampling were evaluated using the Spearman correlations and nonparametric tests for group comparisons. Correlations between pretreatment sNfL and annualized relapse and new T2 lesion rate on first-line therapy, and odd ratios for switch to high-efficacy therapy were assessed. A total of 178 patients (116 women [65%]) with a mean sampling age of 14.3 years were included in the study. Pretreatment sNfL levels were above the ≥90th percentile reported for healthy controls in 80% of patients (median 21.1 pg/mL) and correlated negatively with age, but no correlation was seen with sex, oligoclonal band status, or body mass index. High pretreatment sNfL levels correlated significantly with a high number of preceding relapses, a shorter first interattack interval, a high T2 lesion count, and recent gadolinium-enhancing lesions. Of interest, sNfL levels reflected more strongly MRI activity rather than clinical activity. Pretreatment sNfL levels also correlated significantly with the relapse rate and occurrence of new/enlarging T2 lesions while on first-line injectable therapy. Odds of future therapy escalation increased from 0.14 for sNfL below 7.5 pg/mL to 6.38 for sNfL above 15 pg/mL. In patients with a recent relapse, higher sNfL levels were associated with poorer recovery 3 months after attack. The results of this study have 3 important implications: First, pretreatment sNfL levels are a valuable biomarker for underlying disease activity in pediatric patients with MS. Second, pretreatment sNfL levels in pediatric patients with MS have a predictive value for the response to first-line therapy and the necessity of future therapy escalation. Third, high sNfL levels during a relapse are associated with poor recovery in this age group.

Fingolimod-related atrioventricular block in paediatric age group with multiple sclerosis: two case reports.

Multiple sclerosis is a chronic inflammatory and demyelinating disease of the central nervous system, usually seen in young adults. Early onset of multiple sclerosis at age younger than 18 years is called paediatric multiple sclerosis. Unlike adult multiple sclerosis, paediatric multiple sclerosis causes morbidity at earlier ages and often progresses in a relapsing-remitting form. Although fingolimod is an effective drug used as a disease-modifiying therapy agent in relapsing-remitting paediatric multiple sclerosis patients, it can cause dysryhthmia in the early period after first dose. Our first case is a 14-year-old girl with relapsing-remitting paediatric multiple sclerosis patients who was started to take fingolimod treatment. In the fifth hour of the follow-up, asymptomatic bradycardia was seen and the electrocardiogram was consistent with first-degree atrioventricular block. Her rhythm got spontaneously normal after 12 hours. Second case was 13 years old girl. Steroid treatment was started after her first paediatric multiple sclerosis attack. Despite treatment, she had a second attack 2 weeks after the first attack. Therefore, the neurologist switched to fingolimod therapy. Second-degree atrioventriculer block developed after 4 hours from the initiation of therapy. After 8 hours, rhythm regressed to first-degree atrioventricular block then returned to normal up to 13th hours of follow up. The aim of this article is to draw attention to dysrhythmia side effect of fingolimod which can be fatal. Therefore, the clinician must take precautions. Close cardiac rhythm monitoring is mandatory after the initiation fingolimod theraphy.

Choroid Plexus Enlargement in Pediatric Multiple Sclerosis: Clinical Relevance and Effect of Sex (P10-3.009)

<h3>Objective:</h3> We investigated choroid plexus (CP) volume in pediatric multiple sclerosis (MS) patients compared to matched healthy controls (HC), possible sex-related effect, and the associations with clinical and structural MRI variables. <h3>Background:</h3> CP enlargement has been suggested as a reliable marker of neuroinflammation in adult MS patients, correlating with measures of brain structural damage and clinical disability. The presence and clinical relevance of CP enlargement in pediatric MS patients has not been evaluated yet. <h3>Design/Methods:</h3> Brain 3.0 T dual-echo and 3D T1-weighted sequences were identified retrospectively from 69 pediatric MS patients and 23 age- and sex-matched HC. CP volume was manually obtained from 3D T1-weighted scans by two expert raters. <h3>Results:</h3> CP segmentation was highly reproducible (intra-observer agreement: rater I=0.963, rater II=0.958; inter-observer agreement=0.968). Compared to HC, pediatric MS patients showed higher normalized CP volume (p&lt;0.001). When looking at sex-specific effect, both female and male pediatric MS patients showed higher normalized CP volume compared to sex-matched HC (females: p&lt;0.001; males: p=0.021), with a significant disease (MS vs HC) ‘ sex (females vs males) interaction (p=0.040). In MS patients, a higher normalized CP volume was significantly associated with higher brain T2-hyperintense white matter (WM) lesion volume (β=0.252, p=0.017), larger lateral ventricle volume (β=0.470, FDR p&lt;0.001), lower normalized brain volume (β=−0.413, FDR p=0.002) and lower normalized thalamic volume (β=0.291, FDR p=0.046). No associations with disease duration, EDSS score, normalized cortical and WM volumes were found (FDR p≥0.172). A significant effect of the disease in the negative association between normalized volumes of CP and thalami was found (FDR p=0.046). <h3>Conclusions:</h3> CP enlargement occurs in pediatric MS patients, suggesting its early involvement in the pathophysiology of the disease. The higher CP volume, that is found especially in female patients, supports the hypothesis of sex-related differences in the neuroinflammatory processes occurring already in pediatric MS patients. <b>Disclosure:</b> Monica Margoni has received research support from MAGNIMS. Dr. Gueye has nothing to disclose. Alessandro Meani has nothing to disclose. Elisabetta Pagani has nothing to disclose. Dr. Moiola has nothing to disclose. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla.

Functional Correlates of Intelligence Quotient and Cognitive Abilities Vary According to Maturation in Pediatric MS (P9-3.013)

<h3>Objective:</h3> To test maturation effects on neuropsychological profiles and resting state (RS) functional connectivity (FC) in cognitive and motor networks of pediatric patients with multiple sclerosis (MS). <h3>Background:</h3> Clinical and cognitive features of pediatric MS patients differ from adults. The effect of brain maturation on RS FC and its possible interaction with cognitive features has never been studied. <h3>Design/Methods:</h3> Seventy-six pediatric MS patients underwent a neuropsychological assessment of Wechsler-Intelligence-Scales for Intelligent Quotient (IQ), Semantic/Phonemic Verbal Fluency Test (SVFT/PVFT), Symbol Digit Modalities Test (SDMT), Coding Design (CD) and Block Design (BD) subtests, Trial Making Test (TMT-A/B). In 58 right-handed MS patients and 22 matched healthy controls (HC), RS FC within basal ganglia, executive, language, sensorimotor, and default-mode networks was estimated. Maturation effects were tested by splitting pediatric MS in those below the age of 16 years (B16) (n=46) and those above or equal 16 years (A16) (n=30). <h3>Results:</h3> Most patients (81.6%) achieved IQ scores within or above average values (median IQ=97.5). The highest rate of failure was observed in CD (21.1%), TMT-B (15.8%), TMT-A (10.5%), and SDMT (9.2%). Compared to HC, pediatric MS patients showed reduced RS FC in all networks, mainly involving the caudate nucleus and its connections with cingulate, prefrontal, and sensorimotor cortices. This effect was particularly relevant in younger patients (B16), where reduced basal ganglia, language and executive RS FC was associated with poorer cognitive performances (r range=0.37/0.48), while reduced cingulate RS FC was associated with a lower IQ (r=0.36). In older patients (A16), reduced language and executive RS FC was correlated with lower IQ and CD, BD and PVFT/SVFT scores (r range=0.42–0.67). However, A16 patients also presented increased executive, default-mode and language RS FC <i>vs</i> HC, which was detrimental on performance at the same tests (r range=−0.39/−0.62). <h3>Conclusions:</h3> Maturation significantly impacts on RS FC abnormalities and on their association with cognitive performances. <b>Disclosure:</b> Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BMS Celgene. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Ms. Cacciaguerra has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for BIOMEDIA. Dr. Curatoli has nothing to disclose. Carmen Vizzino has nothing to disclose. Monica Margoni has received research support from MAGNIMS. Paola Valsasina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACCMED. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA).

Longitudinal Cognitive Screening Findings in Pediatric MS vs. Pediatric Controls and Adult MS in a Multi-center Cohort (S31.008)

<h3>Objective:</h3> To compare longitudinal cognitive performance between pediatric patients with relapsing remitting multiple sclerosis (RRMS), pediatric healthy controls (HC), and adult patients with RRMS. <h3>Background:</h3> Pediatric MS affects the brain at an important time of development in children and teenagers. Studies of cognition in these patients have provided mixed results. <h3>Design/Methods:</h3> Consecutively eligible pediatric MS patients (n=71), pediatric healthy peers (n=99), and adult MS patients (n=66) enrolled across seven centers from the US Network of Pediatric MS Centers underwent a cognitive screening battery at baseline and 1.5–3.5 years later. Baseline cognitive test results were previously reported. Longitudinal findings on the individual measures of the BICAMS (Brief International Cognitive Assessment for MS) and Cogstate Brief Battery (CBB) were analyzed using z-scores based on available normative data. <h3>Results:</h3> 87% of pediatric MS patients, 82% of pediatric controls, and 73% of adult MS patients returned for follow-up after a mean of 2.15 years. Those who returned had baseline demographic characteristics similar to those who did not return. The mean change in z-scores at the end of the study for the pediatric MS patients did not differ from pediatric controls on the BICAMS or Cogstate batteries: Symbol Digit Modalities Test (SDMT) (−0.4 vs. 0.1, p=0.20); Rey Auditory Verbal Learning Test (RAVLT) (−0.6 vs. −0.6, p=0.90); and the Brief Visuospatial Memory Test-Revised (BVMT-R) (−0.0 vs. 0.1, p=0.52). Pediatric vs. adult cases showed no differences in mean change in z-scores, except on the RAVLT, where both pediatric MS and pediatric controls declined to a greater degree than adults with MS (p=0.007). <h3>Conclusions:</h3> This study showed relative stability in cognitive performance among pediatric and adult cases of RRMS and pediatric controls. It is reassuring that many with pediatric MS show preserved cognitive function relative to healthy peers early in their short-term disease course. <b>Disclosure:</b> Dr. O’Neill has nothing to disclose. Dr. Charvet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Johnson &amp; Johnson. Dr. Charvet has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Springer Healthcare. Dr. Charvet has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for YBrain. Dr. Charvet has stock in Johnson&amp;Johnson. Michael Waltz has nothing to disclose. Dr. Casper has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Aperta Biosciences. Dr. Casper has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for After Hours Medical. The institution of Dr. Casper has received research support from NIH. The institution of Dr. Casper has received research support from The National Multiple Sclerosis Society. The institution of Dr. Casper has received research support from Roche. Allan George has nothing to disclose. The institution of Dr. Benson has received research support from ROHHAD Fight, Inc. The institution of Dr. Benson has received research support from Shore Foundation. The institution of Dr. Benson has received research support from Alexion Pharmacuticals. The institution of Dr. Benson has received research support from Biogen, Inc. The institution of Dr. Benson has received research support from NIH. Dr. Benson has received personal compensation in the range of $0-$499 for serving as a consultant with MA Department of public health. Dr. Benson has received personal compensation in the range of $5,000-$9,999 for serving as a consultant with National vaccine injury compensation program. The institution of Dr. Gorman has received research support from Pfizer. The institution of Dr. Gorman has received research support from Roche / Genetech . Dr. Goyal has received stock or an ownership interest from IBM. The institution of Dr. Goyal has received research support from NIH. Dr. Goyal has received personal compensation in the range of $0-$499 for serving as a Conference attendee with Capital Medical University, Shandong Madic Technology Co Ltd, Tancheng Talent Office. The institution of Dr. Mar has received research support from NIH. An immediate family member of Dr. Ness has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Jan One. The institution of Dr. Ness has received research support from Chugai/Roche. The institution of Dr. Ness has received research support from National Multiple Sclerosis Society. The institution of an immediate family member of Dr. Ness has received research support from NIH. An immediate family member of Dr. Ness has received publishing royalties from a publication relating to health care. The institution of Dr. Schreiner has received personal compensation in the range of $500-$4,999 for serving as a Consultant for CDC. Dr. Schreiner has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Schreiner has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Mary C Bush, LLC. The institution of Dr. Schreiner has received research support from Roche Genentech. Dr. Waubant has received personal compensation in the range of $500-$4,999 for serving as a Consultant for emerald pharmaceuticals. Dr. Waubant has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for elsevier. The institution of Dr. Waubant has received research support from NIH. The institution of Dr. Waubant has received research support from NMSS. The institution of Dr. Waubant has received research support from PCORI. The institution of Dr. Waubant has received research support from Race to Erase MS. The institution of Dr. Waubant has received research support from Roche. The institution of Dr. Waubant has received research support from Biogen. The institution of Dr. Waubant has received research support from Department of Defense. Dr. Waubant has received publishing royalties from a publication relating to health care. Dr. Weinstock-Guttman has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EMD Serono. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Abbvie. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genzyme &amp;Sanofi. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen . Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bayer. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Horizon. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Weinstock-Guttman has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Dr. Weinstock-Guttman has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Janssen. Dr. Weinstock-Guttman has received personal compensation in the range of $0-$499 for serving as a Reviewer with NIH. Yolanda Wheeler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Celgene Corporation. Yolanda Wheeler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Banner Life Sciences. Yolanda Wheeler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Mutliple Sclerosis Association of America. Yolanda Wheeler has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Multiple Sclerosis Association of America. The institution of Yolanda Wheeler has received research support from National MS Society. The institution of Yolanda Wheeler has received research support from National MS Society. Dr. Aaen has nothing to disclose. Dr. Abrams has nothing to disclose. Dr. Chitnis has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. Dr. Chitnis has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche-Genentech. Dr. Chitnis has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Academic CME. The institution of Dr. Chitnis has received research support from Novartis. The institution of Dr. Chitnis has received research support from Sanofi. The institution of Dr. Chitnis has received research support from Octave. Dr. Lotze has received personal compensation in the range of $5,000-$9,999 for serving as an Expert Witness for Department of Justice VICP. The institution of Dr. Lotze has received research support from NIH. The institution of Dr. Lotze has received research support from National MS Society. The institution of Dr. Lotze has received research support from Sarepta Therapeutics. The institution of Dr. Lotze has received research support from PTC THERAPEUTICS. The institution of Dr. Lotze has received research support from Avexis. Dr. Lotze has received publishing royalties from a publication relating to health care. Dr. Rensel has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Rensel has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cycle Pharma. Dr. Rensel has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for biogen. Dr. Rensel has stock in Brain Ops Group LLC. Dr. Rensel has stock in Brain Fresh LLC . The institution of Dr. Rensel has received research support from NMSS. The institution of Dr. Rensel has received research support from Biogen. The institution of Dr. Rensel has received research support from genentech. Dr. Rodriguez has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Rose has received research support from National Multiple Sclerosis Society. The institution of Dr. Rose has received research support from Guthy Jackson Charitable Foundation. The institution of Dr. Rose has received research support from NIH . The institution of Dr. Rose has received research support from VA. The institution of Dr. Rose has received research support from Biogen. The institution of Dr. Rose has received research support from Friends of MS. Dr. Rose has received intellectual property interests from a discovery or technology relating to health care. Dr. Shukla has nothing to disclose. Dr. Tillema has nothing to disclose. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Janssen. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Gerson Lerhman. Dr. Krupp has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for medscape. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for NeuroLive. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Krupp has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sanofi. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as an officer or member of the Board of Directors for Cleveland Clinic. Dr. Krupp has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for MCIC. The institution of Dr. Krupp has received research support from Biogen. The institution of Dr. Krupp has received research support from National Multiple Sclerosis Society. Dr. Krupp has received intellectual property interests from a discovery or technology relating to health care.

Identification of Neuropsychological Phenotypes in Pediatric Multiple Sclerosis Using Unsupervised Machine Learning (P12-9.001)

<h3>Objective:</h3> To identify cognitive phenotypes in pediatric multiple sclerosis (MS) using an unsupervised machine learning approach. <h3>Background:</h3> Recent studies identified distinct cognitive phenotypes in adult MS patients using unsupervised machine learning approaches. <h3>Design/Methods:</h3> Fifty-three pediatric MS patients underwent clinical examination including Expanded Disability Status Scale (EDSS) to assess global disability. A comprehensive neuropsychological battery (Selective Reminding Test, Spatial Recall Test, Trail Making Test, Symbol Digit Modalities Test, Semantic verbal fluency test and Phonemic verbal fluency test) was administered to all patients. Raw scores of each test were converted to z-scores according to normative data. Cognitive tests z-scores were included in a k-means cluster analysis to identify cognitive phenotypes. Between-group comparisons of demographic, clinical and cognitive variables were computed using linear regression models or nonparametric tests as appropriate. Statistical significance was corrected for multiple comparisons (Bonferroni method). <h3>Results:</h3> In our sample, median age was 15.9 years (interquartile range [IQR] 13.6 – 16.8), 68% (36 patients) were girls and the mean disease duration was 1.8±1.7 years. Cluster analysis identified three cognitive phenotypes: preserved cognition (27 patients [51%]), mild verbal memory/semantic fluency involvement (19 patients [36%]) and severe multidomain involvement (7 patients [13%]). Across groups, there were no significant differences in age, sex and disease duration. Lower EDSS scores were found in patients with preserved cognition (median EDSS 1.0 [IQR 1.0 – 1.0]) than patients with mild verbal memory/semantic fluency involvement (median EDSS 1.5 [IQR 1.0 – 2.0]; p=0.01) and patients with severe multidomain involvement (median EDSS 2.0 [IQR 1.25 – 2.75]; p=0.004). <h3>Conclusions:</h3> Pediatric MS patients present with distinct cognitive phenotypes ranging from preserved cognition to severe multidomain involvement. Cognitive phenotypes are not associated with age, sex and disease duration. Patients with preserved cognition are characterized by low global disability. <b>Disclosure:</b> Damiano Mistri has nothing to disclose. Monica Margoni has received research support from MAGNIMS. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Alessandro Meani has nothing to disclose. Carmen Vizzino has nothing to disclose. Dr. Moiola has nothing to disclose. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla.

The Use of Ocrelizumab in Pediatric Multiple Sclerosis Patients in the United Arab Emirates: A Retrospective Study

The Use of Ocrelizumab in Pediatric Multiple Sclerosis Patients in the United Arab Emirates: A Retrospective Study

Reliability and Validity of the Arabic Version of Brief International Cognitive Assessment for Multiple Sclerosis in Egyptian Pediatric Multiple Sclerosis Patients

Reliability and Validity of the Arabic Version of Brief International Cognitive Assessment for Multiple Sclerosis in Egyptian Pediatric Multiple Sclerosis Patients

Bilateral ptosis with ophthalmoplegia externa in paediatric onset multiple sclerosis: A case report

Paediatric onset multiple sclerosis (POMS) patients usually present with a diminution of vision pertaining to optic neuritis and experience a more aggressive disease onset with disabling clinical symptoms, a polyfocal presentation at disease onset, and a higher relapse rate early in the disease course. We are reporting a unique presentation of bilateral ptosis with external ophthalmoplegia in a patient of a 17-year-old female patient who came with chief complaint of drooping of lids in both eyes for 3 years. Complete ophthalmic and systemic examination was done. Patient was diagnosed as MS according to the revised Mcdonald criteria and was given Methylprednisolone Pulse therapy. We concluded that acquired bilateral ptosis with ophthalmoplegia externa should be given special attention to rule out systemic associations. Timely diagnosis and early management of multiple sclerosis in the pediatric age group with DMT may reduce relapse frequency and functional disability.

Re-examining the characteristics of pediatric multiple sclerosis in the era of antibody-associated demyelinating syndromes.

The discovery of anti-myelin oligodendrocyte glycoprotein (MOG)-IgG and anti-aquaporin 4 (AQP4)-IgG and the observation on certain patients previously diagnosed with multiple sclerosis (MS) actually have an antibody-mediated disease mandated re-evaluation of pediatric MS series. To describe the characteristics of recent pediatric MS cases by age groups and compare with the cohort established before 2015. Data of pediatric MS patients diagnosed between 2015 and 2021 were collected from 44 pediatric neurology centers across Türkiye. Clinical and paraclinical features were compared between patients with disease onset before 12 years (earlier onset) and ≥12 years (later onset) as well as between our current (2015-2021) and previous (<2015) cohorts. A total of 634 children (456 girls) were enrolled, 89 (14%) were of earlier onset. The earlier-onset group had lower female/male ratio, more frequent initial diagnosis of acute disseminated encephalomyelitis (ADEM), more frequent brainstem symptoms, longer interval between the first two attacks, less frequent spinal cord involvement on magnetic resonance imaging (MRI), and lower prevalence of cerebrospinal fluid (CSF)-restricted oligoclonal bands (OCBs). The earlier-onset group was less likely to respond to initial disease-modifying treatments. Compared to our previous cohort, the current series had fewer patients with onset <12 years, initial presentation with ADEM-like features, brainstem or cerebellar symptoms, seizures, and spinal lesions on MRI. The female/male ratio, the frequency of sensorial symptoms, and CSF-restricted OCBs were higher than reported in our previous cohort. Pediatric MS starting before 12 years was less common than reported previously, likely due to exclusion of patients with antibody-mediated diseases. The results underline the importance of antibody testing and indicate pediatric MS may be a more homogeneous disorder and more similar to adult-onset MS than previously thought.

A new look at cognitive functioning in pediatric MS

Objective: Cognitive involvement in pediatric multiple sclerosis (MS) relative to adult MS is less defined. This study advances our understanding by measuring cognitive performances in pediatric MS, adult MS, and pediatric healthy controls. Methods: Consecutive relapsing pediatric MS participants from the United States Network of Pediatric MS Centers were compared with pediatric healthy controls and adults with relapsing MS. Participants were compared on two screening batteries: the Brief International Cognitive Assessment for MS and the Cogstate Brief Battery. Results were transformed to age-normative z scores. Results: The pediatric groups (MS vs. Healthy Controls) did not differ on either battery’s composite mean score or individual test scores (ps > 0.32), nor in the proportions impaired on either battery, Brief International Cognitive Assessment for MS (26% vs. 24%, p = 0.83); Cogstate Brief Battery (26% vs. 32%, p = 0.41). The pediatric versus adult MS group even after controlling for differences in disease duration performed better on the Brief International Cognition Assessment for MS composite (p = 0.03), Symbol Digit Modalities Test (p = 0.02), Rey Auditory Verbal Learning Test (p = 0.01), and Cogstate choice reaction time (p < 0.001). Conclusion: Pediatric MS patients do not differ from healthy pediatric controls on cognitive screens but perform better than adults with MS.

Cognitive impairment in paediatric onset multiple sclerosis and its relation to thalamic volume and cortical thickness of temporal lobe by magnetic resonance imaging

BackgroundPediatric onset multiple sclerosis (POMS), defined as an age at onset younger than 18 years, which occurs in 5% of patients with MS. cognitive dysfunction is one of the prominent disabling sequelae of Multiple sclerosis. Brain volumetric studies by magnetic resonance images revealed the decline of whole and regional brain volumes along the disease course. This work aimed to investigate the relationship between cognitive impairment in pediatric MS patients with thalamic atrophy and cortical thickness of temporal lobe. This study included 50 patients who were diagnosed as POMS and 50 healthy control participants matched for age and sex. Both groups were compared for volumetric measurements of thalamic volumes and temporal lobes cortical thickness using a computerized program called FreeSurfer.MS group was evaluated for cognitive dysfunction using Arabic version of fifth edition of Standford–Benit test. A correlation between volumetric results and neuropsychological evaluation of MS group was done.ResultsOur study showed that the MS group has the lowest value regarding their thalamic volumes and their cortical thickness of temporal lobes in relation to the healthy control group, while there was a significant relation between cognitive impairment and decrease in thalamic volume and specific areas in cortical thickness, such as superior temporal thickness, middle temporal thickness, inferior temporal thickness, fusiform thickness and para hippocampal thickness of temporal lobe in pediatric onset MS patients.ConclusionsPOMS affects specific brain areas such as thalamus and cortical thickness of temporal lobes regarding their volume and thickness which influence the neuropsychological evaluation detected by Standford–Benit test.

Assessing treatment response in pediatric multiple sclerosis patients (P16-4.003)

Assessing treatment response in pediatric multiple sclerosis patients (P16-4.003)

Comparing Natural History of Early and Late Onset Pediatric Multiple Sclerosis.

This study was undertaken to describe and compare disease course and prognosis of early (ie, disease onset before age 11 years) and late (ie, disease onset after age 11 years) onset pediatric multiple sclerosis. Prospectively collected clinical information from Italian Multiple Sclerosis Register of 1993 pediatric multiple sclerosis patients, of whom 172 had early onset, was analyzed. Cox models adjusted for sex, baseline Expanded Disability Status Scale score, and disease-modifying treatments and stratified for diagnostic criteria adopted (Poser vs McDonald) were used to assess the risk of reaching irreversible Expanded Disability Status Scale scores of 3, 4, and 6, and conversion to secondary progressive phenotype in early versus late onset pediatric patients. Prognostic factors were also evaluated. A greater proportion of males, isolated brainstem involvement, and longer time interval between first and second clinical episode were observed in early versus late onset pediatric patients. Compared to late onset, early onset pediatric patients took longer from disease onset to convert to secondary progressive phenotype and to reach all disability milestones. Recovery from first demyelinating event, time to first relapse, annualized relapse rate during the first 3 years of disease, and disease-modifying treatment exposure were independent predictors for long-term disability in early onset pediatric patients. In late onset pediatric patients, isolated optic neuritis, multifocal symptoms, and progressive course at disease onset were additional predictors for long-term disability. These findings point toward the existence of a different natural history in early versus late onset pediatric multiple sclerosis patients. ANN NEUROL 2022;91:483-495.

Body size perceptions & diet modification in youth with multiple sclerosis

Background: Investigate the perceptions of pediatric multiple sclerosis (MS) patients regarding their body size and assess the feasibility of recruitment for a study of diet modification in this unique population. Methods: This cross-sectional study surveyed a cohort of 43 consecutive youth with MS. The survey queried participant demographics, clinical disease characteristics, body size perception, and opinions of diet modification Results: While over three quarters of surveyed participants were overweight/obese, 58% of these participants did not self-identify as such. A single participant was attempting a diet at the time of survey, but 88% of participants indicated interest in pursuing diet modification. BMI category did not impact an individual's willingness to pursue diet intervention; however, obese participants were more willing to participate in diet intervention for longer durations. Conclusion: A significant proportion of MS youth have an elevated BMI, yet the majority have the self-perception that they are not overweight or obese. Regardless of BMI, most youth with MS have an interest in pursuing diet modification in attempts to benefit their disease course.

Time to diagnosis in multiple sclerosis: Epidemiological data from the German Multiple Sclerosis Registry

Objective: To investigate the time to diagnosis in multiple sclerosis (MS) in Germany. Methods: Analysis of real-world registry data from the German Multiple Sclerosis Registry (GMSR) and performing a primary analysis in patients where month-specific registration of the dates of onset and diagnosis was available. Results: As of January 2020, data of a total of 28,658 patients with MS were extracted from the GMSR, with 9836 patients included in the primary analysis. The mean time to diagnosis was shorter following the introduction of the first magnetic resonance imaging (MRI)-based McDonald criteria in 2001. This effect was most pronounced in younger adults below the age of 40 years with relapsing onset multiple sclerosis (ROMS), with a decrease from 1.9 years in 2010 to 0.9 years in 2020, while unchanged in patients aged 40–50 years (1.4 years in 2010 and 1.3 years in 2020). In the limited number of paediatric onset MS patients, the time to diagnosis was longer and did not change (2.9 years). Conclusion: The current sensitive MRI-based diagnostic criteria have likely contributed to an earlier diagnosis of MS in Germany in younger adults aged 18–39 years with ROMS. Whether this translated to earlier initiation of disease-modifying treatment or had a beneficial effect on patient outcomes remains to be demonstrated.