INTRODUCTION

Multiple Sclerosis (often referred to as MS) is a disabling disease that affects Central Nervous System (CNS). It inhibits the flow of information within the brain and between brain and various body parts. The cause of MS remains unknown so far. Women are more likely to develop MS symptoms than men. There is no known cure for MS at present but treatment can help in dealing with symptoms. MS is not life-threatening.

it is an autoimmune disorder that affects the central nervous system (CNS). When a person has an autoimmune disease, the immune system attacks healthy tissue, just as it might attack a virus or bacteria.

In the case of MS, the immune system attacks the myelin sheath that surrounds and protects the nerve fibers, causing inflammation. Myelin also helps the nerves conduct electrical signals quickly and efficiently.

Multiple sclerosis means “scar tissue in multiple areas.”

When the myelin sheath disappears or sustains damage in multiple areas, it leaves a scar, or sclerosis. Doctors also call these areas plaques or lesions. They mainly affect:

As more lesions develop, nerve fibers can break or become damaged. As a result, the electrical impulses from the brain do not flow smoothly to the target nerve. This means that the body cannot carry out certain functions.

 

TYPES OF MULTIPLE SCLEROSIS

Clinically isolated syndrome (CIS)

Clinically isolated syndrome (CIS) is one of the MS disease courses. CIS refers to a first episode of neurologic symptoms that lasts at least 24 hours and is caused by inflammation or demyelination (loss of the myelin that covers the nerve cells) in the central nervous system (CNS). CIS can be either monofocal or multifocal:

The episode usually has no associated fever or infection and is followed by a complete or partial recovery. 

CIS progression to MS

Individuals who experience CIS may or may not go on to develop MS. In diagnosing CIS, the healthcare provider faces two challenges: first, to determine whether the person is experiencing a neurologic episode caused by damage in the CNS; and second, to determine the likelihood that a person experiencing this type of demyelinating event is going to go on to develop MS.

According to the 2017 revisions to the diagnostic criteria for MS, the diagnosis of MS can be made when CIS is accompanied by MRI findings (old lesions or scars) that confirm that an earlier episode of damage occurred in a different location in the CNS. The new criteria also allows for the presence of oligoclonal bands in a person's cerebrospinal fluid to help make the diagnosis. As MRI technology becomes more advanced, it is likely that the diagnosis of MS will be made more quickly and there will be fewer people diagnosed with CIS.

An accurate diagnosis at this time is important because people with a high risk of developing MS are encouraged to begin treatment with a disease-modifying therapy in order to delay or prevent a second neurologic episode and, therefore, the onset of MS. In addition, early treatment may minimize future disability caused by further inflammation and damage to nerve cells, which are sometimes silent (occurring without any noticeable symptoms). 

Relapsing-remitting MS (RRMS)

RRMS – the most common disease course – is characterized by clearly defined attacks of new or increasing neurologic symptoms. These attacks – also called relapses or exacerbations – are followed by periods of partial or complete recovery (remissions). During remissions, all symptoms may disappear, or some symptoms may continue and become permanent. However, there is no apparent progression of the disease during the periods of remission.

RRMS can be further characterized as either active (with relapses and/or evidence of new MRI activity over a specified period of time) or not active, as well as worsening (a confirmed increase in disability following a relapse) or not worsening.

Approximately 85 percent of people with MS are initially diagnosed with RRMS.

Relapsing-remitting MS is defined by inflammatory attacks on myelin (the layers of insulating membranes surrounding nerve fibers in the central nervous system (CNS)), as well as the nerve fibers themselves. During these inflammatory attacks, activated immune cells cause small, localized areas of damage which produce the symptoms of MS. Because the location of the damage is so variable, no two people have exactly the same symptoms.

Disease activity and worsening should be evaluated at regular intervals by neurologic examination and MRI. Being able to characterize the course of your disease at different points in time helps you and your MS care provider discuss your treatment options and expected outcomes. For example:

Primary progressive MS (PPMS)

PPMS is characterized by worsening neurologic function (accumulation of disability) from the onset of symptoms, without early relapses or remissions. PPMS can be further characterized as either active (with an occasional relapse and/or evidence of new MRI activity over a specified period of time) or not active, as well as with progression (evidence of disability accrual over time, with or without relapse or new MRI activity) or without progression.

Disease activity and progression can be evaluated by neurologic examination and MRI. Monitoring your disease course at different points in time helps you and your MS care provider have important conversations about your treatment options and prognosis. For example:

Secondary progressive MS (SPMS)

SPMS follows an initial relapsing-remitting course. Some people who are diagnosed with RRMS will eventually transition to a secondary progressive course in which there is a progressive worsening of neurologic function (accumulation of disability) over time. SPMS can be further characterized as either active (with relapses and/or evidence of new MRI activity during a specified period of time) or not active, as well as with progression (evidence of disability accrual over time, with or without relapses or new MRI activity) or without progression.

Disease activity and progression should be evaluated at least yearly by neurologic examination and MRI. Being able to characterize the course of your disease at different points in time helps you and your MS care provider discuss your treatment options and expected outcomes.  For example:  

SYMPTOMS

The most common symptoms of MS are:

·       Muscle weakness: People may develop weak muscles due to lack of use or stimulation due to nerve damage.

·       Numbness and tingling: A pins and needles-type sensation is one of the earliest symptoms of MS that can affect the face, body, or arms and legs.

·       Lhermitte’s sign: A person may experience a sensation like an electric shock when they move their neck, known as Lhermitte’s sign.

·       Bladder problems: A person may have difficulty emptying their bladder or need to urinate frequently or suddenly (urge incontinence). Loss of bladder control is an early sign of MS.

·       Bowel problems: Constipation can cause fecal impaction, which can lead to bowel incontinence.

·       Fatigue: This can undermine a person’s ability to function at work or at home. Fatigue is one of the most common symptoms of MS.

·       Dizziness and vertigo: These are common problems, along with balance and coordination issues.

·       Sexual dysfunction: Both males and females may lose interest in sex.

·       Spasticity and muscle spasms: This is an early sign of MS. Damaged nerve fibers in the spinal cord and brain can cause painful muscle spasms, particularly in the legs.

·       Tremor: Some people with MS may experience involuntary quivering movements.

·       Vision problems: Some people may experience double or blurred vision, a partial or total loss of vision, or red-green color distortion. This usually affects one eye at a time. Inflammation of the optic nerve can result in pain when the eye moves. Vision problems are an early sign of MS.

·       Gait and mobility changes: MS can change the way people walk, because of muscle weakness and problems with balance, dizziness, and fatigue.

·       Emotional changes and depression: Demyelination and nerve-fiber damage in the brain can trigger emotional changes.

·       Learning and memory problems: These can make it difficult to concentrate, plan, learn, prioritize, and multitask.

·       Pain: Pain is a common symptom in MS. Neuropathic pain is directly due to MS. Other types of pain occur because of weakness or stiffness of muscles.

Less common symptoms include:

·       headache

·       hearing loss

·       itching

·       respiratory or breathing problems

·       seizures

·       speech disorders

·       swallowing problems

There is also a higher risk of:

These can impact a person’s work and social life.

In the later stages, people may experience changes in perception and thinking and sensitivity to heat.

MS affects individuals differently. For some, it starts with a subtle sensation, and their symptoms do not progress for months or years. Sometimes, symptoms worsen rapidly, within weeks or months.

A few people will only have mild symptoms, and others will experience significant changes that lead to disability. However, most people will experience times when symptoms worsen and then get better.

Lhermitte’s sign is a common symptom of MS that happens when a person moves their head.

 CAUSES

The cause of MS is not known. Scientists believe MS is triggered by a combination of factors. To identify the cause, research is ongoing in areas of:

Understanding what causes MS will speed the process of finding more effective ways to treat it and — ultimately — cure it, or even prevent it from occurring in the first place.

Immunologic Factors

In MS, an abnormal immune response causes inflammation and damage in the CNS. Many different cells are involved in the abnormal immune response. Two important types of immune cells are T cells and B cells. 

Researchers continue to search for other cells and processes that could be involved in MS. Ongoing efforts to learn more about the immune-mediated process in MS — what sets it in motion, and how to slow or stop it — will bring us closer to understanding the cause of MS, better therapies and ultimately a cure.

Environmental Factors

Although the cause of MS is not known, more is being learned about environmental factors that contribute to the risk of developing MS.  There is no single risk factor that provokes MS, but several factors are believed to contribute to the overall risk.

Geographic gradient
MS is known to occur more frequently in areas that are farther from the equator. Epidemiologists — scientists who study disease patterns in large groups of people— are looking at variations in geography, demographics (age, gender and ethnic background), genetics, infectious causes and migration patterns in an effort to understand why.

Studies have shown that people born in an area with a low risk of MS who then move — or migrate — to an area with a higher risk before the age of 15 assume the risk of their new area. Such data suggest that exposure to some environmental agent before puberty may predispose a person to develop MS later on.

MS “clusters” — the perception that very high numbers of cases of MS have occurred in a specific time period or location — may provide clues to environmental or genetic risk for the disease. So far, cluster studies in MS have not produced clear evidence for the existence of any causative or triggering factor or factors in MS.

Vitamin D
Growing evidence suggests that vitamin D plays an important role in MS. Low vitamin D levels in the blood have been identified as a risk factor for the development of MS.  Some researchers believe that sun exposure (the natural source of Vitamin D) may help to explain the north-south distribution of MS. People who live closer to the equator are exposed to greater amounts of sunlight year-round. As a result, they tend to have higher levels of naturally-produced vitamin D, which is thought to support immune function and may help protect against immune-mediated diseases like MS.

Smoking
The evidence is also growing that smoking plays an important role in MS. Studies have shown that smoking increases a person’s risk of developing MS and is associated with more severe disease and more rapid disease progression. Fortunately, the evidence also suggests that stopping smoking — whether before or after the onset of MS — is associated with a slower progression of disability.

Obesity
Several studies have shown that obesity in childhood and adolescence, particularly in girls, increased the risk of later developing MS. Other studies have shown that obesity in early adulthood may also contribute to an increased risk of developing MS.  Also, obesity may contribute to inflammation and more MS activity in those already diagnosed with MS.

Infectious Factors

Many viruses and bacteria — including measles, canine distemper, human herpes virus-6, Epstein-Barr virus (EBV), and Chlamydia pneumonia — have been or are being investigated to determine if they are involved in the development of MS.  EBV, the virus that causes mononucleosis, has received significant attention in recent years. A growing number of research findings indicate that previous infection with EBV contributes to the risk of developing MS.

Genetic Factors

MS is not an inherited disease, meaning it is not a disease that is passed down from generation to generation.  However, in MS there is genetic risk that may be inherited. In the general population, the risk of developing MS is about 1 in 750 - 1000. In identical twins, if one twin has MS the risk that the other twin will develop MS is about 1 in 4. The risk of developing MS is also increased when other first degree relative (parents, siblings and children) have MS, but far less than in identical twins.

About 200 genes have been identified that each contribute a small amount to the overall risk of developing MS. Research is ongoing to better understand genetic risk and other factors that contribute to the development of MS.

RISK FACTORS

These factors may increase your risk of developing multiple sclerosis:

·         Age. MS can occur at any age, but onset usually occurs around 20 and 40 years of age. However, younger and older people can be affected.

·         Sex. Women are more than two to three times as likely as men are to have relapsing-remitting MS.

·         Family history. If one of your parents or siblings has had MS, you are at higher risk of developing the disease.

·         Certain infections. A variety of viruses have been linked to MS, including Epstein-Barr, the virus that causes infectious mononucleosis.

·         Race. White people, particularly those of Northern European descent, are at highest risk of developing MS. People of Asian, African or Native American descent have the lowest risk.

·         Climate. MS is far more common in countries with temperate climates, including Canada, the northern United States, New Zealand, southeastern Australia and Europe.

·         Vitamin D. Having low levels of vitamin D and low exposure to sunlight is associated with a greater risk of MS.

·         Certain autoimmune diseases. You have a slightly higher risk of developing MS if you have other autoimmune disorders such as thyroid disease, pernicious anemia, psoriasis, type 1 diabetes or inflammatory bowel disease.

·         Smoking. Smokers who experience an initial event of symptoms that may signal MS are more likely than nonsmokers to develop a second event that confirms relapsing-remitting MS.

DIAGNOSIS

There are no specific tests for MS. Instead, a diagnosis of multiple sclerosis often relies on ruling out other conditions that might produce similar signs and symptoms, known as a differential diagnosis.

Your doctor is likely to start with a thorough medical history and examination.

Your doctor may then recommend:

·         Blood tests, to help rule out other diseases with symptoms similar to MS. Tests to check for specific biomarkers associated with MS are currently under development and may also aid in diagnosing the disease.

·         Spinal tap (lumbar puncture), in which a small sample of cerebrospinal fluid is removed from your spinal canal for laboratory analysis. This sample can show abnormalities in antibodies that are associated with MS. A spinal tap can also help rule out infections and other conditions with symptoms similar to MS.

·         MRI, which can reveal areas of MS (lesions) on your brain and spinal cord. You may receive an intravenous injection of a contrast material to highlight lesions that indicate your disease is in an active phase.

·         Evoked potential tests, which record the electrical signals produced by your nervous system in response to stimuli. An evoked potential test may use visual stimuli or electrical stimuli. In these tests, you watch a moving visual pattern, or short electrical impulses are applied to nerves in your legs or arms. Electrodes measure how quickly the information travels down your nerve pathways.

In most people with relapsing-remitting MS, the diagnosis is fairly straightforward and based on a pattern of symptoms consistent with the disease and confirmed by brain imaging scans, such as MRI.

Diagnosing MS can be more difficult in people with unusual symptoms or progressive disease. In these cases, further testing with spinal fluid analysis, evoked potentials and additional imaging may be needed.

TREATMENT

There is no cure for MS, but treatment is available that can:

Some people also use complementary and alternative therapies, but research does not always confirm the usefulness of these.

Medications to slow progression

Several disease-modifying therapies (DMTs) have approval from the Food and Drug Administration (FDA) for the relapsing forms of MS. These work by changing the way the immune system functions.

A doctor may give some of these by mouth, some by injection, and some as an infusion. How often the person needs to take them and whether or not they can do this at home will depend on the drug.

The following DMTs currently have approval:

Injectable medications

Oral medications

Infused medications

Current guidelines recommend using these drugs from the early stages, as there is a good chance that they can slow the progression of MS, especially if the person takes them when symptoms are not yet severe.

Some drugs are more useful at specific stages. For example, a doctor may prescribe mitoxantrone at a later, more severe stage of MS.

A doctor will monitor how well a drug is working, as there may be adverse effects, and the same drugs do not suit everyone. New drug options coming onto the market are proving to be safer and more effective than some existing ones.

Adverse effects of immunosuppressant drugs include a higher risk of infections. Some medications may also harm the liver.

If a person notices adverse effects or if their symptoms get worse, they should seek medical advice.

Medications for relieving symptoms during a flare

Other drugs are useful when a person experiences a worsening of symptoms, during a flare. They will not need these drugs all the time.

Corticosteroids: These reduce inflammation and suppress the immune system. They can treat an acute flare-up of symptoms in certain types of MS. Examples include Solu-Medrol (methylprednisolone) and Deltasone (prednisone). Steroids can have adverse effects if a person uses them too often, and they are not likely to provide any long-term benefit.

Behavioral changes: If vision problems occur, a doctor may recommend resting the eyes from time to time or limiting screen time. A person with MS may need to learn to rest when fatigue sets in and to pace themselves so they can complete activities.

Problems with mobility and balance: Physical therapy and walking devices, such as a cane, may help. The drug dalfampridine (Ampyra) may also prove useful.

Tremor: A person may use assistive devices or attach weights to the limbs to reduce shaking. Medications may also help with tremors.

Fatigue: Getting enough rest and avoiding heat can help. Physical and occupational therapy can help teach people more comfortable ways to do things. Assistive devices, such as a mobility scooter, can help conserve energy. Medication or counseling may help boost energy by improving sleep.

Pain: A doctor may prescribe anticonvulsant or antispasmodic drugs or alcohol injections to relieve trigeminal neuralgia, a sharp pain that affects the face. Pain relief medication, such as gabapentin, may help with body pain. There are also medications to relieve muscle pain and cramping in MS.

Bladder and bowel problems: Some medications and dietary changes can help resolve these.

Depression: A doctor may prescribe a selective serotonin reuptake inhibitor (SSRI), as these are less likely to cause fatigue than other antidepressant drugs.

Cognitive changes: Donepezil, a drug for Alzheimer’s, may help some people.

Complementary and alternative therapies

The following may help with different aspects of MS:

Medical marijuana

Studies have suggested that cannabis may help relieve pain, muscle stiffness, and insomnia. However, there is not enough evidence to confirm this.

People should also note that:

A person should ask their doctor for advice before using cannabis, as some forms can have adverse effects. Smoking cannabis is unlikely to be beneficial, and it may make symptoms worse.

Rehabilitation and physical therapy

Rehabilitation can help improve or maintain a person’s ability to perform effectively at home and work.

Programs generally include:

Physical therapy: This aims to provide the skills to maintain and restore maximum movement and functional ability.

Occupational therapy: The therapeutic use of work, self-care, and play may help maintain mental and physical function.

Speech and swallowing therapy: A speech and language therapist will carry out specialized training for those who need it.

Cognitive rehabilitation: This helps people manage specific problems in thinking and perception.

Vocational rehabilitation: This helps a person whose life has changed with MS to make career plans, learn job skills, get and keep a job.

Plasma exchange

Plasma exchange involves withdrawing blood from the individual, removing the plasma, replacing it with new plasma, and transfusing it back into the person.

This process removes the antibodies in the blood that are attacking parts of the person’s body, but whether it can help people with MS is unclear. Studies have produced mixed results.

Plasma exchange is usually only suitable for severe MS attacks.

Stem cell therapy

Scientists are looking into the use of stem cell therapy to regenerate various body cells and restore function to those who have lost it due to a health condition.

Researchers hope that one day, stem cell therapy techniques may be able to reverse the damage done by MS and restore functionality in the nervous system.