Diagnosis and Lab Technology

MS Diagnosis

When diagnosing individuals with RRMS, physicians look for more than one episode of neurologic dysfunction. Later in life, RRMS often becomes progressive (SPMS). PPMS does not have separate episodes (relapses, exacerbations), and doctors must look for a progressive course of at least six months. Typically lab studies will need to be conducted, allowing the doctor to gain additional evidence for MS and to exclude other illnesses. The MRI is usually very helpful in diagnosing MS.

Initially, MS may be termed "possible" while one waits for a definite diagnosis. Symptoms that suggest MS, particularly in a young adult, include decreased vision, numbness, fatigue, sensitivity to heat, and Lhermitte's sign.

Before any diagnosis can be made, however, the physician must exclude other conditions. To diagnose MS or any other similar condition, various tests, scans, and grading systems are used to evaluate presenting symptoms and subclinical (without symptoms) disease activity.

Kurtzke Expanded Disability Status Scale and Functional System

Doctors have several measures available to them to help assess a patient's condition. These scales, indexes, tests, and profiles are aimed at giving doctors a precise measurement of a patient's present degree of ability and impairment, in such areas as mobility, strength, coordination, cognition, vision, speech, and other functions.

Through these universally accepted systems of measurement, physicians can record their patients' presenting condition and subsequent improvements, relapses, or disease progression. These systems are particularly valuable to clinical trials. They allow for drugs under development to be scientifically measured for improvements or deterioration in the treated group versus the control group. Without such measures, evaluations of treatment success or failure would be more subjective and prone to error.

The most widely known scale among the MS community is the Kurtzke Expanded Disability Status Scale (EDSS). A man named Kurtzke first introduced this system in 1955 as the Disability Status Scale. It used whole numbers from one to 10 to measure degree of disability, largely in terms of mobility. Zero denoted a normal neurologic exam; lower numbers (roughly one to six) were associated with mild to moderate symptoms; higher numbers (roughly seven to nine) referred to more severe disability, and 10 denoted that the patient was no longer living.

To make the measurements more sensitive, Kurtzke "expanded" the scale by adding half-points between the numbers. The EDSS is used in conjunction with Kurtzke's Functional System (FS). This measures the function of eight major systems in the CNS, each relating to the different areas of functioning that can be affected by MS (such as movement, sensory, bowel and bladder, vision, cognition, etc.).These are each graded on a scale of zero (normal) to six (severe).

The EDSS and FS have been instrumental in the development of treatments for MS. They also play a crucial role in diagnosis, treatment regimens, and overall patient care.

A newer measurement system is the MS Functional Composite Scale. This is hoped to be even more sensitive than the EDSS and FS, by measuring ability to walk (ambulation), upper extremity function (through the nine-hole peg test), and cognitive function, using the Paced Auditory Serial Additions Test (PASAT).

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is a great tool for the diagnosis of and clinical trials for MS. It has the ability to provide pictures of the internal progression of the disease in an individual. The MRI consists of a computer, radiofrequency stimulator, and large electromagnet.

The MRI is far more successful in detecting damage from MS than any other device to date. Repeating MRI exams at timed intervals, such as every six months, may allow for swift and accurate evaluation of a treatment's success over the course of a relatively short amount of time (several months versus several years).

The MRI of the brain has been used in the diagnosis of MS for nearly 20 years. It has greatly improved the accuracy rate for diagnosing MS, and has also helped physicians and researchers to understand the progression of the disease. Through MRI, doctors may determine the extent of new lesions, lesion burden, and overall disease activity. MS activity is often "subclinical," which means that while the disease is active on the MRI, the patient is not experiencing symptoms.

On MRI scans, physicians must look for the "dissemination of lesions in space and time" before giving a diagnosis of definite MS. They need evidence of lesions in more than one part of the white matter in the CNS.

The International Panel on MS Diagnosis has revised the criteria for identifying MS. Known as the "McDonald Criteria," these new guidelines focus on dissemination of lesions in both time and space, utilizing MRI findings that are integrated with clinical and other diagnostic techniques. These help to confirm MS diagnosis in those with a variety of presenting symptoms, so physicians may determine if a patient: (1) has MS, (2) has possible MS, or (3) does not have MS.

Sometimes a spinal MRI or evoked-potential testing (visual and somatosensory) will help provide evidence of a second lesion needed to confirm the diagnosis. Also, a second MRI may show a lesion that was not present on the earlier MRI, making it "disseminated in time."

T2-weighted MRI scans show a number of pathological changes, such as inflammation, edema, demyelination, gliosis, and axonal damage. T1-weighted MRI scans with gadolinium enhancement have the ability to show active lesions and areas where the BBB has been disrupted. Gadolinium is a contrast agent that is injected into the patient's bloodstream to help identify new activity via breakdown in the BBB.

Using the MRI as an outcome measure in clinical trials for MS provides many advantages. It gives researchers immediate feedback regarding a person's disease activity before, during, and after the trial. The MRI also gives measurable and reproducible results to determine treatment efficacy. The MRI is highly sensitive in detecting disease activity, which is five to 10 times more frequent than clinical relapses.

An MRI is obtained when possible, but an individual may also be diagnosed with MS based on his or her symptoms alone. Repeating MRI scans on a routine basis is not recommended (according to a panel of MS experts), unless it is needed to help decide on a change in treatment. Some neurologists, however, order MRI scans every one to three years as part of the ongoing care and assessment of their MS patients.

Evoked Potentials

Evoked potentials help to point out lesions that are not causing symptoms by providing evidence of slowed nerve impulses. Visual evoked potentials measure the speed and amplitude of nerve impulses along the visual pathway. This is a noninvasive test, which uses an electrode placed on the back of the head to record cortical (outer layer) signals. The person being tested is shown a visual stimulus - usually a reversing checkerboard pattern - and the electrode records when the nerve impulse is received.

Somatosensory evoked potentials pertain to sensations in skin and deep tissue. These measure the conduction of impulses by applying electrical stimulus to the arms and legs, while electrodes record neural signals when they reach the scalp.

Brainstem and auditory evoked potentials (for hearing) may also be conducted. While evoked potentials can detect a slowing of nerve impulses in the absence of symptoms (denoting an abnormality), the MRI is now more commonly used to find subclinical evidence of disease activity.

Magnetic Resonance Spectroscopy

A device similar to the MRI is the magnetic resonance spectroscopy (MRS), which is used to measure chemical changes in the brain. This can provide information on axonal damage or loss in MS lesions, as well as identify early markers in lesion development. The MRS is not routinely performed, but is particularly useful in clinical trials of new agents.

Cerebrospinal Fluid Analysis

Cerebrospinal fluid (CSF) analysis is occasionally recommended to look at disease activity or to provide further evidence for diagnosis. Since the MRI, this procedure is used less often. In people with MS, CSF analysis frequently shows oligoclonal immunoglobulin, which indicates abnormal antibody production.
In order to conduct CSF analysis, a spinal tap must be performed. A local anesthetic is given and a needle is inserted in the space between the bones of the spine in the lower back. A small amount of CSF is collected into the needle.