What is the recommended treatment approach for radiologically isolated syndrome (RIS) in multiple sclerosis (MS)?

Treatment Approach for Radiologically Isolated Syndrome in Multiple Sclerosis

For patients with radiologically isolated syndrome (RIS), regular MRI monitoring is recommended rather than immediate disease-modifying therapy, with follow-up brain MRI scans every 3-6 months after initial diagnosis to detect disease progression. 1

Definition and Monitoring Approach

• Radiologically isolated syndrome (RIS) refers to incidental MRI findings typical of multiple sclerosis in asymptomatic individuals without clinical evidence of demyelinating disease 2
• Regular brain MRI monitoring is essential for patients with RIS, with follow-up scans recommended 3-6 months after the initial MRI to detect new lesions 1
• The monitoring protocol should include T2-weighted, T2-FLAIR, and gadolinium-enhanced T1-weighted sequences to detect new or enlarging lesions 3
• Diffusion-weighted imaging should be included when monitoring for potential progression to clinically definite MS 3

Risk Assessment for Disease Progression

• Several MRI features are associated with higher risk of conversion to clinically definite MS:
  • Presence of spinal cord lesions 3, 4
  • Infratentorial lesions, particularly in the brainstem or cerebellum 3
  • Gadolinium-enhancing lesions on baseline or follow-up scans 5
  • Development of new T2 lesions on follow-up imaging 4
• CSF-restricted oligoclonal bands increase the risk of progression to symptomatic MS 4
• Younger age (≤37 years) has been associated with higher risk of conversion, though not consistently significant across all studies 5

Monitoring Frequency

• For standard RIS patients:
  • Brain MRI should be performed every 3-6 months in the first year after diagnosis 1
  • After the first year, annual MRI monitoring is recommended for patients with stable findings 1
• For high-risk RIS patients (those with spinal cord lesions, infratentorial lesions, or CSF oligoclonal bands):
  • More frequent monitoring (every 3-4 months) is recommended 1, 3
  • This allows for earlier detection of disease activity that might warrant treatment initiation 3

Treatment Considerations

• Current evidence does not strongly support immediate treatment of all RIS patients with disease-modifying therapies 2
• For high-risk RIS patients showing evidence of new lesion development on follow-up MRI:
  • Consider disease-modifying therapy, particularly if multiple risk factors for conversion are present 5
  • The decision to treat should be based on the presence of at least two risk factors for clinical conversion (spinal cord lesions, new T2 lesions on follow-up, gadolinium-enhancing lesions, or CSF oligoclonal bands) 4
• If treatment is initiated, dimethyl fumarate and glatiramer acetate have been commonly used in RIS patients 5

Pitfalls and Caveats

• Overtreatment risk: Initiating disease-modifying therapies in all RIS patients may expose many to unnecessary medication risks, as not all will convert to clinically definite MS 2
• Undertreatment risk: Delaying treatment in high-risk patients may miss the opportunity for early intervention during the optimal treatment window 5
• Diagnostic uncertainty: Ensure that RIS lesions truly represent demyelinating disease rather than mimics (vascular lesions, migraines, etc.) before establishing a monitoring or treatment plan 6
• Monitoring adherence: Emphasize the importance of consistent follow-up imaging, even in asymptomatic patients, to detect subclinical disease progression 1

Special Considerations

• The revised diagnostic criteria for RIS (2023) suggest that patients with fewer lesions than required in the 2009 RIS criteria may still be at significant risk for conversion to MS when additional risk factors are present 4
• Patients with RIS should undergo cognitive assessment using validated tools such as the Symbol Digit Modalities Test (SDMT) every 6 months, as cognitive changes may precede other clinical symptoms 7
• Consider ultra-high field MRI (7 Tesla) when available, as it may detect additional features like central vein sign, leptomeningeal enhancement, and cortical lesions that could further stratify risk 5