Can multiple sclerosis (MS) occur without demyelinating lesions?

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From the Guidelines

Multiple sclerosis (MS) cannot be definitively diagnosed without lesions, as the presence of lesions is a cornerstone for MS diagnosis, and at least one clinical event consistent with acute demyelination remains necessary for a firm diagnosis. According to the 2016 Magnims consensus guidelines published in The Lancet Neurology 1, a diagnosis of MS based solely on incidental findings on MRI, even with additional supportive findings, is problematic. The guidelines propose that identical criteria used for MS should be applied for the evaluation of radiologically isolated syndromes (RIS), and a diagnosis of MS can be made when a clinical attack occurs in RIS subjects with disseminated lesions in time (DIT).

Some key points to consider in the diagnosis of MS include:

  • The presence of oligoclonal bands (OBs) in cerebrospinal fluid, which may indicate a higher risk of developing MS 1
  • The use of advanced MRI techniques, such as higher-field strength MRI or specialized sequences, which may detect lesions not visible on conventional MRI 1
  • The importance of monitoring patients over time with repeat MRIs, as lesions often develop later 1
  • The need for additional tests, such as evoked potentials or optical coherence tomography, to detect subtle nervous system damage in patients with suspected MS and normal imaging 1

It is essential to note that while some patients may have symptoms consistent with MS without visible lesions, a firm diagnosis of MS requires the presence of lesions and at least one clinical event consistent with acute demyelination, as stated in the 2016 Magnims consensus guidelines 1.

From the Research

Multiple Sclerosis without Lesions

  • Multiple sclerosis (MS) is a chronic and often disabling autoimmune disease that affects the central nervous system, characterized by the presence of white matter lesions in the brain and spinal cord 2.
  • However, a minority of patients with MS may have normal brain MRI, with minimal or no abnormalities, despite presenting with symptoms and signs referable to the spinal cord or optic nerves 2.
  • In such cases, imaging of the spinal cord can be of considerable value in supporting the diagnosis of MS, as all patients with normal brain MRI but abnormal spinal MRI had at least one lesion visible in the spinal cord 2.

Diagnostic Criteria and Biomarkers

  • The presence of oligoclonal bands (OCBs) in the cerebrospinal fluid (CSF) is a powerful evidence for the diagnosis of MS, with more than 95% of patients with MS having CSF OCB of IgG class not detectable in serum 3.
  • The IgG index, which is elevated in about 70% of MS patients, can provide additional evidence for an augmented B-cell response within the CNS, but its diagnostic sensitivity is lower than that of CSF OCB 3.
  • The presence of CSF-specific OCB has been identified as a highly predictive factor for the conversion to definite MS in patients with isolated transverse myelitis, emphasizing the significance of conducting timely CSF analysis in such patients 4.

Pathogenesis and Disease Progression

  • Neurodegeneration is increasingly being recognized as an important factor in the pathogenesis of MS, and MRI measures of brain atrophy have been suggested as surrogate markers of neuroaxonal loss and disease progression 5.
  • The precise antigenic specificity of OCBs remains elusive, but evidence suggests that they are under genetic control and originate from clonal B-cells in both the periphery and CNS, with a potential role in demyelination and axonal injuries 6.

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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