Do Multiple Sclerosis (MS) lesions typically appear on Magnetic Resonance Imaging (MRI) at the first onset of symptoms?

MS Lesions at First Onset of Symptoms

MS lesions are frequently present on MRI at the first onset of symptoms, but approximately 20% of patients with clinically isolated syndrome (CIS) who have normal brain MRI at baseline still convert to definite MS after 20 years.

Prevalence of MRI Lesions at Initial Presentation

• According to long-term follow-up studies, MS developed in 88% of patients with abnormal MRI results at presentation compared to only 19% of patients with normal MRI results 1.

• Brain MRI can be normal in some patients with MS despite clinical symptoms, particularly in those with:

  • Primary progressive MS (PPMS)
  • Symptoms primarily affecting the spinal cord
  • Early disease stage

• The 2019 Brain guidelines emphasize that MRI is formally included in the diagnostic work-up of patients with suspected MS, with focal white matter lesions being among the pathological hallmarks of the disease 2.

Spinal Cord Imaging Considerations

• Spinal cord imaging is crucial when brain MRI is normal or shows minimal abnormalities:

  • In a study of 20 patients with minimal or no brain MRI abnormalities, all had at least one visible spinal cord lesion 3.
  • Whole spinal cord MRI is recommended to meet dissemination in space (DIS) criteria 2.

• The presence of spinal cord lesions has significant prognostic implications:

  • Patients with spinal cord lesions detected early have a worse prognosis (4.4 times higher risk of reaching EDSS 4.0) 4.
  • Approximately 40% of spinal cord lesions are found in the thoracolumbar region, supporting the need for imaging the entire cord 2.

Presymptomatic Phase and Normal-Appearing Tissue

• MRI can detect abnormalities before clinical symptoms develop:

  • A longitudinal study documented a patient with significant MRI disease activity during a presymptomatic phase 5.
  • The patient developed 43 new lesions before experiencing clinical symptoms, with only one lesion located in a neurologically eloquent area.

• Subtle changes outside visible T2 lesions (normal-appearing brain tissue) can be detected with advanced imaging techniques:

  • Patients with these changes have a higher risk of developing clinically definite MS 6.
  • The American Academy of Neurology notes that advanced MRI techniques may reveal abnormalities in normal-appearing white matter when conventional MRI appears normal 7.

Clinical Implications and Diagnostic Approach

• A normal brain MRI cannot definitively exclude MS, as approximately 20% of CIS patients with normal baseline MRI still convert to MS after 20 years 7.

• When clinical suspicion remains high despite normal initial MRI:

  • Consider spinal cord imaging
  • Consider cerebrospinal fluid analysis for oligoclonal bands
  • Repeat brain MRI in 3-6 months
  • Consider advanced MRI techniques

Pitfalls and Caveats

• The McDonald criteria should only be applied in the appropriate clinical context when onset is characterized by typical MS manifestations 2.

• Misdiagnosis risk increases when:

  • Few lesions are present
  • Patient has comorbidities (e.g., migraine or cerebrovascular disease)
  • Clinical presentation is not typical of MS

• Current MRI criteria for MS are based on imaging features that are characteristic of the disease but not sufficiently specific, requiring careful interpretation by experienced readers 2, 7.

• A normal MRI should prompt thorough investigation for alternative diagnoses, as emphasized by multiple guidelines 2, 7.