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Multiple sclerosis (MS) involves an immune-mediated process in which an abnormal response of the body’s immune system is directed against the central nervous system (CNS). The CNS is made up of the brain, spinal cord and optic nerves.
Within the CNS, the immune system causes inflammation that damages myelin — the fatty substance that surrounds and insulates the nerve fibers — as well as the nerve fibers themselves, and the specialized cells that make myelin.
When myelin or nerve fibers are damaged or destroyed in MS, messages within the CNS are altered or stopped completely.
Damage to areas of the CNS may produce a variety of neurological symptoms that will vary among people with MS in type and severity.
The damaged areas develop scar tissue which gives the disease its name – multiple areas of scarring or multiple sclerosis.
The cause of MS is not known, but it is believed to involve genetic susceptibility, abnormalities in the immune system and environmental factors that combine to trigger the disease.
People with MS typically experience one of four disease courses (types of MS). There are over a dozen treatments to help modify the MS disease process.
At this time, there are no symptoms, physical findings or laboratory tests that can, by themselves, determine if you have MS. Several strategies are used to determine if you meet the long-established criteria for a diagnosis of MS, and to rule out other possible causes of whatever symptoms you are experiencing. These strategies include a careful medical history, a neurologic exam and various tests including magnetic resonance imaging (MRI), spinal fluid analysis, and blood tests to rule out other conditions.
Timely and accurate diagnosis
There are many possible causes of neurological symptoms. When MS is considered as a potential diagnosis, other causes must be excluded — through the tools and tests outlined below — before an MS diagnosis is considered definitive. While this process of exclusion may be quick for some, it can also take much longer, with repeat testing sometimes needed. Making the diagnosis of MS as quickly and accurately as possible is important for several reasons:
You are living with frightening and uncomfortable symptoms and need to know the reason for your discomfort. Getting the diagnosis allows you to begin the adjustment process and relieves worries about other diseases such as cancer.
Since we now know that permanent neurologic damage can occur even in the earliest stages of MS, it is important to confirm the diagnosis so that you can start the appropriate treatment(s) as early in the disease process as possible.
Criteria for a diagnosis of MS
At this time, there are no symptoms, physical findings or laboratory tests that can — by themselves — determine if you have MS. The doctor uses several strategies to determine if you meet the MS diagnostic criteria. In order to make a diagnosis of MS, the physician must:
Find evidence of damage in at least two separate areas of the central nervous system (CNS), which includes the brain, spinal cord and optic nerves AND
Find evidence that the damage occurred at different points in time AND
Rule out all other possible diagnoses
The Revised McDonald Criteria, published In 2017 by the International Panel on the Diagnosis of Multiple Sclerosis, include specific guidelines for using MRI and cerebrospinal fluid analysis to speed the diagnostic process. The MRI can be used to look for a second area of damage in a person who has experienced only one attack (also called a relapse or an exacerbation) of MS-like symptoms — referred to as clinically-isolated syndrome (CIS). The MRI can also be used to confirm that damage has occurred at two different points in time. In some circumstances, the presence of oligoclonal bands in a person's cerebrospinal fluid analysis can be used instead of dissemination in time to confirm the MS diagnosis
Tools for making a diagnosis
Medical history and neurologic exam
Your healthcare provider:
Takes a careful history to identify any past or present symptoms that might be caused by MS.
Gathers information about birthplace, family history, environmental exposures, history of other illnesses and places traveled that might provide further clues.
Performs a comprehensive neurologic exam, which includes tests of cranial nerves (vision, hearing, facial sensation, strength, swallowing), sensation, reflexes, coordination, walking and balance.
In many instances, medical history and neurologic exam provide enough evidence to meet the diagnostic criteria. Other tests are used to confirm the diagnosis or to identify other possible causes of the symptoms or neurological exam findings.
While there is no definitive blood test for MS, blood tests can rule out other conditions that cause symptoms similar to those of MS, including lupus erythematosis, Sjogren's, vitamin and mineral deficiencies, some infections, and rare hereditary diseases.
There is no cure for multiple sclerosis. Treatment typically focuses on speeding recovery from attacks, slowing the progression of the disease and managing MS symptoms. Some people have such mild symptoms that no treatment is necessary.
Treatments for MS attacks
Corticosteroids, such as oral prednisone and intravenous methylprednisolone, are prescribed to reduce nerve inflammation. Side effects may include insomnia, increased blood pressure, increased blood glucose levels, mood swings and fluid retention.
Plasma exchange (plasmapheresis). The liquid portion of part of your blood (plasma) is removed and separated from your blood cells. The blood cells are then mixed with a protein solution (albumin) and put back into your body. Plasma exchange may be used if your symptoms are new, severe and haven't responded to steroids.
Treatments to modify progression
For primary-progressive MS, ocrelizumab (Ocrevus) is the only FDA-approved disease-modifying therapy (DMT). Those who receive this treatment are slightly less likely to progress than those who are untreated.
For relapsing-remitting MS, several disease-modifying therapies are available.
Much of the immune response associated with MS occurs in the early stages of the disease. Aggressive treatment with these medications as early as possible can lower the relapse rate, slow the formation of new lesions, and potentially reduce risk of brain atrophy and disability accumulation.
Many of the disease-modifying therapies used to treat MS carry significant health risks. Selecting the right therapy for you will depend on careful consideration of many factors, including duration and severity of disease, effectiveness of previous MS treatments, other health issues, cost, and child-bearing status.
Treatment options for relapsing-remitting MS include injectable and oral medications.
Injectable treatments include:
Interferon beta medications.These drugs are among the most commonly prescribed medications to treat MS. They are injected under the skin or into muscle and can reduce the frequency and severity of relapses.
Side effects of interferons may include flu-like symptoms and injection-site reactions.
You'll need blood tests to monitor your liver enzymes because liver damage is a possible side effect of interferon use. People taking interferons may develop neutralizing antibodies that can reduce drug effectiveness.
Glatiramer acetate (Copaxone, Glatopa). This medication may help block your immune system's attack on myelin and must be injected beneath the skin. Side effects may include skin irritation at the injection site.
Oral treatments include:
Fingolimod (Gilenya). This once-daily oral medication reduces relapse rate.
You'll need to have your heart rate and blood pressure monitored for six hours after the first dose because your heartbeat may be slowed. Other side effects include rare serious infections, headaches, high blood pressure and blurred vision.
Dimethyl fumarate (Tecfidera). This twice-daily oral medication can reduce relapses. Side effects may include flushing, diarrhea, nausea and lowered white blood cell count. This drug requires blood test monitoring on a regular basis.
Diroximel fumarate (Vumerity). This twice-daily capsule is similar to dimethyl fumarate but typically causes fewer side effects. It's approved for the treatment of relapsing forms of MS.
Teriflunomide (Aubagio). This once-daily oral medication can reduce relapse rate. Teriflunomide can cause liver damage, hair loss and other side effects. This drug is associated with birth defects when taken by both men and women. Therefore, use contraception when taking this medication and for up to two years afterward. Couples who wish to become pregnant should talk to their doctor about ways to speed elimination of the drug from the body. This drug requires blood test monitoring in a regular basis.
Siponimod (Mayzent). Research shows that this once-daily oral medication can reduce relapse rate and help slow progression of MS. It's also approved for secondary-progressive MS. Possible side effects include viral infections, liver problems and low white blood cell count. Other possible side effects include changes in heart rate, headaches and vision problems. Siponimod is harmful to a developing fetus, so women who may become pregnant should use contraception when taking this medication and for 10 days after stopping the medication. Some might need to have the heart rate and blood pressure monitored for six hours after the first dose. This drug requires blood test monitoring on a regular basis
Cladribine (Mavenclad). This medication is generally prescribed as second line treatment for those with relapsing-remitting MS. It was also approved for secondary-progressive MS. It is given in two treatment courses, spread over a two-week period, over the course of two years. Side effects include upper respiratory infections, headaches, tumors, serious infections and reduced levels of white blood cells. People who have active chronic infections or cancer should not take this drug, nor should women who are pregnant or breast-feeding. Men and women should use contraception when taking this medication and for the following six months. You may need monitoring with blood tests while taking cladribine.
Infusion treatments include:
Ocrelizumab (Ocrevus). This humanized monoclonal antibody medication is the only DMT approved by the FDA to treat both the relapse-remitting and primary-progressive forms of MS. Clinical trials showed that it reduced relapse rate in relapsing disease and slowed worsening of disability in both forms of the disease.
Ocrelizumab is given via an intravenous infusion by a medical professional. Infusion-related side effects may include irritation at the injection site, low blood pressure, a fever and nausea, among others. Some people may not be able to take ocrelizumab, including those with a hepatitis B infection. Ocrelizumab may also increase the risk of infections and some types of cancer, particularly breast cancer.
Natalizumab (Tysabri). This medication is designed to block the movement of potentially damaging immune cells from your bloodstream to your brain and spinal cord. It may be considered a first line treatment for some people with severe MS or as a second line treatment in others.
This medication increases the risk of a potentially serious viral infection of the brain called progressive multifocal leukoencephalopathy (PML) in people who are positive for antibodies to the causative agent of PML JC virus. People who don't have the antibodies have extremely low risk of PML.
Alemtuzumab (Campath, Lemtrada). This drug helps reduce relapses of MS by targeting a protein on the surface of immune cells and depleting white blood cells. This effect can limit potential nerve damage caused by the white blood cells. But it also increases the risk of infections and autoimmune disorders, including a high risk of thyroid autoimmune diseases and rare immune mediated kidney disease.
Treatment with alemtuzumab involves five consecutive days of drug infusions followed by another three days of infusions a year later. Infusion reactions are common with alemtuzumab.
The drug is only available from registered providers, and people treated with the drug must be registered in a special drug safety monitoring program. Alemtuzumab is usually recommended for those with aggressive MS or as second line treatment for patients who failed another MS medication.
Treatments for MS signs and symptoms
Physical therapy for multiple sclerosis
Physical therapy can build muscle strength and ease some of the symptoms of MS.
Physical therapy. A physical or occupational therapist can teach you stretching and strengthening exercises and show you how to use devices to make it easier to perform daily tasks.
Physical therapy along with the use of a mobility aid when necessary can also help manage leg weakness and other gait problems often associated with MS.
Muscle relaxants. You may experience painful or uncontrollable muscle stiffness or spasms, particularly in your legs. Muscle relaxants such as baclofen (Lioresal, Gablofen), tizanidine (Zanaflex) and cyclobenzaprine may help. Onabotulinumtoxin A treatment is another option in those with spasticity.
Medications to reduce fatigue. Amantadine (Gocovri, Osmolex), modafinil (Provigil) and methylphenidate (Ritalin) may be helpful in reducing MS-related fatigue. Some drugs used to treat depression, including selective serotonin reuptake inhibitors, may be recommended.
Medication to increase walking speed. Dalfampridine (Ampyra) may help to slightly increase walking speed in some people. People with a history of seizures or kidney dysfunction should not take this medication.
Other medications. Medications also may be prescribed for depression, pain, sexual dysfunction, insomnia, and bladder or bowel control problems that are associated with MS.
mycophenolate mofetil Off-label
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