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Multiple Sclerosis Diagnostic Criteria

Common Clinically Isolated Syndromes – Diagnostic Criteria for Relapsing Remitting and Progressive Forms of Multiple Sclerosis – Radiologically Isolated Syndrome

Diagnosis of Multiple Sclerosis


The diagnosis of multiple sclerosis is based on the combination of symptoms, findings on neurological examination, symptoms evolution over time, and findings on the diagnostic tests. MS diagnosis criteria have always been evolving but some essential criteria have been staying for years.

This is a “dissemination of symptoms in space and time”. This statement implies that the symptoms have to recur (dissemination in time) and that MS lesions have to be localized in multiple areas of the brain and/or spinal cord (dissemination in space).

There are two major types of MS: relapsing-remitting and progressive. The former is characterized by recurrent neurological problems (relapses) separated by periods of time with no apparent disease progression (remissions). Neurological problems acquired during relapses either partially or completely resolve during remissions.

In primary progressive MS, neurological symptoms gradually develop over time without evidence of improvement. Relapsing-remitting form may turn into progressive MS years down the road.

As any disease, MS starts with some symptoms. The very first attack of multiple sclerosis is called a clinically isolated syndrome. Clinically isolated syndrome may be a single such event over a life time. More often, however, it will convert to multiple sclerosis over years

Even though the syndromes described below are classical for MS, a single such event is not sufficient for the diagnosis of multiple sclerosis. MS diagnostic criteria will be discussed later.

Common Clinically Isolated Syndromes in MS

Optic Neuritis in MS

Optic neuritis typically starts with pain in the eye followed by loss of vision. Pain lasts for a few days. Loss of vision may start immediately or may be delayed. The degree of vision loss is variable from blurred vision to profound loss of vision. Gradual recovery starts within weeks. Please see optic neuritis article for more details.
Optic neuritis may be an isolated disease or it may be caused by other than MS disorders. Normal brain MRI is associated with only 25% of MS over 15 years. Presence of MS specific brain lesions makes it 72% chance of conversion to MS over the same period of time.

Brainstem and Cerebellum Symptoms in MS

Involvement of these brain areas is classical for MS. The most typical symptoms are  internuclear ophthalmoplegia; sixth nerve palsy (inability to turn the eye outwards); ataxia (lack of coordination) with nystagmus (jerky eye movements); numbness in the face; vertigo; hearing loss.
Similar to optic neuritis, lack of specific demyelinating lesions on the MRI carries only 20% chance of conversion to MS. Presence of specific lesions on the MRI carries 60% to 90% chance of MS in the future.

Transverse Myelitis in MS

Myelitis (inflammation in the spinal cord) is not unique for MS. Please see transverse myelitis page for more details. Here are some features of myelitis that are rather specific for multiple sclerosis – symptoms develop over hours to days; lack of drastic weakness in the legs or lack of any weakness; numbness and tingling in the body below the neck as a single symptom; Lhermite Sign; lack of arm position sense; improvement without any treatment.

There is only 20% chance of MS if the Brain and Spine MRIs reveal no specific lesions. Presence of demyelinating plaques is associated with 60% to 90% chance of multiple sclerosis.

Radiologically Isolated Syndrome in MS

This name refers to presence of MS suspicious lesions on the brain and/or the spinal cord MRIs without any prior or recent history consistent with multiple sclerosis.

Once the criteria for the number and the location of MS-specific lesions are met, there is a substantial risk of MS (30% to 59.

Specific criteria for the diagnosis of Radiologically Isolated Syndrome in MS are under development at this point.

Diagnosis of Relapsing-Remitting Multiple Sclerosis

Considering rapidly evolving treatment options for MS, the necessity for the early diagnosis is becoming more important. The official diagnostic criteria are constantly changing. Below are findings specific for relapsing remitting multiple sclerosis. The following is based on MS McDonald Criteria 2010.

Multiple sclerosis starts as relapsing-remitting form in 80% to 85% of cases. First symptoms typically appear between ages 20 and 40. Ninety percent develop first MS symptoms between 15 and 50 years. Less than 1% has disease onset before age 10 or after age 60.  MS is much more common in females.

One or multiple symptoms described in MS Symptoms article come first. Neurological problems last from days to weeks. The symptoms gradually resolve, either partially or completely. It is not MS yet because the criterion for the dissemination in time has not been met yet. In order to make the diagnosis of MS, some evidence about prior attacks has to be collected.

Let’s say, there were no prior events suspicious for multiple sclerosis. At this point, there is only 20%-25% chance of MS in the future. It is called a clinically isolated syndrome.

The next step is an MRI of the brain and the spinal cord. Lack of MS specific lesions on the MRI has the best long term prognosis regarding MS. Presence of the brain or the spinal cord specific lesions on the MRI makes prognosis less favorable, or 60% to 90% chance of developing MS.

Nevertheless, the idea of dissemination in space and time still applies. If the MRI shows a specific recent (contrast enhanced) demyelinating plaque on MRI, which perfectly explain the symptoms, then it is not officially MS yet; even though there is a high probability of MS in the future. Many MS experts perceive that these patients have to be treated anyway.

Now it becomes a “wait and see” approach. It is reasonable to repeat brain and spine MRI in a few months. Presence of new demyelinating plaques on the subsequent MRIs is diagnostic of multiple sclerosis, even if there are no new symptoms.

The same holds true for subsequent relapses. Any future neurological symptoms, irrelevantly of MRI findings, are diagnostic of MS. In both cases the criteria of dissemination in time and space are met.
Presence of MS specific old lesions on the MRI at initial presentation is diagnostic of MS as well.

Subsequent disease progression is judged based on the presence of new lesions on the MRI, new relapses, and the level of accumulated disability.

What are MS Specific MRI Findings?

The  location and the shape if the lesions are very important. Typical MS demyelinating plaques are oval periventricular (corpus callosum), juxtacortical, in the brain stem/cerebellum (infratentorial), or in the spinal cord.
Spinal cord lesions do not involve the whole thickness of the cord, located on the periphery, and span no more than 2 segments of the spinal cord. Extensive involvement of the spinal cord is more typical for neuromyelitis optica or other diseases.

Presence of at least one plaque in two of these locations (total 2) is considered specific for MS. I realize that you don’t understand these terms but this is how it is written in the MRI reports.

Spinal Tap is not essential for relapsing-remitting MS diagnosis any longer. It is reserved for cases, when some other cause is suspected. Presence of oligoclonal bands and elevated IgG index are specific for MS.

Diagnosis of Primary Progressive Multiple Sclerosis

Primary progressive MS is less common than relapsing-remitting. It affects 10% to 15% of the patients. Unlike relapsing-remitting form, it is equally distributed between genders. Mean age of onset is 40 years (30 years for relapsing-remitting). Most common presentation is gradual development of difficulty walking, legs weakness, imbalance, spasticity (increased muscle tone, stiffness) and incontinence. Sensation abnormalities are less likely. Mild intermittent improvements in neurological symptoms are possible.

Unlike relapsing-remitting MS, in progressive MS degenerative mechanisms play the major role. Demyelinating changes in the brain cortex are more prominent in progressive form of MS, so do brain atrophy and axonal loss (loss of nerve cell processes rather than myelin alone). Several mechanisms of primary MS have been proposed but they are all hypothetical.

Primary progressive MS is caused mostly by spinal cord and less commonly by brain stem involvement. MRI reveals demyelinating plaques predominantly in the spinal cord. These plaques don’t tend to enhance (light up) with contrast. The plaques are fainter and are fewer in numbers.

McDonald Criteria for diagnosis of primary progressive MS are as follows:
At least one year of neurological symptoms progression combined with at least 2 of the following:
– At least one of MS specific brain lesions in periventricular, juxtacortical, or brain stem/cerebellum areas
– At least 2 MS lesions in the spinal cord
– Positive cerebrospinal fluid for oligoclonal bands and/or elevated IgG index

Secondary progressive MS

Secondary progressive MS develops in about 25% to 40% of patients with relapsing-remitting form. Secondary progressive pattern tends to develop later in the disease (in about 20 years after diagnosis of MS).

Secondary progressive MS is characterized by gradual deterioration of gait, balance, spasticity, and incontinence irrelevantly of apparent relapses over at least half a year. Relapsing features may still persist.

Typical presentation, specific MRI and CSF (cerebrospinal fluid) findings are usually sufficient for the diagnosis.

Deviation from those require search for other causes, which are numerous.
Alternative diagnoses are beyond the scope of this article.


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