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Prognostication and contemporary management of clinically isolated syndrome
  1. Christopher Martin Allen1,
  2. Ellen Mowry2,
  3. Mar Tintore3,4,
  4. Nikos Evangelou1
  1. 1 Department of Clinical Neurology, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK
  2. 2 Neurology, Johns Hopkins University, Baltimore, Maryland, USA
  3. 3 Servei de Neurologia-Neuroimmunologia, Centre d’Esclerosi Múltiple de Catalunya, (Cemcat), Vall d'Hebron University Hospital, Barcelona, Spain
  4. 4 Multiple Sclerosis Centre of Catalonia, Vall d'Hebron University Hospital, Barcelona, Spain
  1. Correspondence to Dr Christopher Martin Allen, Department of Clinical Neurology, Division of Clinical Neuroscience, University of Nottingham School of Medicine, Nottingham, UK; christopher.allen{at}


Clinically isolated syndrome (CIS) patients present with a single attack of inflammatory demyelination of the central nervous system. Recent advances in multiple sclerosis (MS) diagnostic criteria have expanded the number of CIS patients eligible for a diagnosis of MS at the onset of the disease, shrinking the prevalence of CIS. MS treatment options are rapidly expanding, which is driving the need to recognise MS at its earliest stages. In CIS patients, finding typical MS white matter lesions on the patient’s MRI scan remains the most influential prognostic investigation for predicting subsequent diagnosis with MS. Additional imaging, cerebrospinal fluid and serum testing, information from the clinical history and genetic testing also contribute. For those subsequently diagnosed with MS, there is a wide spectrum of long-term clinical outcomes. Detailed assessment at the point of presentation with CIS provides fewer clues to calculate a personalised risk of long-term severe disability.

Clinicians should select suitable CIS cases for steroid treatment to speed neurological recovery. Unfortunately, there are still no neuroprotection or remyelination strategies available. The use of MS disease modifying therapy for CIS varies among clinicians and national guidelines, suggesting a lack of robust evidence to guide practice. Clinicians should focus on confirming MS speedily and accurately with appropriate investigations. Diagnosis with CIS provides an opportune moment to promote a healthy lifestyle, in particular smoking cessation. Patients also need to understand the link between CIS and MS. This review provides clinicians an update on the contemporary evidence guiding prognostication and management of CIS.

  • multiple sclerosis
  • MRI
  • CSF

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  • Contributors CMA, EM, MT and NE designed the review. CMA drafted the work and CMA, EM, MT and NE revised it for critically important intellectual content and approved the version published. NE is responsible for the overall content as guarantor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests EM reports research support from Biogen (MS PATHS and investigator-initiated studies) and Sanofi-Genzyme for investigator-initiated studies, serving as site principal investigator for a Sun Pharma study, free medication from Teva Neuroscience for use in a clinical trial, for which she is principal investigator, and royalties for editorial duties from UpToDate. MT has received compensation for consulting services and speaking honoraria from Almirall, Bayer Schering Pharma, Biogen-Idec, Genzyme, Merck-Serono, Novartis, Roche, Sanofi-Aventis, Viela Bio and Teva Pharmaceuticals and MT is coeditor of Multiple Sclerosis Journal-ETC. NE has received compensation for consulting services and speaking honoraria from Biogen, Merck, Novartis and Roche.

  • Patient consent for publication Not required.

  • Provenance and peer review Commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.