What is Clinically Isolated Syndrome (CIS) in Multiple Sclerosis (MS)?

From the Guidelines

Clinically isolated syndrome (CIS) is the first clinical presentation of multiple sclerosis, characterized by a single episode of neurological symptoms caused by inflammation or demyelination in the central nervous system, and its diagnosis and management should be guided by the most recent MRI criteria, such as the 2010 McDonald criteria, as outlined in the MAGNIMS consensus guidelines 1.

Key Characteristics of CIS

• CIS is a single episode of neurological symptoms that lasts at least 24 hours and occurs in the absence of fever, infection, or other explanations.
• It affects one area of the central nervous system, such as the optic nerve, spinal cord, or brain stem.
• The risk of developing MS depends largely on whether MRI scans show additional lesions in the brain or spinal cord.

Diagnosis and Risk Assessment

• MRI scans are crucial in diagnosing CIS and assessing the risk of developing MS.
• If MRI shows multiple lesions, the risk of developing MS within 5-10 years is 60-80%, while those with normal MRIs have a 20% risk, as supported by the MAGNIMS consensus guidelines 1.
• Advanced MRI techniques, such as proton magnetic resonance spectroscopy, diffusion tensor imaging, and magnetization transfer imaging, may provide additional information on tissue damage and disease activity, but their sensitivity and specificity for diagnosis and differential diagnosis remain to be determined 1.

Treatment and Management

• Treatment for CIS often involves high-dose corticosteroids like methylprednisolone (1000mg IV daily for 3-5 days) to reduce inflammation and speed recovery from the acute episode.
• Disease-modifying therapies, such as interferon beta, glatiramer acetate, or newer agents, may be recommended for patients with high-risk CIS to delay progression to definite MS, as early treatment may reduce the frequency and severity of future attacks and slow disability progression.
• The use of advanced MRI techniques, such as those outlined in the Nature Reviews Neurology study 1, may help identify patients with an increased risk of developing severe disability and cognitive impairment, who may benefit from prompt, aggressive treatment.

From the FDA Drug Label

AVONEX is for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. TYSABRI is indicated as monotherapy for the treatment of relapsing forms of multiple sclerosis, to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Clinically Isolated Syndrome (CIS) in Multiple Sclerosis (MS) is not explicitly defined in the provided drug labels. The labels only mention that the drugs are indicated for the treatment of relapsing forms of MS, including CIS, but do not provide a definition of CIS itself 233.

From the Research

Definition and Characteristics of Clinically Isolated Syndrome (CIS)

• Clinically isolated syndrome (CIS) is a central nervous system demyelinating event isolated in time that is compatible with the possible future development of multiple sclerosis (MS) 4.
• CIS is a term that describes a first clinical episode with features suggestive of multiple sclerosis (MS), usually occurring in young adults and affecting optic nerves, the brainstem, or the spinal cord 5.
• The most common manifestations of CIS are long tracts dysfunction and unilateral optic neuritis, but it can also include isolated brainstem syndromes, cerebellar involvement, and polysymptomatic clinical image 6.

Diagnostic Criteria and Risk Factors

• Diagnostic criteria have been developed based on the clinical and MRI follow-up of large cohorts with CIS, providing guidance on how to utilize clinical activity in combination with radiographic information to diagnose MS 4.
• The 2010 McDonald criteria simplify requirements for dissemination in time and space and allow for diagnosis of MS from a baseline brain MRI if there are both silent gadolinium-enhancing lesions and nonenhancing lesions on the same imaging study 4.
• The risk of conversion to MS can be estimated based on many predictive factors, including epidemiological, ethnical, clinical, biochemical, radiological, immunogenetic, and other markers 6.
• Clinically silent MRI lesions and CSF oligoclonal bands are notable risk factors for MS, while weak or uncertain risk factors include vitamin D deficiency, Epstein-Barr virus infection, smoking, HLA genes, and miscellaneous immunological abnormalities 5.

Management and Treatment

• Early risk stratification for conversion to MS helps with treatment decisions, and magnetic resonance imaging (MRI) is currently the most useful tool to evaluate risk 4.
• Disease-modifying treatments delay the development from CIS to MS, and their use in CIS is limited by uncertain long-term clinical prognosis and treatment benefits and adverse effects 5.
• Interferons, glatiramer acetate, teriflunomide, cladribine, and some other agents have been evaluated in randomized, placebo-controlled, double-blind studies relying on large groups of patients with the first demyelinating event, and all of these drugs were shown to have beneficial effects in patients with CIS 6.
• Clinicians should select suitable CIS cases for steroid treatment to speed neurological recovery, and patients should be encouraged to adopt a healthy lifestyle, including smoking cessation 7.