Dr. Timothy L. Vollmer
Chairman, Division of Barrow Neurology

Director, Barrow NeuroImmunology Program

Barrow Neurological Institute
St. Joseph's Hospital and Medical Center
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Timothy L. Vollmer M.D.
Director, Barrow NeuroImmunology Program
Barrow Neurological Institute
St. Joseph's Hospital and Medical Center

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For Broadband Users Runtime: 4:17 WMV
For Broadband Users Runtime: 4:17 WMV
Timothy L. Vollmer M.D.
Director, Barrow NeuroImmunology Program
Barrow Neurological Institute
St. Joseph's Hospital and Medical Center

Runtime: 54 sec
Runtime: 54 sec
Susan N. Rhodes
Multiple Sclerosis Research
Barrow Neurological Institute

Chris Uithoven
National Multiple Sclerosis Society
Arizona Chapter

Jerry Turner
Program Director
National Multiple Sclerosis Society
Arizona Chapter

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CLEVELAND CLINIC: CLICK TO READ MORE"Multiple sclerosis is not a disease that is easily diagnosed. Unfortunately, there is no one symptom that indicates MS, nor is there a single test that diagnoses MS. A diagnosis of MS is made after a complete review of the patient’s medical history, a neurological examination (including function of the brain and spinal cord) and diagnostic tests such as a MRI, spinal tap and/or evoked potentials.

Criteria for Diagnosing MS

There is evidence of plaques (lesions) in at least two separate areas of the CNS;

A course following one of two patterns: two or more episodes lasting at least 24 hours and occurring at least one month apart, or a progressive course of signs and symptoms over at least six months;

There must be no other reasonable explanation of the plaque formation and symptoms.

Magnetic Resonance Imagining (MRI)
a test that produces very clear pictures, or images, of the human body without the use of x-rays.

Spinal Tap (lumbar puncture)
a test done to remove a sample of spinal fluid from the spinal column.

Evoked Potentials
a test that measures your brain’s response to certain types of stimulation, such as watching a pattern on a video screen, hearing a series of clicks, or receiving electrical impulses in your arm or leg.

How Is MS Diagnosed?
An accurate diagnosis is based on your medical history and neurological examination. A variety of specialized procedures are helpful in accurately diagnosing MS. These procedures may include a MRI (magnetic resonance imaging), spinal tap, evoked potentials, or other laboratory analysis of blood samples.

What does a MRI Show?
The images produced by a MRI gives neurologists clear evidence of scar tissue in the deep parts of the brain and/or spinal cord that is characteristic of MS. However, abnormal spots on the brain MRI can be caused by other conditions. To ensure the proper diagnosis of MS, it is important that a qualified neurologist interpret these images.

Will I need a Spinal Tap?
Performing a spinal tap (lumbar puncture) is done to examine the cerebrospinal fluid. Cerebrospinal fluid is tested for levels of certain immune system proteins and the presence of oligoclonal bands. For some individuals a spinal tap is done in order to rule out other medical conditions and support the diagnosis of MS.

What other tests might be done?
Evoked potentials are helpful in confirming whether MS has affected the visual, auditory, or sensory pathways. Evoked potentials are used to measure the electrical activity in certain areas of the brain and spinal cord. Electrical activity is produced by stimulation of specific sensory nerve pathways. These tests are used in combination with other diagnostic tools to assist in the diagnosis of multiple sclerosis (MS) and other disorders. Evoked potentials are used because they can indicate dysfunction along nerve pathways that is too subtle to show up during a neurologic examination or noticed by the person. The disruption may not even be visible on MRI. Evoked potentials test and record how quickly and completely the nerve signals reach the brain.

Your doctor may order blood tests to help rule out conditions that imitate multiple sclerosis, but the presence of MS cannot be detected in the blood.

The Future
The diagnosis of multiple sclerosis can be a lengthy process. Upon hearing the diagnosis, you may feel a mixture of emotions such as denial, relief, fear, and optimism.
When a person develops MS, he or she wants to know what will happen in the future. One of the greatest challenges of MS is the unpredictability and uncertainty of what is to come. A good plan for coping with what may come is to:

Educate yourself about the disease and any possible changes;

Work with your doctor and other health care professionals to manage your symptoms and general health;

Communicate openly with your family and others;

Stay healthy by eating properly, getting plenty of rest, exercise (when you can) and find healthy coping techniques to manage stress."




NATIONAL MS SOCIETY: CLICK TO READ MORE"At this time, no single test is available to identify or rule out MS. Several tests and procedures are needed. These are likely to include:

Complete Medical History
Healthcare providers need an overall view of the individual's health picture, including symptoms and when they began.

Nervous System Functioning
Testing of reflexes, balance, coordination, and vision— as well as checking for areas of numbness

Diagnostic Tests such as:

MRI scan, which gives detailed view of the brain
Evoked potential tests, which measure how quickly and accurately a person's nervous system responds to certain stimulation
Spinal tap, which checks spinal fluid for signs of the disease

Two Basic Signs are Required to Confirm MS

1. Signs of disease in different parts of the nervous system
2. Signs of at least two separate flare-ups (also called relapses or exacerbations) of the disease"



UNIVERSITY OF MARYLAND MEDICAL CENTER: CLICK TO READ MORE"In 2001 an international panel of experts recommended criteria, called the McDonald criteria, for diagnosing multiple sclerosis in early stages. They use the presence of specific symptoms, spinal fluid evaluation, and advances in magnetic resonance imaging for detecting lesions within the central nervous system and tracking them over time. The criteria are showing high reliability in identifying MS in patients with a variety of disease stages or states, including having only one episode (known as a clinically isolated syndrome), having a typical relapsing-remitting course, or having a slow insidious progression without clear attacks or remissions. Depending on the MRI and other findings, the patient is then categorized as having MS, possible MS, or no MS.

Ruling Out Other Disorders

The symptoms of MS are similar to a number of other diseases, which must be ruled out. These include stroke, alcoholism, emotional disorders, Lyme disease, chronic fatigue syndrome, fibromyalgia, AIDS, and certain other autoimmune disorders (e.g., scleroderma, Sjögren's syndrome, and systemic lupus erythematosus).

Expanded Disability Status Scale

Presently physicians and investigators generally use a test called the Expanded Disability Status Scale (EDSS) to rate the severity of symptoms. It is also used after a diagnosis to gauge status of the disease, and score the effectiveness of treatments. The scale ranges from zero to ten with higher scores indicating more severe symptoms. These are subjective ratings that require physician observation skills. [See Box Multiple Sclerosis Disability Score and Disease Progression.]

Objections to the use of the EDSS are that it assesses only limp and walking problems and does not assess other important complications, including fatigue, sexual function, and mental function.

Laboratory Tests

No reliable single laboratory procedure or test can establish the diagnosis of multiple sclerosis. Several are necessary before a diagnosis can be made.

Analysis of Cerebrospinal Fluid (CFS). Obtaining a sample of spinal fluid requires a lumbar puncture, or spinal tap. Testing spinal fluid is becoming increasingly important for detecting abnormal proteins, tiny fragments of myelin, or specific white blood cells that can help in making a diagnosis. For example, high levels of the immunoglobulin IgG is useful for making a diagnosis and may be a marker for disease progression. (Immunoglobulins are protein chains that are part of the immune system.)

A lumbar puncture, or spinal tap, is a procedure to collect cerebrospinal fluid to check for the presence of disease or injury. A spinal needle is inserted, usually between the 3rd and 4th lumbar vertebrae in the lower spine. Once the needle is properly positioned in the subarachnoid space (the space between the spinal cord and its covering, the meninges), pressures can be measured and fluid can be collected for testing.

Evoked Potential (EP) Test. This is a simple and painless electrical test of nerve function that assesses how long it takes nerve impulses from the eye, ear, or skin to reach the brain.

Investigative Laboratory Tests. A urine test that can show elevated levels of a substance called myelin basic protein-like material may become a convenient, economical, noninvasive way to monitor the progression of MS. This substance becomes elevated as axonal damage occurs when the disease progresses. Certain tests for color blindness may be helpful in tracking the effect of MS on the eyes.

Click the icon to see an image of urine testing.

Click the icon to see an example of the color blindness tests.

Magnetic Resonance Imaging

Magnetic resonance imaging scans are important diagnostic tools in MS and are used for diagnosing multiple sclerosis, tracking changes over time, and helping to determine treatment effectiveness.

Click the icon to see an image of a brain MRI.

Making a Diagnosis. Magnetic resonance imaging (MRI) scans can detect patches of injured tissue (lesions) that suggest MS. (It should be noted that such lesion scans may also indicate other conditions such as infections, migraines, or clots.) A very sensitive MRI technique using enhancement by an agent called gadolinium can detect disturbances in the blood-brain barrier that may indicate an early development of lesions. To make a complete diagnosis, an experienced physician, most often a neurologist, still needs to be familiar with the symptoms of multiple sclerosis.

Detecting New or Increasing Lesions. Once diagnosed, periodic follow-up MRIs can be used to track the disease and effectiveness of treatments in two ways:

By distinguishing new lesions from old ones.
Revealing increasing or decreasing numbers of lesions within the central nervous system over time.
Detecting lesions before further symptoms appear may allow a physician to initiate early treatment that may prove beneficial. Many experts therefore now advocate performing a brain MRI as soon as symptoms appear. However, neither the rate nor the number of new or growing lesions necessarily predicts immediate onset or worsening of symptoms or the development of secondary progressive MS.

Measuring Atrophy in Brain and Spinal Cord. As myelin, axons, oligodendrocytes, and neurons are destroyed, the brain begins to shrink. Processing MRI images to determine brain volume may be a useful way to monitor progression and treatment effects. MRI can also detect shrinkage in the spinal cord, which is proving to be a very strong marker of disease progression.

Detecting Black Holes. Severe disease progression can be gauged by the presence of so-called "black holes." These are lesions in the brain that emit very low signals on an MRI scan. Some evidence suggests that they may represent iron deposits in the brain."



UNIVERSITY OF CALIFORNIA - SAN FRANCISCO MEDICAL CENTER: CLICK TO READ MORE"The diagnosis of MS is based upon a clinical evaluation including documentation of "symptoms" and "signs" of the disease. Symptoms are the experiences of the patient. Examples of symptoms include double vision, tingly sensations, or difficulty controlling the bladder. Signs are abnormalities found on neurological examination and must be evident to the neurologist. Examples of signs include weakness of specific muscles, hyperactive reflexes, incoordination (ataxia), and abnormal eye movements. The diagnosis of clinically definite MS requires documentation of two distinct episodes of symptoms and two or more signs evident on the neurological examination. Episodes of symptoms must last at least 24 hours and be separated by one or more months. Signs must be due to involvement of 2 or more separate parts of the brain and spinal cord. Electrophysiological tests called evoked potentials can be helpful in documenting involvement in more than one location in the CNS.

The diagnosis of MS can be difficult to establish, especially when the initial symptoms are unaccompanied by signs, abnormalities on MRI or electrophysiological tests, or analyses of spinal fluid. Even when the initial symptoms is accompanied by abnormalities on the neurological examination, it is still possible that the correct diagnosis is something other than MS. For this reason, MS is said to be a "diagnosis of exclusion". This means that other medical conditions must be considered and excluded before the diagnosis of MS can be made confidently. Medical conditions that can mimic MS include metabolic or vitamin deficiencies, unusual infections, inflammation of the blood vessels of the brain (arteritis), degenerative disorders of the nervous system, or cancers that have spread to the brain. This is why blood tests, X-rays, brain and spine MRI's, and spinal taps to analyze cerebrospinal fluid may be required before a diagnosis of MS can be made with certainty. In some cases, even after extensive testing, a confident diagnosis cannot be made and future developments must be awaited.

Diagnostic tests

Tests can facilitate the diagnosis of MS, particularly when there are fewer than two abnormal signs on the neurological examination. In this instance, an abnormal test can be used to document a second sign.

Magnetic resonance imaging (MRI): The brain MRI is the most sensitive test for detecting structural abnormalities due to MS-related disease activity. MRI scans show focal brain abnormalities in more than 90% of patients with clinically definite MS. The MRI scan can also distinguish between new or old lesions, and thus provides a measure of disease activity. The MRI is also useful for excluding other neurological conditions that might be confused with MS. Because the imaging abnormalities seen in MS patients can also be seen in other medical conditions, a diagnosis of definite MS cannot be based solely upon the MRI.

Evoked Potentials: Evoked potentials reflect changes in the electrical activity that occurs within the CNS due to sensory input (a stimulus). The electrical response to the stimulus is measured by electrodes applied to the scalp. Visual evoked potentials are obtained by stimulating the eye with a checkerboard pattern of light and dark squares that are alternated on a television monitor. Brain stem auditory evoked potentials are produced by click sounds applied through earphones. Somatosensory evoked potentials are produced by electrically stimulating nerves in the hands or feet. The time between application of the stimulus and occurrence of the evoked potential provides a measure of the nerve's ability to conduct electrical impulses from one point to another. If the response time is slowed, this suggests that the nerve pathway is not functioning properly as a result of demyelination. These tests are abnormal in 70-90% of patients with clinically definite MS and often detect abnormalities that are not apparent on neurological examination. Because these tests measure function within the brain or spinal cord, they complement the information about brain structure provided by the MRI.

Lumbar Puncture (Spinal Tap): Cerebrospinal fluid abnormalities are detected in 80-90% of patients with clinically definite MS. These abnormalities include an increase in the number of cells and immunoglobulin proteins suggesting an inflammation or a heightened immune response. This test may be used to establish a diagnosis in patients who have experienced a slowly progressive decline in function without exacerbations (i.e., patients with so-called primary progressive MS) and who have no abnormalities seen on the brain MRI scan. In such instances, a diagnosis of definite MS cannot be made without an abnormality in the spinal fluid. The spinal fluid analysis may also be useful in excluding an infection that may be difficult to distinguish from MS."



JOHNS HOPKINS HOSPITAL: CLICK TO READ MORE"Patient history and careful neurological and eye examination.

Lumbar puncture (spinal tap).

MRI (magnetic resonance imaging) to detect plaques of scar tissue even in the absence of associated symptoms.

Tests to detect abnormalities of vision and other sensory modalities.

No single diagnostic test is definitive for MS, and several attacks may occur before diagnosis is certain."



MAYO CLINIC: CLICK TO READ MORE"Multiple sclerosis can be difficult to diagnose. Your doctor may base a diagnosis of MS on the following:

Medical history. Your doctor reviews your symptoms and the pattern of the symptoms.
Neurological examination. This examination systematically tests various parts of your nervous system, including your reflexes, muscle strength, muscle tone, and sensations of pain, heat, touch and vibration. Your doctor may also observe your gait, posture, coordination and balance, and ask you questions to help determine the clarity of your thinking, judgment and memory.
Magnetic resonance imaging (MRI) scan. The cylinder-shaped MRI scanner creates tissue-slice images on a computer from data generated by a powerful magnetic field and radio waves. Your doctor can view these images from any direction or plane. This imaging technique may reveal MS lesions, which are caused by myelin loss. Newer MRI techniques can provide even greater detail.
Spinal tap (lumbar puncture). In this procedure, a doctor or nurse removes a small sample of cerebrospinal fluid from within your spinal canal for laboratory analysis. This sample can show abnormalities associated with MS, such as abnormal levels of white blood cells or proteins. This procedure can also help rule out viruses and other conditions that can cause neurological symptoms.
Evoked potential test. This test measures the electrical signals sent by the brain in response to stimuli. An evoked potential test may use visual stimuli or electrical stimuli, in which short electrical impulses are applied to the legs or arms."