Diagnosis of Multiple Sclerosis (MS) requires a very careful and individualized approach, especially because MS can present with a variety of symptoms and because it can mimic a variety of different conditions. Moreover, now that there is immunomodulating therapy to help prevent the progression of symptoms in MS and its long-term disability, it is more important than ever to try to make the diagnosis as early as possible.  Also, because the diagnosis is likely to include the recommendation to take an immunomodulating drug for many years with all of its potential side effects, it is important that the diagnosis be accurate. 

The most important method in making the diagnosis of MS is a careful history and examination. When the diagnosis is made in this clinical manner, the tests are used to rule out diseases that mimic MS and to obtain baseline information to later judge therapy. In order to diagnose patients sooner and start them on therapy sooner, the neurologist is under a lot of pressure to make the diagnosis with the first clinical attack rather than waiting for multiple attacks to occur.

In 2001, new criteria were adopted for the diagnosis of multiple sclerosis.  These criteria are somewhat technical in nature but their use helps to assure the prevention of misdiagnosis. This is accomplished by including criteria to prevent over-interpretation of laboratory information and a reminder to the neurologist to consider, on a case-by-case basis, diseases that at times resemble MS. These diseases include Lyme disease, vasculitis (an inflammation of blood vessels), sarcoidosis, syphilis, and vitamin B12 deficiency, among others.

Classically, MS has been defined clinically as two or more attacks separated in time and space.  An attack is a set of neurological symptoms that come on together, usually fairly abruptly.  The neurological symptoms have to be objectively verified by the neurologist (either by exam or a visual evoked response).  Having two or more attacks in different parts of the brain (separated in space) at different times (separated in time) define MS.

If a patient gives a history of two or more attacks and the neurologist can only find objective evidence of one attack, then a diagnosis of MS can still be made with a single MRI that demonstrates dissemination in space, or an MRI with at least two lesions felt compatible with MS and a CSF (cerebral spinal fluid) analysis showing either oligoclonal bands or an increased IgG index.  Dissemination in space on a single MRI requires lesions in different parts of the brain.  The CSF change of oligoclonal bands or elevated IgG index indicates an immune response in the central nervous system.

If a patient has a single attack but clinical exam suggests two or more lesions, then the diagnosis of MS can be made by an MRI that shows dissemination in time.  Dissemination in time means a lesion on MRI more than 3 months after the attack (if enhancing, i.e. the lesion is brighter after administration of an IV agent called contrast) or two MRIs with different lesions more than 3 months apart if there is no enhancing lesion on the first scan.

The most difficult patients to assess are those with a single attack and objective evidence of only a single lesion on examination.  This is known as a "clinically isolated syndrome" (CIS).  Under the new criteria, these patients can be felt to have MS if their MRI shows dissemination in space or if they have a MRI with two or more lesions consistent with MS and positive CSF findings.  Again, the criteria attempts to balance the need to start patients on treatment who ultimately would be diagnosed as MS with the need to prevent treatment of patients who would never develop clinical MS.

Another group of patients have a form of MS that is known as primary progressive MS.  These patients do not suffer distinct attacks but rather slowly decline in their neurologic function over time.  The criteria for these patients require positive CSF, dissemination in space by MRI, and dissemination in time on MRI or continued progression for one year.