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How Doctors Test for Multiple Sclerosis (MS)


Multiple Sclerosis (MS) is a demyelinating central nervous system ailment that is the most common cause of disablement of young adults. Although MS is far from rare, the diagnosis is not straight forward and is reliant on both clinical examination and advanced imaging techniques.

Clinical Suspicion of MS

As with most diseases and associated diagnoses, diagnosis of MS starts with clinical suspicion. Typical diagnostic clues are established in patients presenting with temporary visual or sensory loss, i.e., optic neuritis or transverse myelitis.

Patients may also have vague changes in reflexes, vision or ambulation that may provide further clues to establish clinical suspicion and elucidate the possibility of prior attacks.

Neurologic Examination

For patients suspected of having MS, a physician may decide to perform a fundoscopy, to view the optic disk as well as test color vision and any afferent pupillary defect with a flashlight test. Observation of eye movements can also help with diagnosis as internuclear ophthalmoplegia and Cranial Nerve VI palsy can be MS symptoms.

A gait analysis in this context can show foot dragging, as well as balance problems. On the other hand testing of tone and reflexes can help show upper motor neuron signs such as hyperreflexia which are relatively common in the context of MS.

Imaging

Magnetic resonance imaging (MRI) is the hallmark of MS diagnosis as well as ongoing management. It is the definitive test for MS. The latest recommendations call for both spinal cord and brain MRIs with and without contrast, unless there are particular contraindications such as allergies to contrast material. Diagnostic sensitivity of MRIs in the context of MS diagnosis are around 90% with specificities around 75%. Furthermore, MRI detects more MS plaques compared to CT and most of these lesions correlate with pathologies.

Brain MRI

Sagittal 3D fluid-attenuated inversion recovery (FLAIR) MRI is recommended as the initial tool for MS diagnosis due to high sensitivity. Although higher powered MRI scanners (e.g. 7T) can help distinguish nonspecific lesions from perivenular MS lesions, a 3T MRI is typically sufficient and a 1.5T MRI is acceptable.

Use of Gadolinium based contrast in the context of MS diagnosis helps exclude alternative diagnosis such as subarachnoid cysts as well as help elucidate active lesions from older non active ones.

Spinal Cord MRI

MRI of Spinal Cord is also suggested for all patients suspected of having MS. Although at least a 3T MRI scanner is preferred as in Brain MRI, there is no data to suggest that the use of a higher-powered MRI scanner leads to better diagnoses. Spinal cord MRI lesions are at least as common as brain MRI lesions and as there are less age associated artifacts on spinal cord MRI when compared with brain MRI, most lesions on spinal cord are non-silent.

Optical Coherence Tomography (OCT)

OCT utilizes infrared lights to visualize the retina and measure the retinal nerve fiber thickness. In most patients with optic neuritis, optic nerve demyelination leads to degeneration of the retinal nerve fiber layer. In this context, although OCT testing may definitively demonstrate retinal nerve fiber loss, the role of OCT in initial diagnosis of MS is not well defined.

Ancillary Testing

Blood Testing

Systemic diseases such as systemic lupus erythematosus, diabetes mellitus, thyroid diseases, infections such as Lyme or metabolic diseases such as Vitamin B12 deficiency can mimic MS or contribute to the severity of MS symptoms thus laboratory testing to exclude as appropriate are recommended.

Autoantibody Testing

In patients with high clinical suspicion of MS but atypical imaging findings, large spinal cord lesions or poor recovery from optic neuritis, physicians can test for autoantibodies in blood to evaluate for and distinguish neuromyelitis optica spectrum diseases. The most common antibodies that are tested are:

  • Aquaporin 4(AQP4) IgG. This antibody is a specific marker for Neuromyelitis Optica Spectrum Disorder (NMOSD). A disease that can present similar to MS, however typically with bilateral optic neuritis and complete spinal cord syndrome.
  • Myelin Oligodendrocyte Glycoprotein (MOG) IgG. This antibody is a marker for MOG antibody associated disease (MOGAD), while uncommon, can present with transverse myelitis and bilateral optic neuritis similar to MS as well as acute disseminated encephalomyelitis (ADEM).

Lumbar Puncture and Cerebrospinal Fluid Testing

Cerebrospinal fluid testing (CSF) used to be one of the standard battery of tests for initial MS diagnosis, however its use is exceedingly rare. CSF testing is currently reserved for patients with inconclusive MRI findings as well as to rule out infection. Qualitative measurement of oligoclonal IgG bands is the most important CSF test in the context of MS diagnosis. Oligoclonal bands are found in almost 90% of patients with MS, however, up to 10% of patients without MS will also have oligoclonal bands, thus the finding is not equivalent to diagnosis. Other CSF testing such as protein, albumin, cell count and glucose can also help with diagnosis though they are not specific nor sensitive.

Evoked Potentials

Evoked potentials are the electrical activity in the central nervous system when sensory organs are stimulated. Visual evoked potentials are helpful in patients with isolated spinal cord lesions to help establish diagnosis, especially if MRI is contraindicated due to a pacemaker or not tolerated due to claustrophobia. Around 70% of patients with MS will have abnormal visual evoked potentials, however, this test is not useful in monitoring the progression of disease. Finally, although auditory evoked potentials and somatosensory evoked potentials can also be used, they’re not as helpful in helping establish a diagnosis of MS.

Key takeaways

Although MS is the most common disabling disease of young adults, its diagnosis is far from straightforward.

The hallmark of diagnosis of MS is MRI scans. Ideally, both contrast and non-contrast Brain and Spinal Cord MRIs should be obtained in patients with suspicion of MS.

Blood work as well as ancillary testing such as CSF can also be utilized in the context of MS, however mainly to rule out diseases that may mimic MS or in cases where the diagnostic clues are high but MRI does not yield to diagnosis.

Resources:

Wattjes MP, Ciccarelli O, Reich DS, et al. 2021 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis. Lancet Neurol. 2021 Aug;20(8):653-670

Brownlee WJ, Swanton JK, Miszkiel KA, Miller DH, Ciccarelli O. Should the symptomatic region be included in dissemination in space in MRI criteria for MS? Neurology. 2016;87(7):680-683.

Newcombe J, Hawkins CP, Henderson CL, et al. Histopathology of multiple sclerosis lesions detected by magnetic resonance imaging in unfixed postmortem central nervous system tissue. Brain. 1991;114 ( Pt 2):1013-1023.

Poser CM, Paty DW, Scheinberg L, et al. New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol. 1983;13(3):227-231.

Bot JCJ, Barkhof F, Polman CH, et al. Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination. Neurology. 2004;62(2):226-233.

Petzold A, de Boer JF, Schippling S, et al. Optical coherence tomography in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol. 2010;9(9):921-932.

Sechi E, Shosha E, Williams JP, et al. Aquaporin-4 and MOG autoantibody discovery in idiopathic transverse myelitis epidemiology. Neurology. 2019 Jul 23;93(4):e414-20

Freedman MS, Thompson EJ, Deisenhammer F, et al. Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement. Arch Neurol. 2005;62(6):865-870.

Giesser BS. Diagnosis of multiple sclerosis. Neurol Clin 2011; 29:381

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