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.