What is the workup for Multiple Sclerosis (MS)?

From the Guidelines

The workup for multiple sclerosis (MS) involves a comprehensive approach combining clinical assessment, imaging, and laboratory tests, with MRI of the brain and spinal cord with and without contrast being the cornerstone of diagnosis, looking for characteristic demyelinating lesions disseminated in time and space, as recommended by the McDonald criteria 1. The initial evaluation should include a thorough neurological examination focusing on symptoms like vision changes, weakness, numbness, coordination problems, and bladder dysfunction. Some key points to consider in the workup include:

• Cerebrospinal fluid analysis to detect oligoclonal bands and elevated IgG index, which are present in about 85-95% of MS patients 1.
• Visual evoked potentials to help identify subclinical optic nerve involvement.
• Blood tests, including complete blood count, comprehensive metabolic panel, vitamin B12, folate, thyroid function tests, ESR, CRP, ANA, and other autoantibodies to rule out MS mimics.
• Additional testing, such as NMO-IgG/aquaporin-4 antibodies and anti-MOG antibodies, to distinguish MS from neuromyelitis optica and MOG-associated disorders 1. The McDonald criteria, which incorporate clinical and paraclinical evidence, should be applied to establish diagnosis, with the 2010 revision being the most recent and widely accepted criteria 1. Early diagnosis is crucial, as prompt initiation of disease-modifying therapies can significantly reduce relapse rates and slow disability progression, ultimately improving morbidity, mortality, and quality of life for patients with MS 1.

From the Research

MS Workup

• The diagnosis of multiple sclerosis (MS) requires a combination of clinical symptoms, magnetic resonance imaging (MRI) findings, and laboratory tests, including cerebrospinal fluid (CSF) analysis 2, 3, 4, 5, 6.
• CSF analysis is useful in supporting the diagnosis of MS, particularly in patients with clinically isolated syndrome (CIS) or radiologically isolated syndrome (RIS) 2, 3, 4, 6.
• The detection of oligoclonal IgG bands in CSF is a key diagnostic marker for MS, with a sensitivity of over 95% in patients with MS 2.
• The IgG index, which measures the ratio of CSF to serum IgG, is also elevated in approximately 70% of MS patients, but is not as sensitive as oligoclonal band detection 2.
• Other CSF biomarkers, such as free light chains, have emerged as potential diagnostic tools for MS, but require further validation 4.
• The 2017 McDonald Criteria are used to diagnose MS, and include a combination of clinical, MRI, and CSF findings 5.
• CSF analysis is also important in monitoring disease activity and response to treatment in MS patients 3, 6.

Diagnostic Criteria

• The diagnosis of MS requires the presence of at least two clinically distinct episodes of neurological symptoms, separated in time and space, and the presence of at least one lesion on MRI 5.
• CSF analysis is not mandatory for diagnosis, but is recommended in patients with negative MRI findings or in the absence of clinical symptoms 3, 6.
• The detection of oligoclonal IgG bands in CSF is a key diagnostic marker for MS, and is included in the MS diagnostic criteria 2, 3, 4, 6.

Laboratory Tests

• CSF analysis should include the determination of cell count and differential, protein and glucose, lactate, myelin basic protein, and the CSF/serum albumin ratio 6.
• Testing for oligoclonal IgG bands utilizing isoelectric focusing with IgG immunoblotting, the IgG synthesis rate, and the IgG index should be included in CSF analysis 2, 6.
• Other laboratory tests, such as MRI and evoked potentials, may also be useful in supporting the diagnosis of MS 5.