High burden of poor prognostic factors at first presentation in treatment-naïve relapsing multiple sclerosis: Real-world evidence from a large Egyptian cohort.

BACKGROUND: Early clinical and radiological characteristics at presentation provide important prognostic information in multiple sclerosis (MS). However, baseline disease severity in treatment-naïve patients from Middle Eastern and North African populations remains scarce.

OBJECTIVE: To quantify poor prognostic factors at first presentation and identify independent predictors of early disability in a large Egyptian MS cohort.

METHODS: We retrospectively analyzed 1095 consecutive treatment-naïve patients with relapsing MS presenting for the first time to a tertiary referral center. Demographic, clinical, and MRI variables at baseline were collected. Established poor prognostic factors were predefined, and the cumulative burden per patient was calculated. Moderate to severe disability was defined as Expanded Disability Status Scale (EDSS) ≥3. Independent predictors were evaluated using multivariable logistic regression.

RESULTS: A total of 1095 patients were analyzed (72.6% female; median age 37 years; median onset age 26 years). The median diagnostic delay was 9 years. At presentation, 39.3% had EDSS ≥3. Poor prognostic features were common, including pyramidal involvement (38.8 %), short inter-attack interval (42.0%), ≥2 relapses during the first year (34.7%), infratentorial lesions (60.1%), and spinal lesions (61.6%). Overall, 82.9% of patients exhibited ≥4 poor prognostic factors and 50.8% had ≥6. On multivariable analysis, age at onset >40 years (OR 1.04), pyramidal involvement (OR 1.72), cerebellar involvement (OR 1.81), infratentorial lesions (OR 1.49), and T1 black holes (OR 1.76) independently predicted EDSS ≥3 (all p < 0.05). Sex, smoking, relapse frequency, and gadolinium enhancement were not independently associated with disability.

CONCLUSIONS: Treatment-naïve patients presenting to our tertiary MS center frequently exhibited multiple unfavorable prognostic features and substantial disability. However, the prolonged diagnostic delay observed in this cohort likely reflects referral patterns specific to this tertiary center and should not be interpreted as representative of national MS diagnostic timelines in Egypt. Early motor pathway involvement and MRI markers of tissue damage, rather than inflammatory activity alone, were the principal determinants of disability at presentation.