Multiple Sclerosis Centers of Excellence

Diagnosing Multiple Sclerosis Using the McDonald Criteria

Rebecca Spain, MD, MSPH -- Portland, OR
Lindsey Wooliscroft, MD -- Portland, OR

The basis of MS diagnosis is by determination of "lesions disseminated in space and time”. In other words, MS plaques occurring in multiple parts of the central nervous system (CNS) and over the course of time. The diagnosis is by clinical criteria with support as necessary from MRI and spinal fluid analysis. The criteria have evolved over time to allow more rapid diagnosis of MS and thus permit earlier treatment of MS. The diagnosis of MS can be challenging, and is focused on excluding MS mimics that have alternative treatments. Given that MS is a clinical diagnosis that can evolve over time, careful follow-up of patients is necessary to confirm that MS, once diagnosed, remains the best possible diagnosis.

Diagnostic Criteria

Diagnostic criteria have evolved over time from the Schumacher Criteria (1965), to Poser Criteria (1983), and finally to the McDonald Criteria (2001). The McDonald Criteria were developed by an international panel in association with the National MS Society of America, modified in 2005, and revised again in 2010 and 2017. The McDonald Criteria revisions enable more rapid diagnosis of MS and thus permit earlier treatment of MS. For clinical research trials, the McDonald Criteria ensure that those without a definite diagnosis of MS are not enrolled. 2017 McDonald Criteria

Diagnosing MS

The clinical diagnosis of MS is made after thorough evaluation, usually by a neurologist or another provider with experience working with MS, and is not based on one specific physical finding, laboratory test, or symptom. Importantly, the diagnosis of MS relies on exclusion of other causes of symptoms and signs that might otherwise suggest MS, but are accompanied by “red flags” that point to an alternative and unifying diagnosis (Toledano 2015). In addition, it’s important to understand what imaging findings are and are not typical of MS to avoid misattributing MRI lesions to MS. The diagnosis of MS takes time and can be challenging.

The symptoms of MS can come and go, and they are not the same for every person. Since the diagnosis of MS is a clinical diagnosis, MRI and laboratory testing are not required. However, given the high sensitivity and specificity of MRI findings in MS, and the utility for monitoring disease and response to therapy, MRI is nearly universally conducted when possible.

An MRI has the ability to show dissemination in space with lesions in typical locations, and dissemination in time with the presence of simultaneous enhancing and non-enhancing lesions, or new lesion formation on a subsequent MRI. Consensus recommendations are to use brain MRI with and without contrast for initial diagnosis (Filippi 2016). Spinal cord imaging is indicated if the clinical exam localizes to the spinal cord, or the brain MRI does not demonstrate dissemination in space. The whole cord (cervical through lumbar) spinal cord imaging is advised with and without contrast, however the bulk of the cord lesions occur in the cervical and thoracic cord.

Additional testing for the diagnosis of MS may be necessary, including blood tests and spinal fluid analysis. Elevated CSF oligoclonal bands, an elevated IgG index, and/or IgG synthetic rate is found in about 75% of people with MS. In patients with one clinical attack and evidence on two or more typical lesions on MRI, the presence of oligoclonal bands can establish dissemination in time (and thus a diagnosis of MS) with the 2017 McDonald Criteria. There is no one laboratory, MRI, or clinical test that definitively rules in or rules out MS.

Relapsing MS

85% of people with MS have a relapsing form of MS at onset. Relapsing MS diagnosis requires objective clinical evidence of two or more CNS lesions (dissemination in space) that have occurred at different times (dissemination in time), or objective clinical evidence of one lesion with reasonable historical evidence of a prior attack. The reasonable historical evidence can be documentation by a prior provider of symptoms and signs attributable to an acute CNS attack. A good patient historian can also give a description of symptoms that are typical for MS and thus can be the historical event. Descriptions of fully or partially reversible symptoms that describe optic neuritis, transverse myelitis, a brainstem syndrome, or other symptoms clearly referable to the CNS represent good historical evidence of a prior attack. Symptoms such as headache, poor cognition, fatigue, and generalized weakness, although they could be due to MS, are not specific for MS or even a CNS event and should not count as a historical attack. An MS attack should last at least 24 hours, usually lasts no more than 1-2 months, and resolves fully or partly with residual symptoms. Dissemination of attacks in space and time is the cornerstone of MS diagnosis.

Primary Progressive MS

15% of people with MS have a progressive form at disease at onset, defined as a gradual worsening of neurological symptoms and signs referable to the CNS for at least 1 year. Diagnosis of primary progressive MS can be more challenging and relies more heavily on ruling out other causes of symptoms. The MRI and spinal fluid evaluation is used more often in primary progressive MS to support the diagnosis. The 2017 McDonald Criteria also cover the requirements to diagnose primary progressive MS. It is important to distinguish relapsing from primary progressive MS as the treatments can be different.

Secondary Progressive MS

After approximately 15-20 years, about half of the people initially diagnosed with relapsing MS transition to secondary progressive MS. In this phase, there is gradual worsening of neurological symptoms and signs between MS attacks. In many, MS attacks eventually stop altogether, but some have both relapses and progression. It is important to recognize if a relapsing patient also has a progressive component between attacks to their disease as current MS therapies do not effectively slow the progressive aspect of MS. Secondary progressive MS does not have set criteria and is not part of any MS diagnostic criteria.

Clinically Isolated Syndrome

Clinically Isolated Syndrome (CIS) is a term that describes an isolated episode of neurological symptoms caused by inflammatory disease of the brain or spinal cord that do not meet 2017 McDonald criteria for MS (Brownlee 2014). CIS can be monofocal, meaning a single symptom such as vision loss from optic neuritis, or multifocal due to lesions in several locations.

In diagnosing CIS, the physician faces two challenges: first, to determine whether the person’s symptoms are cause by CNS inflammation and not another process, and second, to determine the likelihood that a person experiencing this type of demyelinating event is going to develop MS. A person with CIS has a higher risk (70-80%) of developing MS when the CIS is accompanied by MRI-detected brain lesions that are similar to those seen in MS (i.e. typical lesions). Conversely, there is a lower risk (20-30%) for MS when the MRI does not show brain lesions. A radiologist or neurologist trained in examining lesions is helpful in determining if lesions, if present, are typical of MS.

An accurate diagnosis of high or low-risk CIS is important because people with a high-risk CIS are encouraged to begin treatment with a disease-modifying medication to delay or prevent a second neurologic episode and, therefore, the onset of MS. In addition, early treatment may minimize future disability caused by MS. Several medications are now approved by the FDA for CIS.

Abnormal Brain MRI

Occasionally, people get brain MRIs for reasons other than suspected MS such as a car accident or migraines. Sometimes these MRIs look similar to ones from people with MS. MRI mimics of MS are numerous, and not all radiologists are familiar with current MRI criteria (Aliaga 2014). It is important to remember that the radiologist cannot make the diagnosis of MS as it is a clinical diagnosis based on history and neurological examination. Patients with abnormal MRIs that are suspicious for MS should be evaluated for a history of events typical of MS or neurological findings referable to the CNS. Usually a neurologist is best able to perform this evaluation.

In VA, the vast majority of Veterans have already been diagnosed – often in the military or in the private sector. Patients diagnosed prior to MRIs or by another provider deserve to have the original and ongoing basis for their diagnosis reviewed in light of the 2017 McDonald Criteria. This is important as MS treatment comes with risks to the patient, which can be avoided with correct diagnosis.

Summary Points

• MS is a clinical diagnosis based on lesions disseminated in space and time.
• There is no single test for MS, and MS mimics must be excluded.
• MS diagnosis cannot be made with MRI alone.
• The best and most current diagnostic criteria are the 2017 McDonald criteria.
• The goal is to diagnosis MS as soon as possible after an initial neurological attack and initiate MS therapy.
• High-risk CIS patients should be offered MS therapies approved for CIS.
• Best evidence is that early MS therapy delays onset of MS for CIS patients, reduces MS clinical attacks, and reduces long-term disability in MS.

Additional Information

• Aliaga ES, et al. MRI Mimics of MS. Handb Clin Neurol. 2014:122:291-316.
• Filippi M, et al. MRI Criteria for the Diagnosis of MS: MAGNIMS Consensus Guidelines. Lancet Neurol. 2016 Mar;15(3):292-303.
• Gaetani L, et al. 2017 Revisions of McDonald Criteria Shorten the Time to Diagnosis of MS in Clinically Isolated syndromes. J Neurol. 2018 Sep 8.
• Odenthal C, et al. The Prognostic Utility of MRI in Clinically Isolated Syndrome: A Literature Review. AJNR Am J Neuroradiol. 2015 Mar:36(3):425-31.
• Polman CH, et al. Diagnostic Criteria for MS: 2010 Revisions to the McDonald Criteria. Ann Neurol. 2011 Feb;69(2):292-302.
• Solomon AJ, et al. Undiagnosing MS: The Challenges of Misdiagnosis of MS. Neurology. 2012 Jun 12:78(24):1986-91.
• Thompson AJ, et al. Diagnosis of MS: 2017 Revisions of McDonald Criteria. Lancet Neurol. 2018 Feb:17(2):162-173.
• Toledano M, et al. A Clinical Approach to the Differential Diagnosis of MS. Curr Neurol Neurosci Rep. 2015 Aug;15(8):57.

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