Diagnosis of MS

There is no single test that unequivocally detects multiple sclerosis (MS). When faced with a patient whose symptoms, neurological exam results, and medical history suggest MS, physicians use a variety of tools to rule out other possible disorders and perform a series of laboratory tests which, if positive, confirm the diagnosis.

Imaging technologies such as Magnetic Resonance Imaging (MRI) can help locate central nervous system lesions resulting from myelin loss. MRI is painless, non-invasive, and does not expose the body to radiation. It is often used in conjunction with the contrast agent gadolinium, which helps distinguish new plaques from old. However, since these lesions can also occur in several other neurological disorders, they are not absolute evidence of MS.

Several new MRI techniques may help quantify and characterize MS lesions that are too subtle to be detected using conventional MRI scans. While standard MRI provides an anatomical picture of lesions, magnetic resonance spectroscopy (MRS) yields information about the brain’s biochemistry – specifically, it can measure the brain chemical N-acetyl aspartate. Decreased levels of this chemical can indicate nerve damage.

Magnetization transfer imaging (MTI) is able to detect white matter abnormalities before lesions can be seen on standard MRI scans by calculating the amount of “free” water in tissues. Demyelinated tissues and damaged nerves show increased levels of free” (versus “bound”) water particles.

Diffusion-tensor magnetic resonance imaging (DT-MRI or DTI) measures the random motion of water molecules. Individual water molecules are constantly in motion, colliding with each other at extremely high speeds. This causes them to spread out, or diffuse. DT-MRI maps this diffusion to produce intricate, three dimensional images indicating the size and location of demyelinated areas of the brain. Changes in this process can then be measured and correlated with disease progression.

Functional MRI (fMRI) uses radio waves and a strong magnetic field to measures the correlation between physical changes in the brain (such as blood flow) and mental functioning during the performance of cognitive tasks.

In addition to helping scientists and physicians better understand how MS develops – an important first step in devising new treatments – these approaches offer earlier diagnosis and enhance efforts to monitor disease progression and the effects of treatment.

Other tests that may be used to diagnosis MS include visual evoked potential (VEP) tests and studies of cerebrospinal fluid (the colorless liquid that circulates through the brain and spinal cord). VEP tests measure the speed of the brain’s response to visual stimuli. VEP can sometimes detect lesions that the scanners miss and is particularly useful when abnormalities seen on MRI do not meet the specific criteria for MS. Auditory and sensory evoked potentials have also been used in the past, but are no longer believed to contribute significantly to the diagnosis of MS. Like imaging technologies, VEP is helpful but not conclusive because it cannot identify the cause of lesions.

Examination of cerebrospinal fluid can show cellular and chemical abnormalities often associated with MS. These abnormalities include increased numbers of white blood cells and higher than average amounts of protein, especially myelin basic protein (MBP) and an antibody called immunoglobulin G (IgG). Physicians can use several different laboratory techniques to separate and graph the various proteins in people with MS and their cerebrospinal fluid. This process often identifies the presence of a characteristic pattern called oligoclonal bands.

While it can still be difficult for the physician to differentiate between an MS attack and symptoms that can follow a viral infection or even an immunization, our growing understanding of disease mechanisms and the expanded use of MRI is enabling physicians to diagnose MS with far more confidence than ever before. Most people with MS undergo a diagnostic evaluation for MS that will be classified as either having MS or not having MS, although there are still cases where a person may have the clinical symptoms of MS but not meet all the criteria to confirm a diagnosis of MS. In these cases, a diagnosis of “possible MS” is used.

A number of other diseases may produce symptoms similar to those seen in MS. Other conditions with an intermittent course and MS-like lesions of the brain’s white matter include:

• Polyarteritis.
• Lupus erythematosus.
• Syringomyelia.
• Tropical spastic paraparesis.
• Some cancers.
• Certain tumors that compress the brainstem or spinal cord.

Progressive multifocal leukoencephalopathy can mimic the acute stage of an MS attack. Physicians will also need to rule out stroke, neurosyphilis, spinocerebellar ataxias, pernicious anemia, diabetes, Sjogren’s disease, and vitamin B12 deficiency. Acute transverse myelitis may signal the first attack of MS, or it may indicate other problems such as infection with the Epstein-Barr or herpes simplex B viruses. Recent reports suggest that the neurological problems associated with Lyme Disease may present a clinical picture much like MS.

Investigators are continuing their search for a definitive test for MS. Until one is developed, however, evidence of both multiple attacks and central nervous system lesions must be found before a diagnosis of MS is given.

Treatment for MS

There is as yet no cure for Multiple Sclerosis (MS). Many people with MS do well with no therapy at all, especially since many medications have serious side effects and some carry significant risks. Naturally occurring or spontaneous remissions make it difficult to determine therapeutic effects of experimental treatments – however, the emerging evidence that MRIs can chart the development of lesions is already helping scientists evaluate new therapies.

In the past, the principal medications physicians used to treat MS were steroids possessing anti-inflammatory properties – these include:

• Adrenocorticotropic Hormone (better known as ACTH).
• Prednisone.
• Prednisolone.
• Methylprednisolone.
• Betamethasone.
• Dexamethasone.

Studies suggest that intravenous (IV) methylprednisolone may be superior to the more traditional intravenous ACTH for people with MS who experience acute relapses – no strong evidence exists to support the use of these drugs to treat progressive forms of MS. There is some indication that steroids may be more appropriate for people with movement, rather than sensory, symptoms.

While steroids do not affect the course of MS over time, they can reduce the duration and severity of attacks in some people. The mechanism behind this effect is not known – one study suggests the medications work by restoring the effectiveness of the blood/brain barrier. Because steroids can produce numerous adverse side effects (acne, weight gain, seizures, psychosis), they are not recommended for long term use.

One of the most promising MS research areas involves naturally occurring antiviral proteins known as interferons. Three forms of beta interferon (Avonex, Betaseron, and Rebif) have now been approved by the Food and Drug Administration for treatment of relapsing-remitting MS. Beta interferon has been shown to reduce the number of exacerbations and may slow the progression of physical disability. When attacks do occur, they tend to be shorter and less severe. In addition, MRI scans suggest that beta interferon can decrease myelin destruction.

Investigators speculate that the effects of beta interferon may be due to the drug’s ability to correct an MS-related deficiency of certain white blood cells that suppress the immune system and / or its ability to inhibit gamma interferon, a substance believed to be involved in MS attacks. Alpha interferon is also being studied as a possible treatment for MS. Common side effects of interferons include:

• Fever.
• Chills.
• Sweating.
• Muscle aches.
• Fatigue.
• Depression.
• Injection site reactions.

Scientists continue their extensive efforts to create new and better therapies for MS. Goals of therapy are threefold: to improve recovery from attacks, to prevent or lessen the number of relapses, and to halt disease progression.

MS Symptoms That Are Treatable

While some scientists look for therapies that will affect the overall course of the disease, others are searching for new and better medications to control the symptoms of Multiple Sclerosis (MS) without triggering intolerable side effects.

Many people with MS have problems with spasticity, a condition that primarily affects the lower limbs. Spasticity can occur either as a sustained stiffness caused by increased muscle tone or as spasms that come and go, especially at night. It is usually treated with muscle relaxants and tranquilizers.

• Baclofen (Lioresal), the most commonly prescribed medication for this symptom, may be taken orally or, in severe cases, injected into the spinal cord.
• Tizanidine (Zanaflex), used for years in Europe and now approved in the United States, appears to function similarly to Baclofen.
• Diazepam (Valium), Clonazepam (Klonopin), and Dantrolene (Dantrium) can also reduce spasticity.

Although its beneficial effect is temporary, physical therapy may also be useful and can help prevent the irreversible shortening of muscles known as contractures. Surgery to reduce spasticity is rarely appropriate in MS.

Weakness and ataxia (incoordination) are also characteristic of MS. When weakness is a problem, some spasticity can actually be beneficial by lending support to weak limbs. In such cases, medication levels that alleviate spasticity completely may be inappropriate. Physical therapy and exercise can also help preserve remaining function, and people with MS may find that various aids-such as foot braces, canes, and walkers-can help them remain independent and mobile. Occasionally, physicians can provide temporary relief from weakness, spasms, and pain by injecting a drug called phenol into the spinal cord, muscles, or nerves in the arms or legs. Further research is needed to find or develop effective treatments for MS-related weakness and ataxia.

Although improvement of optic symptoms usually occurs even without treatment, a short course of treatment with intravenous methylprednisolone (Solu-Medrol) followed by treatment with oral steroids is sometimes used. A trial of oral prednisone in people with visual problems suggests that this steroid is not only ineffective in speeding recovery but may also increase the persons risk for future MS attacks. Curiously, prednisone injected directly into the veins – at ten times the oral dose – did seem to produce short term recovery. Because of the link between optic neuritis and MS, the study’s investigators believe these findings may hold true for the treatment of MS as well. A follow up study of optic neuritis in people will address this and other questions.

Fatigue, especially in the legs, is a common symptom of MS and may be both physical and psychological. Avoiding excessive activity and heat are probably the most important measures people can take to counter physiological fatigue. If psychological aspects of fatigue such as depression or apathy (a lack of emotion or interest, without feeling) are evident, antidepressant medications may help. Other drugs that may reduce fatigue in some people, but not all, include amantadine (Symmetrel), pemoline (Cylert), and the still – experimental drug aminopyridine.

People with MS may experience several types of pain. Muscle and back pain can be helped by aspirin or acetaminophen and physical therapy to correct faulty posture and strengthen and stretch muscles. The sharp, stabbing facial pain known as trigeminal neuralgia is commonly treated with carbamazapine or other anticonvulsant drugs or, occasionally, surgery. Intense tingling and burning sensations are harder to treat. Some people get relief with antidepressant drugs, others may respond to electrical stimulation of the nerves in the affected area. In some cases, the physician may recommend codeine.

As the disease progresses, some people with MS develop bladder malfunctions. Urinary problems are often the result of infections that can be treated with antibiotics. A doctor may recommend that people take vitamin C supplements or drink cranberry juice, as these measures acidify urine and may reduce the risk of further infections. Several medications are also available. The most common bladder problems encountered by people with MS are urinary frequency, urgency, or incontinence. A small number of people with MS retain large amounts of urine. In these people, catheterization may be necessary. In this procedure, a catheter or drainage tube is temporarily inserted (by the patient or a caretaker) into the urethra several times a day to drain urine from the bladder. Surgery may be indicated in severe, intractable cases. Scientists have developed a “bladder pacemaker” that has helped people with urinary incontinence in preliminary trials. The pacemaker, which is surgically implanted, is controlled by a hand held unit that allows the patient to electrically stimulate the nerves that control bladder function.

People with urinary problems may be reluctant to drink enough fluids, leading to constipation. Drinking more water and adding fiber to the diet usually alleviates this condition. Sexual dysfunction may also occur, especially in people with urinary problems. Men may experience occasional failure to attain an erection. Penile implants, injection of the drug papaverine, and electrostimulation are techniques used to resolve the problem. Women may experience insufficient lubrication or have difficulty reaching orgasm – in these cases, vaginal gels and vibrating devices may be helpful. Counseling is also beneficial, especially in the absence of urinary problems, since psychological factors can also cause these symptoms. For instance, depression can intensify symptoms of fatigue, pain, and sexual dysfunction. In addition to counseling, the physician may prescribe antidepressant or antianxiety medications. Amitriptyline is used to treat laughing / weeping syndrome.

Tremors are often resistant to therapy, but can sometimes be treated with drugs or, in extreme cases, surgery. Investigators are currently examining a number of experimental treatments for tremor.

Source: www.ninds.nih.gov – September 1996