Multiple Sclerosis (MS)

A number of tests can be useful for the diagnosis, monitoring of disease progression, and evaluation of treatment effectiveness in patients with multiple sclerosis (MS). The main criteria for diagnosis of MS, according to the McDonald Criteria,1 include dissemination in space (DIS), dissemination in time (DIT), and ruling out other neuroinflammatory diseases that mimic MS symptoms.

The following tests can be useful for the diagnosis and monitoring of MS.

Physical and Neurological Examinations

Physical and neurological examinations can be useful first lines of observation in the diagnosis and monitoring of MS. Changes in heart rate, blood pressure, and body temperature can point to problems with homeostasis related to MS lesions and disease progression.2

Neurological assessments can also indicate possible central nervous system (CNS) lesions. Tremors or difficulty with coordination and gait can be indicative of cerebellar lesions. Changes in speech, facial sensations, or double vision may indicate brainstem damage. Transverse myelitis may be involved if changes in strength and sensation are observed, while optic neuritis could be involved if abnormalities in color vision, eye movements, or visual field or acuity are observed.2


After physical and neurological exams, imaging is the second most useful tool for the diagnosis and monitoring of MS. The results of the neurological exams can help identify locations to look for lesions. 

Magnetic resonance imaging (MRI) is one of the most useful imaging tools to investigate neurological lesions to diagnose MS through DIS and DIT as mentioned in the McDonald criteria.1 Specific MRI guidelines for MS diagnosis have been presented by the European research network Magnetic Resonance Imaging in MS (MAGNIMS).3 The use of T2-weighted fluid-attenuated inversion recovery (FLAIR) scans can help to observe overall disease burden through the size and location of lesions.2 The use of pre- and post-imaging with gadolinium contrast agent is useful for detecting lesions related to the breakdown of the blood-brain barrier (BBB).2 

Optical coherence tomography (OCT) of the retina can also be used to monitor white matter damage and neurodegeneration, especially in subclinical accumulation.4 OCT, especially spectral OCT (SOCT), has been found to be a useful tool for monitoring the thickness of the retinal nerve fiber layer and the total macular volume of the eye, which can be useful monitors of MS disease progression.5 

Lumbar Puncture

Cerebrospinal fluid (CSF) from lumbar puncture can be used for further testing in patients with MS, primarily for differential diagnosis from other CNS inflammatory disorders.6 CSF levels of glucose, overall protein, albumin, immunoglobulin G (IgG), and lactate are commonly investigated.6 Albumin and immunoglobulin levels in the CSF can be used to determine the permeability of the BBB. The existence of oligoclonal bands in the CSF can be used as additional evidence for the diagnosis of MS.7 The presence of oligoclonal bands in the CSF but not in blood serum can be even stronger evidence for MS diagnosis.8

Blood Tests

Several different biomarkers can potentially be useful for differential diagnosis as well as monitoring disease progression. A number of different microRNAs (miRNAs) have been found to be elevated or reduced in patients with MS. Research has shown a correlation between several miRNAs and MS symptoms including cognitive dysfunction and oxidative status that may lead to the depression and fatigue seen in many patients.9 Increased levels of miR-199a, miR-320, miR-155, miR-142-3p, and miR-142 have been found in peripheral blood mononuclear cells, while levels of miR-219, miR-34a, miR-103, miR-182-5p, miR-124, and miR-15a/b have been found to be reduced.9

A recent study found that elevated levels of plasma neurofilament light chain in early disease patients increased the risks of worsening disability.10 Another study suggested that certain metabolic biomarkers in the blood may be useful for differentiating relapsing-remitting MS (RRMS) from secondary progressive MS (SPMS).11

A number of other blood tests may be needed for differential diagnosis, such as renal and liver function, electrolyte levels, C-reactive protein, vitamin B12, thyroid hormone, lipid levels, viral antibodies, folate, vitamin D, venereal disease tests, and antinuclear, antiphospholipid, and anti-double-stranded DNA antibodies.6

Evoked Potentials

Prior to the use of MRI, evoked potentials were often used to detect lesions and as part of MS diagnosis.12 Now, a number of evoked potentials can be useful for monitoring the progression of MS as well as the effectiveness of treatment during clinical trials.13 Evoked potentials provide quantitative data to show disease progression and can be used to corroborate patient-reported symptoms.

Three main types of evoked potentials can be useful in MS patients, including motor, visual, and somatosensory.14 The changes to nerve conduction observed in evoked potentials, ranging from signal delays to blockages, can help to indicate the progression of demyelination.12

Functional Tests

Functional tests can also be helpful to show disease progression and have been used as outcome measures in clinical trials. Functional tests include the Kurtzke Expanded Disability Status Scale (EDSS),15 6-minute walk test (6MWT),16 timed 10-meter walk test (T10MW),17 9-hole peg test (9HPT),17 and the Multiple Sclerosis Functional Composite (MSFC) test.18

The EDSS is the most commonly used MS disability scale.19 It primarily focuses on ambulation and spans from values of 0 (indicating no disability) to 10 (indicating MS-related death). A number of other walking tests have been proposed over the years, including the 6MWT and T10MW. To focus more on upper limb disability, the 9HPT is used to monitor how long patients take to place and remove 9 pegs from 9 holes.20

For a more multifaceted functional assessment, the MSFC was developed. The MSFC monitors ambulation through a timed 25-foot walk, upper extremity function with the 9HPT, as well as auditory and cognitive function through the use of the Paced Auditory Serial Addition Test (PASAT).18


  1. Thompson AJ, Banwell BL, Barkhof F, et al. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018;17(2):162-173. doi:10.1016/S1474-4422(17)30470-2
  2. Wang C, Ruiz A, Mao-Draayer Y. Assessment and treatment strategies for a multiple sclerosis relapse. J Immunol Clin Res. 2018;5(1):1032.
  3. Filippi M, Rocca MA, Ciccarelli O, et al. MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol. 2016;15(3):292-303. doi:10.1016/S1474-4422(15)00393-2
  4. Costello F, Burton JM. Retinal imaging with optical coherence tomography: a biomarker in multiple sclerosis? Eye Brain. 2018;10:47-63. doi:10.2147/EB.S139417
  5. Kucharczuk J, Maciejek Z, Sikorski BL. Optical coherence tomography in diagnosis and monitoring multiple sclerosis. Neurol Neurochir Pol. 2018;52(2):140-149. doi:10.1016/j.pjnns.2017.10.009 
  6. Ömerhoca S, Akkaş SY, İçen NK. Multiple sclerosis: diagnosis and differential diagnosis. Noro Psikiyatr Ars. 2018;55(Suppl 1):S1-S9. doi:10.29399/npa.23418
  7. Cristiano E, Rojas JI, Alonso R, et al. Consensus recommendations on the management of multiple sclerosis patients in Argentina. J Neurol Sci. 2020;409:116609 doi:10.1016/j.jns.2019.116609
  8. Ziemssen T, Akgün K, Brück W. Molecular biomarkers in multiple sclerosis. J Neuroinflammation. 2019;16(1):272. doi:10.1186/s12974-019-1674-2

Reviewed by Harshi Dhingra, MD, on 7/1/2021.