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Diagnosing MS - The McDonald Criteria (revised 2005)
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(The Myth of the 9 Lesions)

Approach to the Diagnosis of Multiple Sclerosis

First, you need to understand that MS always was, AND STILL IS, mainly  a clinical diagnosis.   The definition of “Clinical Diagnosis” is:
A diagnosis that can be made on the basis of the history and the physical exam alone.

Yes, that means that in some cases, the diagnosis of MS can be made without using the MRI or other test at all.  However, this is unusual, but it points out clearly the need for a thorough history and physical at the beginning of the diagnostic process.  Many of the clues to the disease will already  be there.  In countries where MRIs are available, they are always obtained.  And, in practice, the results of the MRI often overshadow the "clinical" findings from the patient's history and the neurological exam, especially if the MRI is negative or atypical.  According the guidelines of diagnosis, this MRI would not have to be positive in order for the neurologist to be confident the person has MS.  However, it takes a smart and very confident neurologist, usually an MS Specialist, to diagnose MS with a normal MRI.  It does happen, though.

The categories of MS are also based solely on the patient's experience, that is, their history of symptoms, of resolution, and of accumulation of disability.  The categories are discussed more fully in another Health Page (see "Categories of MS").  These are Relapsing Remitting MS (RRMS), Secondary Progressive MS (SPMS), Primary Progressive MS (PPMS), and Progressive Relapsing MS (PRMS).  About 85% of people with MS will have the Relapsing Remitting form.  For this reason, physicians begin looking a patient with suspected MS from the standpoint of attacks and remissions.
What is an Attack?

An attack (relapse, flair, exacerbation) of MS is the appearance of new neurological symptoms or the worsening of old neurological symptoms of the kind that are seen in MS.  An attack may be documented from the report of the patient.  In this case it is subjective.  Or it may be observed by the doctor (as in descovering a new problem on the neuro exam), though usually it is a combination of the two.  Anything problem observed by the doctor is said to be "objective."  An attack must last at least 24 hours. 

An attack does not include a pseudoattack, which is the temporary worsening of symptoms that can occur elevation of the body's core temperature (as with fever or overheating).  It also does not include single paroxysmal events (sudden jerks, brief loss of vision, single spasms of a muscle, a single bout of dizziness).  If the single event occurs mutliple times over a period of more than 24 hours it would qualify as an attack.  As noted above an attack often does include more than one symptom.

Note:  The definition of "attack" used in the McDonald Criteria is more strict than the definition used to discuss MS in general.  The difference is the requirement that each attack have an objective finding on physical exam.  The report of a sensory abnormality, like a paresthesia, is not enough.

How Often Can Attacks Occur?

The time between attacks must be at least 30 days, during which the symptoms improve, resolve, or are stable in their intensity.  So, a second attack must be at least 30 days from the day the first attack began to improve or stabilized.  This period between attacks is called a remission.  Clinically, a patient with RRMS is always either in an attack or in a remission.

The Importance of the History and Physical

So you can see that the whole diagnostic process must begin with a thorough history from the patient of their symptoms, when they started, how they progressed, whether they improved and how much they improved, and whether they ever returned.  It must look for a pattern of waxing and waning of symptoms, noting when new symptoms appeared.  The physician must put together a timeline of the patient's complaints and symptoms looking for a pattern of "Relapse and Remission."   The history should include the things that make symptoms worse or improve them, the pattern of symptoms severity with respect to time of day, level of exercise, temperature, and whether the symptoms became worse after things like infections, pregnancy, severe life stressors, or overexertion.  It should be complete in other respects including non-neurological symptoms and events especially just preceding any attacks.

The patient's Family History should be noted with respect to neurological illnesses, including MS, and for signs of MS Mimics in other members of the family, especially cases of autoimmune disease.  It is imperative that the neurologist pay close attention and devote time to hearing what the patient can offer.  No patient should be comfortable with a doctor that does not take this time in one way or another.

The neurological exam is just as important!  It should be a thorough exam, that takes a good amount of time, often upwards of an hour.  It should cover multiples tests in each part of the neurological system.  It is a head to toe exam, and done well, can be exhausting.  It should cover the multitude of tests of the face muscles and eye movements.  There is also a thorough check of the major muscle groups through the body comparing one side to the other for symmetry.  There should be checks for balance and coordination.  There should be some testing of the sensation throughout the body using 2 or more tests of sharp/dull, soft touch, hot/cold, vibration, two-point discrimination and joint point-position sense.  The doctor should observe the patient walking a good distance (more than the 4 steps across the exam room), walking on the toes and on the heels.  Finally, several tendon reflexes should be checked and compared side to side.

During the neurological exam the doctor is looking for "clinical lesions."   A clinical lesion is an abnormality on the exam that is objective evidence that there is damage in the nervous system.   Examples of "clinical lesions" are 1) hyperactive reflexes which show that there is damage in the spinal cord, 2) problems with the muscles that move the eyes indicating a problem in the brainstem, 3)  spasticity, usually also from the spinal cord,  4) positive Babinksi or Hoffman's test, and 7) paleness of the optic disc at the back of the eye.  These are just a few of many dozens that can occur.

Please note that the word lesion is used in two different ways throught discussions of MS.  There are "clinical lesions" as described above.  These are abnormalities on the exam that must indicate areas of damage in the central nervous system.  There are also "MRI  lesions" which are the abnormalities seen on the MRI images.  The two are not always the same.  One can have a clinical lesion that does not show up on the MRI.  There can also be white spots on the MRI that don't appear to have a symptom associated with them.  For clarification of this point please see the Health Page "Lesions vs. Symptoms."

So, it becomes clear that the neurologist must listen to and exam the patient carefully at some point early in the diagnostic process before making any judgment on the diagnosis.  The first clues about whether this is MS, a mimic or something else will come from this process.  Be wary of the neurologist who skips these steps.

What is the Neurologist Looking For?

The actual terms used by MS Specialists in describing the diagnostic characteristics of MS are Dissemination in Space, Dissemination in Time, and the Exlcusion of Any Better Explanation for the patient's symptoms and findings.

Dissemination in Space - This means that there is evidence that the disease has attacked more than one area of the Central Nervous System.  The disease has "spread out in location."

Dissemination in Time - This means that there have been attacks on the Central Nervous System on more than one occasion.  The disease has "spread out in time."   It has been active more than once.  The attacks must have occurred at least 30 days apart.

Exclusion of Better Explanations - To do this the neurologist will order many blood tests looking for MS mimics, such as causes of autoimmune vasculitis such as Lupus or Sjogren's Syndrome, CNS infections like Lyme Disease and syphillis, blood clotting disorders like Hughes Syndrome, vitamin deficiencies, and heavy metal poisoning.  Also other tests may be done like an EEG often looking for a type of seizure called "partial comples seizures," sleep study looking for sleep apnea, and  EMG + Nerve Conduction Studies, looking for damage to the nerves outside the CNS called "peripheral neuropathy."


In 2001, a new set of diagnostic criteria were proposed and accepted by the MS world of doctors and researchers. The McDonald criteria were  very good, in that, for the first time they described criteria for the diagnosis of Primary Progressive MS, but they also allowed for the definitive diagnosis of MS in it’s earliest form (often called the Clinically Isolated Syndrome, when there had been only one “attack” or onset of one symptom.)  The diagnosis of these two situations requires real thought and documented abnormalities on the lab and imaging tests.   These criteria were superior to ealier diagnostic guides in that they were better at picking the MS cases accurately and eliminating the non-MS cases. 

For the first time, neurologists could use the information from MRIs to substitute for an attack or for more evidence of clinical lesions when the clinical history was not enough to show a pattern of the spread of the disease in time and space.  This allowed many people to be diagnosed earlier.  In the last 10 years, MRI has become more and more important in the diagnosis of MS.  The problem is that some neurologists have come to rely solely on the MRI results and may neglect the patient's history and physical almost completely.  As you examine the McDonald Criteria, you will see that the Criteria never intended that the MRI assume the first and only role.

By theMcDonald Criteria, patients fall into one of three categories: Definite MS, Possible MS and Not MS.  The “type of MS” (RRMS, SPMS, etc) is determined after diagnosis and is based almost entirely on the patient's clinical course.

There were problems, though, in the practical use of the McDonald Criteria.  The MRI criteria were very stringent and difficult to figure out.  Also, new techniques in MRI imaging made visualizing spinal lesions easier.  It was clear that spinal lesions needed a larger role in the diagnosis.

The Revised McDonald Criteria (2005)

In 2005, a group of MS specialists reconsidered the original criteria, loosened some of the MRI requirements, changed the role of the results of CSF testing and VEP in the diagnosis of PPMS, and increased the importance of spinal MRI lesions.  These changes have been shown to be as good or better at picking up patients with MS and in excluding patients who do not have it. 

Below is a chart summarizing the revised criteria.  After the chart is a text description in more detail about the different cases a neurologist finds.


What Provides MRI Evidence of Dissemination in Space?

This is the description of a postivie MRI for the purposes of showing that there has been "dissemination in space."  This would be needed if there is only evidence on neurologic exam of one clinical lesion.  There is only one abnormality that points directly to a damaged area in the CNS.  This is also where the misunderstanding about always needing 9 lesions on the MRI.  (Sometimes you do, but not always.)  In general lesions should be larger than 3mm in cross-section.
    You need to have 3 of the following 4 things:

  • 1 (one) contrast-enhancing lesion of the brain or spinal cord.  If no enhancing lesion, then need 9 T2 hyperintense lesions in brain or spine.
  • 1 infratentorial lesion or a cord lesion (this means under the tentorium, which is the membrane on which the larger cerebrum sits.  Below the tentorium is the cerebellum, brainstem and spinal cord.)
  • 1 (one) or more juxtacortical lesions (this involves nerve fibers - called U-fibers - that extend from the white matter in the subcortical area through the boundary with the cortex of the gray matter)
  • 3 or more periventricular lesions (these are lesions sitting adjacent or very close to the ventricles)

important note:  Individual cord lesions can substitute along with individual brain lesions to reach the required number of T2 lesions.

What Provides MRI Evidence of Dissemination in Time?

  • A Contrast-Enhancing (therefore new) MRI lesion seen in a scan done at least 3 months after the onset of the first attack and at a site that is different from the site of the inital clinical attack.  (an example would be: first attack was with Optic Neuritis.  3 months later there is an enhancing lesion in the frontal lobe)


  • A new T2 lesion detected in a scan done at any time compared to an earlier scan.  The earlier scan must have been done at least 30 days after the beginnig of the first clinical attack.

What is a Positive CSF (Spinal fluid) Result?

Two or more unique oligoclonal bands found in the CSF, but not in the serum OR an elevated IgG Index

What is a Positive VEP?

A delayed optic nerve signal (usually longer than 115msec), but a well-preserved wave form

What Does the Chart Say in Real Words?

The neurologist is usually faced with one of several situations.  Each one begins with an analysis of the patients history of symptoms looking for a pattern of attacks and a thorough neurologic exam to look for clinical lesions.  Ideally the patient would have seen a physician for each of these attack, but this often is not the case.  Then the picture becomes much murkier.  Each scenario below assumes that all other reasonable expalnations for the patient's problems has been ruled out.  They are listed by ease of making the diagnosis.

First scenario
2 attacks
2 clinical lesions

The patient has had 2 or more attacks by history, with a clearcut remission between at least two of them.  A doctor has found neurologic abnormalities during at least 2 attacks.  There are or have been at least two objective clinical lesions in separate parts of the body.  In order to make the diagnosis, no further evidence is really needed!  In reality this rarely happens.  It is recommended to get an MRI for further documentation and as a baseline.  The dilemma occurs when the MRI is normal or very atypical.  It takes a very confident neurologist to make the diagnosis at this point.  this is the topic of a huge amount of discussion on the forum.

2nd Scenario

2 attacks
1 clinical lesion

The patient has had 2 or more clear-cut clinical attacks, by history, separated by remission.  The doctor has found only one clinical lesion, that is one neurologic abnormality that can only be due to damage in the CNS.  This same lesion may be found during both attacks.   What the doctor knows is that there is "dissemination in time," because there have been two attacks.  What is lacking to make the diagnosis is evidence of dissemination in Space, because only one part of the CNS can be shown to be affected.  An example of this is two attacks and the only abnormality each time isoptic neuritis in the same eye.   Dissemination in space can be determined one of in three ways

    1) a  Positive MRI (see definition above)

    2) 2 or more MRI lesions that appear consistent with MS in addition to  Positive CSF findings (see above)

    3) The doctor can "wait and see" until the patient has a new attack with evidence that a new part of the brain or cord is damaged.

3rd Scenario
1 attack
2 clinical lesions

This patient has had only 1 clear attack and shows 2 abnormalities on neurologic exam that are consistent with MS.  There is evidence that the disease has attacked more than one distinct part of the central nervous system, so we're okay on Dissemination in Space.   There is no evidence that the disease has disseminated in time.  This situation qualifies for the term Clinically Isolated Syndrome with a Multifocal Presentation.   This person would qualify for early DMDs at this point, but most neurologists would want to see 2 or more MRI lesions as well before they made the decision to start early meds.  To establish the diagnosis of Definite MS, the doctor would have to wait for one of two things to happen:

    1) Positive MRI for Time requirement (see above)


    2) "Wait and see" for a second clinical attack.  Remember that an attack must include objective evidence of damage.

4th Scenario
1 attack
1 clinical lesion

The patient has had only one clinical attack.  The doctor finds clinical evidence of 1 lesion on the neurologic exam.  This is also called a Clinically Isolated Syndrome.  In order to make a diagnosis of Definite MS, the doctor must find evidence that there is both dissemination of space of the disease AND must also find evidence that there has been dissemination in time.  The MRI and the LP become very important in this case, because there is no pattern of Relapsing andRemitting.


Note:  At this point the patient has a Clinically Isolated Syndrome with a monosymptomatic presentation.  The decision to treat early with DMDs may be made here.

Dissemination in Space can be shown by

  • Positive MRI (see definition above for (Space)


  • 2 or more MRI-detected lesions consistent with MS in addition to  Positive CSF results  (see above)

Dissemination in Time can be shown by

  • Positive MRI ( acording to the chart above for Time)


  • The doctor can "wait and see" for the patient to have a second clinical attack

Note:  At this point with both time and space requirements fulfilled the patient can be diagnosed with Definite MS.  Note that quite a bit of time may need to pass (sometimes many years) before one of the requirements above is taken care of.

5th Scenario
Insidious neurological progression of symptoms and signs suggestive of MS

These patients present the hardest case for the doctor.  They do not have the clear-cut attacks and remissions of the RRMS patients, so their history looks much like other chronic neurologic diseases.  The doctor must rely on long-term deterioration and accrual of disability.  In this case spinal lesions and a positive CSF become more important.  In fact, the two of them together can substitute for brain lesions.  In PPMS the majority of the disease is often found in the spinal cord.  But the spinal fluid does not have to be positive as it was required to be by the first McDonald Criteria.   This is in acknowledgement that there seems to be less inflammatory disease in PPMS, thus less of a tendency to form inflammatory immune antibodies (O-Bands) The diagnostic requirements for PPMS are:

    1) One year of disease progression.  This can be done looking back at the patient's history, or by following the patient for a year and observing progression or a combination of both.


    2)  2 out of the 3 following requirements:


  • Positive Brain MRI - this would consist of 9  T2 lesions or (4 or more T2 lesions + Positive VEP)
  • Positive Spinal cord MRI with 2 or more focal T2 lesions
  • Positive CSF (either +O-Bands or +IgG Index)


Diagnosis is often an art, and doctors vary in their skill, their interpretation, their curiosity and their creativity.   It is clear that MS can be daunting to diagnose.  But, the process needed to begin the diagnosis is very clear.  The neurologist must take a thorough history and physical, doing what is possible to make a timeline of the appearance of symptoms and their course.  He/She must insert the observed "clinical lesions" into this timeline and make a judgment of whether the requirement that a disease has shown both dissemination in space and in time.  From there he is ready to assess the MRI and decide which supporting tests need to be done and which tests will help add evidence in cases that are atypical and do not fit nicely into the patterns above.


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