Fifteen studies, including approximately 590 pediatric patients, were analyzed. ADEM showed the greatest cognitive burden: 39.5% required educational support post-onset versus 8.6% pre-onset (p < 0.05), and it independently predicted academic difficulty (78.9% vs. 41.3%, p = 0.02); deep grey matter involvement occurred in 86.6%. ON showed better visual recovery in children than adults (73.3% vs. 31.0%, p = 0.001) despite similar retinal nerve fiber layer atrophy (~63 µm) and had the highest relapse rates. TM conferred the highest disability risk: each one-point increase in nadir Expanded Disability Status Scale (EDSS) was associated with a 6.7-fold increase in odds of long-term disability (OR 6.65, 95% CI 1.33-33.26, p = 0.021), with persistent bladder dysfunction in 28%. Encephalitis was associated with higher epilepsy rates (18.2% vs. 1.4%, p = 0.003) and longer time to steroid initiation. Early immunotherapy initiated within 7 days reduced relapse risk significantly (OR 0.15, 95% CI 0.03-0.61, p = 0.009).