Clinically isolated syndrome (CIS) is a term that describes a first clinical episode with features suggestive of multiple sclerosis (MS). It usually occurs in young adults and affects optic nerves, the brainstem, or the spinal cord. Although patients usually recover from their presenting episode, CIS is often the first manifestation of MS.

Most Common Clinically Isolated Syndrome Presentations (Miller et al., 2008)

Optic Neuritis	Brainstem	Spinal Cord
Typical for MS:	Typical for MS:	Typical for MS:
Unilateral visual loss, orbital pain, afferent pupillary defect, retrobulbar or mild disc swelling, visual loss does not progress beyond two weeks	Internuclear ophthalmoplegia, 6th nerve palsy, multifocal signs (e.g., facial sensory loss, vertigo, hearing loss, ataxia, dysarthria)	Evolution over hours to days, partial myelitis, Lhermitte’s sign, partial Brown-Séquard, spontaneous remission
Brain and Spinal MRI	Brain and Spinal MRI	Brain and Spinal MRI
Within 5 years: Normal brain MRI  20% risk of conversion to clinically definite MS (CDMS) Abnormal brain MRI (> 2 lesions consistent with demyelination   80-90% risk of conversion to CDMS, depending on CIS presentation)

The most notable risk factors for MS are clinically silent MRI lesions and CSF oligoclonal bands; weak or uncertain risk factors include vitamin D deficiency, Epstein-Barr virus infection, smoking, HLA genes, and miscellaneous immunological abnormalities (Miller et al., 2012). Disease-modifying treatments delay the conversion of CIS to MS.