Multiple Sclerosis   
Diagnostic Testing

MAGNETIC RESONANCE IMAGING, NMR OR MRI
MRI is a noninvasive painless but noisy diagnostic scan that is based on how hydrogen atoms behave when placed in a magnetic field then disturbed by radiofrequency signals. There is no exposure to radiation. An MRI can evaluate many areas of the body, not just the brain. Gadolinium (Magnevist) a contrast medium, may or may not be used. The blood appears dark on a scan and provides a natural contrast to the blood vessels. You will be asked if you have any implantable metal objects such as a pacemaker, pumps, aneurysm clips, ear implants or any metal fragments. If not, you will be asked to remove all metal objects, dental bridges, jewelry, hair clips, belts, credit cards etc. You will then be placed on a hard platform that slides into the tunnel-like magnetic field. If you are claustrophobic, you may wish to have someone else in with you to visit with. You will need to remain perfectly still. The machine is really noisy with a constant thumping so you may want to ask for ear plugs otherwise just hum a song to the beat of the thump. The scan will take from 30 to 90 minutes. Patient Prep:No dietary restrictions are necessary.
T2-weighted scans are abnormal in approximately 90% of MS patients. MRI interpretations should be conservative and correlate with the clinical findings. Typically at least 4 white matter areas of increased signal of >3 mm diameter, or 3 areas if at least 1 is periventricular, should be seen.

ALDOLASE
Aldolase is an enzyme that aids in converting glycogen into lactic acid. It exists in most tissues throughout the body. A high level may indicate muscular or liver destruction or injury. Normal levels are seen in polio, myasthenia gravis and multiple sclerosis. A valuable test to differentiate between neurologic causes of weakness and muscular causes of weakness. This is a blood test.

LUMBAR PUNCTURE OR SPINAL TAP
The dreaded tap! This is a sterile procedure involving the withdrawal of spinal fluid for analysis. The patient either sits or is positioned on their side with knees drawn up into a fetal position. He/she will be instructed to hold on to their knees to maintain the position. Lay very still. A local anesthetic is injected into the skin and tissues around the site. A spinal needle containing an inner obturator is inserted in the subarachnoid space of the spinal canal. The obturator is then removed and a few drops of spinal fluid will drip from the needle. A sterile manometer is attached to the needle and the opening pressure is measured. Five to ten ml of fluid is removed and the closing pressure is recorded. A dressing is applied and you will be placed in a prone position (face down) with a pillow under the abdomen to increase the intraabdominal pressure which will increase the pressure in the tissues surrounding the spinal cord. Drink increased amounts of fluid with a straw and stay flat. Try not to move your head. Lay flat for 12 to 24 hours. Ask if you can turn side to side as long as you don't raise your head.
The fluid is evaluated for the presence of blood, bacteria, malignant cells, glucose, protein, color, cells, chloride, lactic dehydrogenase, serology, oligoclonal gammaglobulin bands and glutamine among other things. Patient Prep: No fasting or sedation is required. You may instructed to empty your bowels and bladder before the procedure.

CEREBROSPINAL FLUID FINDINGS
Protein: Normal or mildly increased in 50%. May have an elevation of the globulin fraction of total protein. Glucose: Normal Lymphocytes: Normal in 66%. In remainder, range from 5-20 cells/mm. T/B lymphocyte ratio is 80/20. CD4+/CD8+ is 2/1. IgG: Increased in about 70% Increased IgG synthesis 3.3 mg/day in 90% of patients. High IgG index: 0.7 in 90% of patients. Oligoclonal IgG bands: 90% of cases by immunoelectrophoresis and silver staining. Light chains: Increased ratio of kappa/lambda and free kappa light chains. Myelin basic protein: Normally greater than 1 ng/ml. Increased in acute relapses to 4 ng/ml in 80% of cases.

EVOKED POTENTIALS
VISUAL EVOKED RESPONSES or VERs is a painless test used to detect plaques in optic nerves, chiasm, or tracts. Electrodes are placed on the scalp along the vertex and the cortex lobes. You sit in front of a computer-like monitor and watch a strobe light flash or a reversible checkerboard pattern flash on the screen. This provides a visual stimulus to the eye and causes an electrical response in the occipital region of your brain that can be recorded with electrodes similar to an EKG or EEG. Electricity passes only from your brain to the machine. The machine then records the length of time it takes the signal to go from your eye to the occipital area. Abnormal responses are found in 85 to 90% of those with definite MS and 58% of those with probable MS. Interocular P latency difference is common feature. Patient Prep: Shampoo hair. No fasting required.

AUDITORY BRAINSTEM EVOKED POTENTIALS or ABEPs is a painless procedure most useful in detecting suspected lesions in the cochlear divisions of the 8th (vestibulocochlear) nerve, the auditory pathways of the brainstem. Electrodes are placed on the scalp along the vertex and on each earlobe. Ear phones are placed on the patient and a series of clicking nosies or tone bursts are played. The test is performed on both ears to detect lesions in the auditory pathway. There are abnormal responses in 67% of patients with definite MS and 41% of those with probable MS. Patient Prep: Shampoo hair. No fasting required.
SOMATOSENSORY EVOKED RESPONSES or SER's is not a painful test however it may be slightly uncomfortable. It is useful to detect sensory abnormalities. Small electrodes are placed on the scalp, each wrist (medial nerve) and the knees (peroneal nerve). It takes about 30 minutes. Electrical stimuli is applied via the electrodes and the time it takes the current to travel along the nerve to the cortex of the brain is measured. The current is small. Abnormalities are seen in 77% of patients wi th definite and 67% of patients with probable MS. Patient Prep: Shampoo hair. No fasting required.


GUIDELINES FOR DIAGNOSES
CLINICALLY DEFINITE MS: There must be evidence from both history and neurologic examination of more than one lesion or history of two episodes, signs of one lesion on examination, and abnormal evoked responses, MRI or other lesions. It should be of a consistent course a relapsing, remitting course with at least 2 episodes separated by four to six weeks. There should be a slow or stepwise progression for at least 6 months with documented neurologic signs of lesions in more than one site, of brain or spinal cord white matter. Onset of symptoms between ages 10 and 50 years. No better neurologic explanations.
LABORATORY-SUPPORTED DEFINITE MS: There must be evidence of two lesions either in history or examination. If only one lesion is evident in the history or examination, an additional lesion must be evident in evoked response or MRI. Spinal fluid IgG content and pattern should be abnormal.
PROBABLE: There will be a history of relapsing, remitting symptoms but symptoms not documented. There will be one symptom present commonly associated with MS. The episode will result in good recovery, then variable symptoms and signs. No better neurologic explanation.
POSSIBLE: There will be a history of relapsing, remitting symptoms without documentation of signs. Objective symptoms will be insufficient to establish more than one lesion of central white matter. No better neurologic explanation.

DIFFERENTIAL DIAGNOSIS OF MULTIPLE SCLEROSIS
Acute disseminated encephalomyelitis (ADEM) Lyme disease HIV-associated myelopathy HTLV-I meylopathy Neurosyphilis Progressive multifocal leukoencephalopathy Systemic lupus erythematosus Polyarteritis nodosa Sjogren syndrome Behcet disease Sarcoidosis Paraneoplastic syndromes Subacute myelo-optic neuritis Adrenomyeloneuropathy Spinocerebellar syndromes Hereditary spastic paraparesis/primary lateral sclerosis Miscellaneous: Strokes, tumors, arteriovenous malformations, arachnoid cysts, Arnold-Chiari malformations, and cervical spondylosis all may lead to diagnostic dilemmas on occasion. These conditions may co-exist; differentiation based on history, clinical follow-up and MRI features.



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