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Abstract This study was done to measure the level of sNfL in patients with MS and assess if it differed from the control group, and how it can relate to the other disease’s parameters in patients attending the neurology outpatient clinics at Suez Canal University Hospital. Sixty-two subjects were divided into two equal groups. The MS group of thirty-one subjects aged from 18 to 48 years and fulfilling the diagnosis of MS according to the 2017 revised McDonald’s criteria (Thompson et al., 2018). Subjects who had CIS, a history of, or showed evidence of other neurological disorders or psychiatric disorders were excluded from the cohort. All the selected MS patients underwent MRI examination and serum collection to assess NfL levels after a complete medical history and clinical examination were done. The median disease duration at the time of the interview was 4 years and the mean age of disease onset was 23.76 years which is younger than the age of onset in the west and the other MENA regions. Optic Neuritis (ON) was the most common 1st clinical presentation in our subjects (51.5%) and the most common type of clinical relapse accounting for 33.75% of the total relapses. sNfL levels of MS subjects were markedly high when compared to the control group (p <0.001), and patients with SPMS had higher levels than those with RRMS (p <0.001). The presence of infratentorial lesions on brain MRI was associated with higher levels of sNfL (p= 0.001) than those with lesions in other brain territories, and the presence of enhanced lesions on cervical MRI was also associated with high sNfL levels (p= 0.005). The multivariable regression analysis showed that an SPMS |