Multiple Sclerosis and Demyelinating Diseases

Diseases of the nervous system are called different names depending on which tissues of the nervous system are affected and what nature of injury occurs. When inflammation occurs for no clear reason within the brain, optic nerves, or spinal cord, the term "demyelinating disease" is used. Demyelinating refers to the affecting of the white matter of the brain. This tissue contains the connections between parts of the brain and spinal cord. Examples of these illnesses named after certain parts of the nervous system include optic neuritis, which involves the nerves to the eyes, and transverse myelitis, which involves the spinal cord in varying degrees. When these illnesses recur or continuously worsen over time, or affect additional regions of the nervous system, they are called multiple sclerosis. Sclerosis simply means a scar in the brain from the injury. 

In these illnesses, immune cells enter the brain because they perceive an abnormality. This abnormality may false, may be a mistake, or it can be due to the presence of an unknown microbe in small degrees. Regardless, the immune cells cause substantial injury on entry into the brain tissue, resulting in local disruption of function, which may be experienced as various problems.

Multiple sclerosis often means a different experience for every individual who has it. It is usually a disabling disease, even when it starts as a mild illness. This illness does not usually cause someone to die.

Treatment and Diagnosis of MS

Management of Relapses in MS

Relapses will occur to 90% of people with MS at some point. A relapse is usually defined as symptoms which are worsening over at least 24 hours, presumed to be due to MS, and not due to an infection which is causing a fever. Not all relapses require treatment. The first question is to ask whether one has such an infection prior to considering treatment of a relapse. If a bladder infection is suspected because of an increase in urgency to void, burning on urination, or odor of urine, this must be addressed by an appropriate physician. Milder relapses, such as tingling numbness, mild visual disturbances which do not disrupt reading or driving, or mild vertigo do not usually require treatment and will resolve often spontaneously. Relapses which will usually need treatment are those with significant bowel or bladder dysfunction, major difficulty with walking or balance, or vision loss. Sensation abnormalities which are very painful or involve difficulty using a limb may also benefit. 

The usual treatments for relapses, often called exacerbations, of these illness requires very high doses of corticosteroids for a few days. These medications are not muscle-building steroids, but instead have a role in calming down the immune system. Small doses may be worse than no treatment at all, and the large doses are needed to get into the brain to interrupt the cycle of immune injury and get inflammatory cells out of the brain. Such treatments have been found to be very safe and rarely associated with any long term side effects.

Traditionally, these steroid treatments were administered by intravenous infusions. More recently, trials have demonstrated to be equally effective in large quantities given by mouth; however, most physicians are unfamiliar with this treatment, and it is usually prescribed only by specialized neurologists. While the action of the treatment is immediate, improvement usually continues for many weeks. These treatments work better the more recently the relapse has occurred. A physician will usually want to establish that you have a significant relapse and prescribe the appropriate treatment.

Other treatments are occasionally used in life-threatening or severe relapses unresponsive to treatment.

Medications that modify the course of MS

Currently, 5 injectable medications are approved in the US as being safe and effective for MS to reduce relapses and risk of progressive disability. Several pill therapies are also sometimes used. Three injections are different forms of interferon-beta, a hormone used by the body to defend against viruses. One injection is an artificial protein which alters the immune response, much like an allergy shot. The other medications are stronger medications to diminish the action of the immune cells.

Weekly low dose interferon or Avonex, protects against more severe relapses and reduces time to the next relapse, especially early in the course of the disease prior to an established course of MS. Betaseron and Rebif, both multiple doses weekly of interferon, have better effect in established MS and in those with a progressive as well as relapsing component to illness. Interferons have similar side effects which resemble the symptoms of a virus. Usually these adverse symptoms diminish with each injection, cause no harm, and can mostly prevented by analgesics such as acetaminophen, ibuprofen, and naproxen. Although these medications are very safe, occasional individuals have stress on their blood or liver, requiring blood tests to monitor for this problem. Individuals usually administer these injections on their own, often with an automatic injector, although some may receive the weekly interferon in the doctor’s office. 

Copaxone, a noninterferon the allergy shot therapy, is an alternative medication to the interferons but takes 6-12 months to reach its greatest effectiveness. It has benefits on relapses and some improvement on MRI activity. Generally, the effect on MRI is not as great as that with interferons. It is however extremely safe and has virtually no side effects other than at sites of injection.

Powerful immunosuppressive medications are used for more difficult courses of MS. These include Novantrone, an approved chemotherapy agent. This drug is well tolerated but increases risks of infection, but more reliably produces improvement than any other treatment. Azathioprine and methotrexate are immunosuppressive medications available as pills, but have been used successfully alone and in combination with other therapies to improve the course of MS. These medications are rarely used as first choices in therapy due to the increased risk associated with them, and careful consideration is warranted with counseling from the physician.

Treatment of symptoms in MS

It is important to emphasize that symptoms of MS are best treated first by finding a therapy which reduces new injuries to the nervous system. However, many treatments are available to help diminish individual symptoms arising from MS. Fatigue, the most common symptom, is often difficult and requires many attempts at treatment. First, the quality of night time sleep is examined. If one does not awake feeling rested, usually the night time sleep is disturbed. Trouble getting to sleep is often helped by a sleep aid, while trouble staying asleep in the middle or latter part of the night usually responds to antidepressant medications. Individuals who snore, or have leg movements frequently, may have very disturbed sleep efficiency resulting in poorly restful sleep.

The most common fatigue in MS is excessive mid or later day fatigue. This may respond to stimulant therapies. An older stimulant, amantadine, or a newer nonnarcotic stimulant called Provigil, are proven therapies in MS. Stronger stimulants of the amphetamine family are sometimes used but require much closer supervision.

Painful sensations are common, and may respond to a variety of medications, including certain antidepressant medications such as venlafaxine or nortriptyline, anti-seizure medications such as gabapentin or carbamazepine, and nonnarcotic pain killers such as tramadol. Rarely high dose narcotic medication may be helpful, but this usually must be conducted under close supervision.

Vertigo sensations often respond to small doses of medication in the Valium family, and also to medication to deal with the nausea or motion sickness which may result. Vertigo also can be effectively treated by exercises.

Bladder dysfunction is of multiple types and can be difficult to diagnose or treat. Failure the empty to bladder, or continually keeping large amounts of urine can lead to infection and kidney injury. This may respond to medication to relax the valve on the bladder, but is also treated by self catheterization, a simple procedure of inserting a tube in the bladder to achieve effective drainage. A more common problem is urinary urgency or overactive bladder, in which the reflex to empty the bladder is overactive and not entirely under voluntary control. Antispasmodic medication for the bladder can reduce this, but can lead to difficulty emptying in some cases. Loss of urine involuntarily, or urinary incontinence, can occur for either because of failing to empty or from overactive reflexes, and in addition in women can be due to a weak pelvic floor from prior surgery or childbirth. 

Depressed mood a common occurrence in MS and presumably occurs because of damage to nerve cells which make chemicals to produce normal mood. These symptoms include changes in drive, loss of pleasure, changes in appetite, irritability, changes in sleep, and a sense of guilt, hopelessness, or desire to die. It is usually effectively treated and kept away by antidepressant medication. Depression is sometimes worsened by interferon treatment, but usually does not require stopping medication.

Sexual dysfunction can occur in MS for many reasons, too extensive to go into in a brief discussion. Many of these problems are treatable.

Spasticity refers to overactive reflexes causing stiffness or involuntary movements. This occurs when loss of voluntary control over a limb is a problem. A leg may stiffen or jerk, move slowly, or tremor uncontrollably as the reflexes fight each other. Pills are available which dampen these reflexes, and injections and surgery are available for controlling this problem when severe.

Tremor can occur in some individuals, often in the head or hands. Medication can diminish this, or in rare cases brain surgery.

Trouble with walking or balance may require aids and special training to use them to assist one in doing daily activities.

Why do people get MS?

The best simple answer is "bad luck." A more complete explanation is that why an individual develops MS is due to a combination of factors which elevated risk. In the US, about 1 in 250 people will develop MS. Most of the risk of getting MS has to do with ancestry. Having a close relative with MS elevates the risk 50 times. However, only 2-5% of children of affected parents will be diagnosed with MS. People of Northern European descent, and those who grow up farther from the equator, are more at risk. However, any person can get MS. The risk to African Americans is about ½ of that of Caucasians in the US. Despite this, most people with MS do not have an affected family member. Some families break these rules and have many affected members, but the usual situation is that MS is less of a genetic illness than diabetes, heart disease, Parkinson’s disease, or Alzheimer’s disease.

MS in some respects appears to be a consequence of an infectious disease. Numerous investigations have failed to yield a consistent relationship with a single infectious agent. However, everyone with MS has a virus known as EB. EB is a very common virus which affects almost 90% of people, and infects their immune system in a lifelong fashion. It causes mononucleosis, also known as mono. 

Most specialists who treat MS believe it occurs uncommonly at random following an infection with a common virus, leading to a disorder of the immune response which injuries the brain unnecessarily. 

Testing for multiple sclerosis

In most individuals with MS, their diagnosis is established over time and the consideration of alternative causes for their symptoms. One astonishing fact about MS, is that once an individual has a typical problem associated with MS, the risk of having MS within 15 years is 90% even if all other tests show negative findings. The gold standard of diagnosis is seeing multiple problems in the nervous system come and go without another explanation.

The most useful tests for multiple sclerosis are MR imaging of the brain and sometimes spinal cord, cerebrospinal fluid examination for abnormal immune proteins, and electrical testing such as evoked responses. Other testing is often used to exclude other potential causes of the symptoms. These tests are minimally invasive and may be repeated after a period of time (usually years) if the diagnosis is inconclusive.

Procedures

Ocular coherence tomography (OCT) scanning of optic nerve head painlessly and rapidly quantitatively measures for the existence of prior injuries to the optic nerve. The presence of these defects is very common in MS and supports the presence of disease prior to established disability.

Quantitative somatosensory testing to determine thresholds for thermal and vibration sensitivity. This testing can demonstrate slight degrees of numbness which are not detectable by normal examination.

Color vision defects can be detected by a computer driven color blind testing system. Such minor changes are indicators of optic nerve disease which is seen in MS.

Multimodality evoked potentials use multiple visual stimuli (color, movement) rather than a single (black and white) stimulus to measure visual responses. Somatosensory evoked potentials performed by highly trained technicians are helpful for demonstrating how much injury is present in the central nervous system.     

Motor evoked responses permit accurate measurement of conduction velocity in the central nervous system.  Differences between two sides indicate a typical injury such as is seen in multiple sclerosis.