Objectives The aim of this study is to describe patients with unusual symptoms that were primary manifestations of multiple sclerosis (MS). Patients and methods We report 21 multiple sclerosis patients who presented unusual initial pictures (acute brachial pain n=4, headache n=6, ptosis n=1, oculomotor nerve palsy n=1, peripheral facial palsy n=1, throat pain n=1, hypoglossal nerve palsy n=1, visual field defect n=2, epilepsia n=2, and coma n=2) as the first manifestations in the absence of other obvious symptoms or signs. Results Investigations demonstrated changes highly suggestive of multiple sclerosis on magnetic resonance imaging, cerebrospinal fluid analysis and electrophysiological tests. All cases completely or partially recovered after high-dose corticosteroid therapy. These patients have been followed up for 5 years. Conclusion In this study, we discuss possible correlations between clinical disturbances and neuroradiological abnormalities and show some rare or previously undescribed manifestations in multiple sclerosis.