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Clinically Isolated Syndrome


Clinically isolated syndrome (CIS) is a term that describes a first clinical episode of a disease that shows characteristics of inflammatory demyelination that could be MS but has yet to fulfill criteria of dissemination in time (Lublin et al., 2014; Miller et al., 2005). 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 CIS Presentations and Risk Factors for Clinically Definite MS (Miller et al 2012,)

Optic Neuritis

  • Unilateral reduced visual acuity
  • Orbital pain particularly with eye movement
  • Reduced color vision
  • Afferent pupillary defect
  • Retrobulbar or mild disc swelling


  • Bilateral internuclear ophthalmoplegia
  • Ataxia and gaze evoked nystagmus
  • 6th nerve palsy
  • Multi-focal symptoms
  • Facial sensory loss
  • Vertigo
  • Ataxia
  • Dysarthria

Spinal cord

  • Incomplete transverse myelitis
  • Positive Lhermitte’s sign
  • Sphincter symptoms
  • Asymmetric limb weakness
  • Symptom progression between 4 hours and 21 days.

Risk Factors for the conversion to clinically definite MS (CDMS) (Miller et al 2012; Ruet et al., 2011)

Important risk factors for the conversion to clinically definite MS (CDMS)

  • Presenting symptoms
  • Clinically silent MRI lesions
    • No lesions are associated with a 20% risk of conversion to CDMS
    • Abnormal MRI consistent with demyelination associated with 60-80% conversion to CDMS
  • CSF oligoclonal bands

Other risk factors

  • Vitamin D deficiency
  • History of Epstein-Barr virus infection
  • Smoking
  • HLA genes
  • Miscellaneous immunological abnormalities

Treatment of CIS (Miller et al., 2012:Ruet et al., 2011)

  • High dose glucocorticoids for acute symptoms
  • Disease-modifying treatments delay the conversion of CIS to MS.