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Background Persons with multiple sclerosis (pwMS) experience walking impairments, characterized by decreased walking speeds. In healthy subjects, the self-selected walking speed is the energetically most optimal. In pwMS, the energetically most optimal walking speed remains underexposed. Therefore, this review aimed to determine the relationship between walking speed and energetic cost of walking (Cw) in pwMS, compared with healthy subjects, thereby assessing the walking speed with the lowest energetic cost. As it is unclear whether the Cw in pwMS differs between overground and treadmill walking, as reported in healthy subjects, a second review aim was to compare both conditions. Method PubMed and Web of Science were systematically searched. Studies assessing pwMS, reporting walking speed (converted to meters per second), and reporting oxygen consumption were included. Study quality was assessed with a modified National Heart, Lung and Blood Institute checklist. The relationship between Cw and walking speed was calculated with a second-order polynomial function and compared between groups and conditions. Results Twenty-nine studies were included (n = 1535 pwMS) of which 8 included healthy subjects (n = 179 healthy subjects). PwMS showed a similar energetically most optimal walking speed of 1.44 m/s with a Cw of 0.16, compared with 0.14 mL O2/kg/m in healthy subjects. The most optimal walking speed in treadmill was 1.48 m/s, compared with 1.28 m/s in overground walking with a similar Cw. Conclusion Overall, the Cw is elevated in pwMS but with a similar energetically most optimal walking speed, compared with healthy subjects. Treadmill walking showed a similar most optimal Cw but a higher speed, compared with overground walking.

Hanne Bielen reports no disclosures. Kyra Theunissen reports no disclosures.Lousin Moumdjian reports no disclosures. Clinical manifestation walking fatigability 2Johan Van Nieuwenhoven reports no disclosures.Bart Van Wijmeersch has received financial support/study grants and fees for speaking and serving on advisory boards from Bayer, Biogen, F. Hoffmann-La Roche Ltd, Genzyme/Sanofi, Merck Serono, Novartis and Teva.Raf Meesen reports no disclosures.Cintia Ramari reports no disclosures.