‘Sclerosis’ is a Greek word, referring to the scarring that damages the nerves. ‘Multiple’ refers to the many parts of the body that can be affected.
Multiple Sclerosis (MS) is a condition that affects the brain and spinal cord (known as the central nervous system or CNS).
It causes damage to the nerves of the CNS, as the body’s immune system attacks the protective covering of nerve fibers, which then affects the way the messages flow within the brain, and from the brain to the rest of your body.
Multiple Sclerosis (MS) is a condition that affects the brain and spinal cord. The body’s immune system attacks the protective covering of nerve fibers, which then affects the way the electrical messages flow within the brain, and from the brain to the rest of your body. It causes damage to the nerves, which causes scarring. In fact, ‘Sclerosis’ is a Greek word, referring to the scarring of the nerves. ‘Multiple’ refers to the many parts of the brain and spinal cord that can be affected.
The symptoms of MS vary depending on the degree of nerve damage and which nerves are affected. Some people may only have mild symptoms that come and go over time, while others may gradually notice problems with walking.
MS as disease has been known for centuries and for most of that time there were no effective treatments. However, in the last 20 years, very effective drugs that can change the course of the disease, known as disease modifying therapy (DMT), have become available. There is still no ‘cure’ for MS, and its cause is only partly understood.
It is impossible to understand MS without first understanding a little about how the human nervous system and immune system normally work.
The nervous system has a central part and a peripheral part. The central part consists of the brain, spinal cord, and optic nerves. The peripheral part lies outside of this, and includes the nerves that lead from the spinal cord into the muscles, and the nerves that bring back sensation from the skin into the spinal cord.
The main cells in the nervous system are called neurons. The body of the neurons lie in the brain, and send a long nerve fiber stretching all the way into the spinal cord. This is called an axon. The axon is covered by a fatty, insulating substance called myelin.
Most parts of the brain have their own unique function. For example, when you want to move your right foot, the body of neurons in the motor cortex of the left side of the brain are stimulated. An electrical signal spreads down the axon, all the way down to the spinal cord. The signal is relayed to another neuron whose axon exits the spinal cord. These axons combine together to make a nerve, which signals the muscle and makes it move.
Similarly when you step on something sharp, nerve endings from the skin of your foot send electrical signals through the nerves to the spinal cord, and to the sensory area of the brain.
Nerves conduct electricity and all electrical systems require insulation to avoid short circuiting and for effective transmission of a current. Myelin is the insulation around the nerves that does this job.
The immune system is the defense system of the body. It is meant to protect us from things like infection and cancer. The main ‘soldiers’ of the immune system are the white blood cells. Of the many kinds of white blood cells, the two primarily involved in causing autoimmune diseases are the T and B cells. These are the cells that release many different substances that cause inflammation.
Inflammation is the word used to describe the process and damage that the immune system causes in areas that it considers ‘foreign’. In an inflamed area, white blood cells accumulate and release substances that cause damage.
In an autoimmune disease, the body’s defense system mistakes the components of our own organs as foreign, causing inflammation. Virtually any organ in the body can be affected by an autoimmune disease. Examples include the joints (rheumatoid arthritis), thyroid-hypothyroidism, ulcerative colitis and Crohn’s disease, skin-vitiligo, and psoriasis. The mechanisms of inflammation are surprisingly similar in many autoimmune diseases and therefore the medicines used to treat them are often similar. Only the substance that triggers the immune system varies. The tendency for autoimmunity can lead to more than one autoimmune disease being present in the same person. Because there are genetic factors involved in autoimmune diseases, they can occur in more than one person in the same family.
MS is the most common autoimmune disease that affects the central nervous system, affecting the brain, optic nerves, and spinal cord. We are not sure which substances in the central nervous system trigger the immune response, but myelin, the protein covering the nerves, is definitely one.
We still don’t know for certain what causes MS. Experts believe that there may be a combination of factors that make MS more likely to develop, rather than a single cause. These risk factors are things that we are all exposed to every day, but only a small number of people will go on to develop MS. Doctors aren’t able to predict who will and won’t get the disease.
It is widely believed that MS is an autoimmune disease. This means that our body’s own immune system, which is responsible for fighting infection, starts to attack healthy cells in a faulty immune response. When someone has MS, the immune system targets something called ‘myelin’, a fatty protein that covers the nerves in our brain and spinal cord. This is called demyelination. When this happens, our nerves can’t conduct electrical impulses properly. The messages from the brain can’t travel along the nerves smoothly, causing a delay or complete interruption.
In the early stages of MS, the body can repair this damage to some degree, and replace the myelin so messages can still travel along the nerves. This is called remyelination. The brain can also reroute messages. Over time though, the loss of myelin leaves nerves exposed and more at-risk of permanent damage.
MS is not an inherited condition, which means that it is not hereditary or passed on from other family members. However, some people may have specific genes that make them more likely to develop the disease, so there is a genetic risk that it might be inherited. For example, in identical twins, if one has MS, then there is a much higher chance that the other will develop it too. While several members of the same family may have MS, having the specific genes does not increase risk of other family members having the condition and other risk factors are needed to trigger the onset.
Research has shown that while an infection does not cause MS, it can act as a trigger, which sets off a number of events within the body which may develop into MS over a long period of time. We still don’t know which viruses can cause this trigger, or the exact chain of events that lead to MS, but scientists are exploring the link with Epstein-Barr virus (EBV), measles, and human herpes virus-6.
Studies have revealed that there may be several environmental factors that increase the chance of MS developing. These include:
While doctors can’t predict who will get MS, they have found that there are certain patterns in the distribution of the disease that might help us understand what causes it. This is called epidemiology. Factors affecting epidemiology include:
The number of people being diagnosed with MS is increasing and experts aren’t sure why. While it may be down to increased awareness of the disease and more sophisticated diagnostic techniques, there may be other factors involved that are not yet clear.
Areas of inflammation caused by white blood cells appear as white spots on the brain and spinal cord. If the spots are in areas that perform a very obvious function, then even the slightest damage will cause noticeable symptoms. For example, if the nerves to the eye become even slightly inflamed, a reduction in vision will be noticed. Similarly, if inflammation in the spinal cord occurs in the nerves that carry pain, it will immediately be felt. However, if the inflammation is in the areas that process memory or judgment, or in the fibers that link-up to such important areas, it may go totally unnoticed.
Inflammation and demyelination usually develop over hours or days (it does not occur abruptly like a stroke). It usually then persists for several days or weeks, and then subsides and recovers. The recovery happens because the immune system decides to stop attacking the nerves. The nervous system then starts repairing itself, known as ‘remyelination’, and function may return to normal.
An episode of new inflammation is called a ‘relapse’ or ‘attack’. Symptoms of a relapse depend on the area that is inflamed and there can be many. They vary from person to person, and are hard to predict. They may come and go, and can affect different people at different times. Some symptoms are responsive to treatment while others are more difficult to manage. As MS affects the nerves of the brain and spinal cord, it can affect almost any part of the body and its functions.
We will now look at common symptoms of MS. Whilst most people won’t experience all of them, it is important to recognize the signs to ensure an accurate diagnosis as soon as possible, and to rule out other possible medical complications.
Since MS affects any part of the brain or spinal cord, lots of other symptoms are possible, but are usually less common. These include trigeminal neuralgia (an electric shock-like pain in the face), seizures, and problems with speech, swallowing, breathing, and hearing.
The presence of spots on the brain or spinal cord that are typical for MS are present, but the individual has no symptoms that are relevant to the spots. Common examples include patients who have an MRI scan for headaches (MS does not cause headaches), and white spots that are typical for MS are seen. There is risk of development of symptoms in future. Many cases of RIS are observed without treatment but in some patients, disease modifying treatment is advised.
This refers to the first episode of symptoms caused by inflammation in the CNS. If an MRI then reveals spots within the brain that are typical for MS, it is called CIS. If further new spots develop or new symptoms occur, a diagnosis of RRMS (see below) is made. Some cases of CIS are observed, while most cases move onto some form of treatment.
This is the most common form of MS, affecting around 85% of people initially diagnosed with the disease. It follows a course of flare ups, where new symptoms develop or existing symptoms worsen (known as a relapse or attack), followed by a period called remission, where symptoms improve, or return to baseline.
Relapses usually last for days or weeks and can be mild or severe. It is impossible to predict when and how often they will happen. Typically, in patients not on disease modifying treatment, relapses may occur a couple of times a year but some patients go years without relapses.
It is important to understand that inflammation or damage in many parts of the brain will not cause any external symptoms. Patients notice symptoms only when certain parts of the nervous system are affected. For example, if the optic nerve that connects the eye to the brain is inflamed, it may cause eye pain and blurry vision and we will notice it straight away. But if the area of the brain that deals with memory or judgment is affected, we may not notice it. Similarly, a little unsteadiness due to inflammation in the balance organ (cerebellum) being affected may be ignored, while a burning pain in the leg due to formation of the nerves in the spinal cord that usually carry pain sensation, will make you seek medical attention. MRI scans which reveal this asymptomatic inflammation are therefore an important tool in the management of MS to assess the severity and effectiveness of treatments.
Most of the disease modifying drugs available to treat MS work on the relapsing remitting stage of MS.
SPMS usually follows an RRMS course, hence it is called a secondary phase. Over time, MS changes so that fewer relapses are experienced, but the level of disability increases. Sometimes, people are already at this stage when they receive their diagnosis. Progression to this stage is different for everyone – for some it happens quickly, whilst for others it can take a long time. For reasons that are not yet clear, the medications that we use in relapsing remitting MS are not that effective in secondary progressive MS.
In this type of MS, symptoms are noticed very gradually, and they continue to progress without any clear relapses. Some scientists believe that PPMS may be simply SPMS, where the relapsing remitting stage was not symptomatic. Some others feel that the mechanisms underlying PPMS are different from RRMS. Treatments are usually not that effective, but are most beneficial in patients where new areas of inflammation keep appearing on MRI scans.
You may also come across the following terms:
A relapse refers to new symptoms or signs, caused by new inflammation. It always lasts more than 24 hours. It may need treatment with steroids to hasten recovery, and sometimes a change in the disease modifying treatments that are being taken.
A pseudo-relapse is not caused by new inflammation. It is only a temporary reduction in function which is likely due to changes in the flow of electric currents through the nerves. This can happen when the body heats up, for example after exercise. Sometimes other infections such as a urinary tract infection, or taking new medications can trigger it. It can also occur during physiological changes like menstruation. Rest and managing the underlying problem usually resolves it.
Sometimes the diagnosis of MS is straightforward. Sometimes, it can take a long time while other neurological conditions are ruled out.
Unfortunately, there is no specific single diagnostic test for MS, so there are a set of criteria that doctors look for to confirm a diagnosis. These include:
These criteria assume that MS is the most common cause of relapsing neurological problems that affects multiple areas of the brain or spinal cord, with abnormal MRI scans in people at risk. Depending on geography, ethnicity and family history, other diagnoses need to be considered and other tests may be needed.
Once MS is suspected, a doctor will then use the following tools to confirm a diagnosis:
While there is no cure for MS, many types of treatment are available that can slow or prevent attacks from occurring, and delay or hopefully stop progression of the disease. Treatment can also help to manage symptoms and speed-up recovery following a relapse.
Treatment for MS typically involves medication therapy, which can be divided into two main types:
When a new symptom develops, which is significant and disabling (and if this is confirmed as a relapse due to new inflammation), corticosteroid (cortisone) is given intravenously for 5 -7 days. Steroids can only be given for a short duration, as long-term use may cause side effects.
Occasionally steroids alone are insufficient and a plasma exchange-procedure is given, where the blood is cleaned of inflammatory substances, like a dialysis.
These are medications that treat the disease itself. There are about 15 types of such medication. Depending on the individual’s specific diagnosis, caregivers offer the latest approved therapies to patients, which may be given as tablets, injections, or infusion (intravenous) medications. Infusion therapies, which can slow down the development of MS and reduce the number of flare-ups, are delivered on an outpatient basis at the Cleveland Clinic Abu Dhabi Infusion Center.
Natalizumab is given intravenously as an infusion in the hospital once a month, to reduce the number and severity of relapses.
It acts by preventing white blood cells from passing from the blood into the central nervous system where they can attack and cause damage to the nerves. It reduces inflammation by 80%.
While treatment with natalizumab is beneficial, there are possible side effects. Patients with the JC Virus are not recommended to take the medication as the risk of developing an illness called progressive multifocal leukoencephalopathy (PML) is increased. This is a rare but fatal brain infection. When your immune system is weakened and your body is less able to fight infections, the JC virus can become active and cause inflammation and damage to the brain. A routine blood test is done to detect the JC virus and provide an indication of the risk that you might develop PML.
There is also an increased risk of developing infections, and a risk of liver damage when taking natalizumab. Routine blood tests are done to monitor these levels. Commonly reported side effects of natalizumab include dizziness, nausea, urticaria (a skin rash) and stiffness.
Ocrelizumab is given intravenously as an infusion in the hospital. The first dose is given as two separate infusions, two weeks apart. Then the medication is given once every 6 months. This medication is given to treat active relapsing remitting, and very active relapsing remitting MS. Ocrelizumab acts by killing B cells, which are a type of white blood cell (lymphocyte). These cells are involved when the immune system attacks nerve cells. The targeted B cells are then destroyed.
The possible side effects associated with ocrelizumab include, but not limited to, flu-like symptoms, weakness, muscle aches, tiredness, dizziness, headaches, allergic reactions, breathlessness, painful mouth sores, ulcers, blisters on skin, abnormal blood counts causing anemia, and bleeding. There is a small risk of progressive multifocal leukoencephalopathy (PML) which is a rare but fatal viral brain infection. Routine blood tests are completed while taking ocrelizumab.
Alemtuzumab is given intravenously as an infusion in the hospital in two treatment courses, twelve months apart. It is given to treat very active relapsing remitting MS and reduces the number of relapses by over two thirds (70%). Alemtuzumab is a monoclonal antibody that targets and kills immune cells. It binds to a marker, CD52, on the lymphocytes or white blood cells, and kills them.
You cannot take this treatment if you have an immune deficiency, including HIV, suffer from allergic reactions, or if you are pregnant. There is a risk of hypothyroidism, bleeding, and a risk of serious infections. Monthly blood and urine checks will be performed due to the serious nature of the side effects, as well as checks every 3 months for thyroid function, and annual cervical smear tests. Patients should not receive any live vaccines for the rest of their life as it reduces the body’s ability to develop immunity. More recently there has been concern that this drug may increase the risk of strokes.
For further information:
Lemtrada (alemtuzumab) | MS Trust
Lemtrada | National Multiple Sclerosis Society (nationalmssociety.org)
Lemtrada (alemtuzumab) Fact Sheet | Cleveland Clinic
Rituximab is given intravenously as an infusion in the hospital. This medication depletes the B-white blood cells.
Common side effects associated with rituximab include flu-like symptoms, weakness, muscle aches, tiredness, dizziness, headaches, allergic reactions, breathlessness, painful mouth sores, ulcers, blisters on skin, abnormal blood counts causing anemia, bleeding, risk of serious infections, and death. There is a small risk of progressive multifocal leukoencephalopathy (PML) which is a rare but fatal viral brain infection. Routine blood tests are completed while taking rituximab to monitor your condition carefully.
For more information:
Rituximab injection (clevelandclinic.org)
Ofatumumab is a self-administered subcutaneous injection that comes in pre-filled syringes. It is given for the treatment of relapsing remitting MS. Ofatumumab works by attacking specific targets in the immune system. It binds to a marker on the surface of B lymphocytes and destroys them, so that they cannot attack nerve cells.
Common side effects are injection-related reactions. Other side effects that affect at least 10% of people taking ofatumumab, include head colds, headache, chest infections, and urinary tract infections. Routine blood tests are given to people taking this medication to monitor for any side effects.
For more information:
Ofatumumab | MS Trust
Kesimpta | National Multiple Sclerosis Society (nationalmssociety.org)
Interferon beta 1a is a self-administered subcutaneous injection that comes in pre-filled syringes, and is for relapsing remitting MS. It is given once every three weeks. It can also reduce the number of brain lesions on MRI and reduce the risk of worsening disability.
Interferon beta 1a works by reducing both inflammation and the immune response that is attacking the body’s own nerve cells. Routine blood monitoring is given to anyone taking this medication. Common side effects include flu-like symptoms and myalgia (muscle pain), but these are transient and should improve spontaneously in most people. Prophylactic paracetamol or ibuprofen (unless contraindicated) can be used to relieve these side effects. Injection site reactions can occur, but alternating injection sites will reduce this.
For more information:
Rebif (interferon beta 1a) | MS Trust
Rebif | National Multiple Sclerosis Society (nationalmssociety.org)
Peginterferon beta 1a is a self-administered subcutaneous injection that comes in pre-filled syringes, given once every two weeks. It is used to treat relapsing remitting MS. Peginterferon beta 1a works by reducing both inflammation and the immune response that is attacking the body’s nerve cells. Routine blood monitoring is offered to anyone taking this medication. Common side effects include flu-like symptoms and myalgia (muscle pain), but these are transient and should improve spontaneously in most people. Prophylactic paracetamol or ibuprofen can be used to relieve these side effects. Injection site reactions can occur, but alternating injection sites will reduce this.
For more information:
Plegridy (peginterferon beta 1a) | MS Trust
Plegridy | National Multiple Sclerosis Society (nationalmssociety.org)
Interferon beta 1a is a self-administered subcutaneous injection given once a week. It is given to treat relapsing remitting MS. Interferon beta 1a works by reducing inflammation and the immune response that is attacking the body. Common side effects include flu-like symptoms and myalgia (muscle pain), but these are transient and should improve spontaneously in most people. Prophylactic paracetamol or ibuprofen can be used to relieve these side effects. Injection site reactions can occur, but alternating injection sites will reduce this.
For more information:
Avonex (interferon beta 1a) | MS Trust
Avonex | National Multiple Sclerosis Society (nationalmssociety.org)
Glatiramer acetate is a once a day, self-administered subcutaneous injection that comes in pre-filled syringes. It is given to treat relapsing remitting MS. Glatiramer acetate works by diverting an immune attack away from the myelin on nerve cells. Routine blood monitoring is given. Common side effects include flu-like symptoms and myalgia (muscle pain), but these are transient and should improve spontaneously in most people. Prophylactic paracetamol or ibuprofen can be used to relieve these side effects. Injection site reactions can occur, but alternating injection sites will reduce this.
For more information:
Copaxone (glatiramer acetate) | MS Trust
Copaxone | National Multiple Sclerosis Society (nationalmssociety.org)
Fingolimod is a tablet taken once a day for relapsing remitting MS. Fingolimod acts by binding to certain white blood cells (lymphocytes), so they become trapped in the lymph nodes. This prevents them from crossing into the central nervous system (CNS), which helps to reduce inflammation and stops them from damaging nerve cells.
Common side effects include an increased risk of infections, cough, headache, back pain, and diarrhea. Contra-indications to using this medication are immunosuppression, active infection, and active malignancies (except cutaneous basal cell carcinoma).
Fingolimod can slow the heart rate after the first dose, so it is to be avoided in those with cardiovascular problems. An ECG test is completed prior to starting on Fingolimod. Progressive multifocal leukoencephalopathy (PML), an uncommon and serious brain viral infection, has been described in a handful of cases. Less common side-effects include the risk of macular oedema, so an eye examination will be completed before starting treatment. Liver enzymes can increase, and white blood counts can drop, so levels will be monitored every 3 months.
For more information:
Gilenya (fingolimod) | MS Trust
Gilenya | National Multiple Sclerosis Society (nationalmssociety.org)
Fingolimod oral capsules (clevelandclinic.org)
Dimethyl fumarate is a tablet taken twice daily to treat relapsing remitting MS. Dimethyl fumarate works by reducing the inflammation in an immune response and protects nerve cells from damage. Common side effects include flushing, diarrhea, nausea, abdominal pain, and headache. Taking dimethyl fumarate with food may reduce the incidence of flushing.
White blood cell counts can fall, so need to be monitored every 3 months. There is a small risk of progressive multifocal leukoencephalopathy (PML), which is a rare but fatal viral brain infection.
For more information:
Tecfidera (dimethyl fumarate) | MS Trust
Tecfidera | National Multiple Sclerosis Society (nationalmssociety.org)
Use of DMF in Multiple Sclerosis (Tecfidera, BG-12) Fact Sheet | Cleveland Clinic
Cladribine is taken as a tablet for very active relapsing remitting MS. It is taken in two treatment courses, twelve months apart. Cladribine works by slowly reducing the numbers of T and B lymphocytes (white blood cells that cause the damage associated with MS). Side effects can include a reduced white blood cell count (lymphopenia) and herpes (oral herpes and shingles). Prior to starting treatment with cladribine, baseline blood tests are done and then repeated every 3 months.
For more information:
Mavenclad (cladribine) | MS Trust
Mavenclad | National Multiple Sclerosis Society (nationalmssociety.org)
Oral Cladribine (Mavenclad®) for MS | Mellen Center Approach | Cleveland Clinic
Siponimod is a tablet given to treat secondary progressive MS. It is taken once a day. It also reduces the frequency of relapse. Siponimod works by binding to and trapping the lymphocytes (white blood cells) in the lymph glands. This reduces the number of lymphocytes in the blood from reaching the brain, and therefore reducing attacks on nerve cells in the brain and spinal cord.
The side effects of siponimod include low white blood cell count, increased liver enzyme levels, slower heart rate when starting treatment, macular oedema (swelling in the back of the eye affecting vision), high blood pressure, shingles, and convulsions. An ECG test along with an eye exam will be completed prior to starting on siponimod. As liver enzymes can rise and white blood counts can drop, your levels will be monitored every 3 months.
For more information:
Siponimod | MS Trust
Mayzent | National Multiple Sclerosis Society (nationalmssociety.org)
Siponimod | MS Approaches | Cleveland Clinic
Teriflunomide is a tablet taken to treat relapsing remitting MS. It is taken once a day . Teriflunomide works by reducing the number of white blood cells (B-cells and T-cells) that cause damage to nerve cells seen in MS. Common side effects include feeling sick, diarrhoea, and hair thinning, which can occur during the first few months of treatment but generally later improve. Increased blood levels of liver enzymes can also occur, so levels will be monitored every 3 months.
For more information:
Aubagio (teriflunomide) | MS Trust
Aubagio | National Multiple Sclerosis Society (nationalmssociety.org)
This includes a range of medications used to manage symptoms of MS, including pain, spasticity (muscle stiffness), urinary urgency or frequency, muscle spasms, and fatigue. Various options, including botox injections, may be offered.
MS is a complex condition and treatment is a long-term process that lasts the course of the disease. Having access to comprehensive, multidisciplinary care is key to treating MS and improving quality of life. The Multiple Sclerosis Program at Cleveland Clinic Abu Dhabi provides a team of specialists who work together to help you manage the disease and its symptoms. Each team member provides unique insights into ways to modify the course of the disease, deal with relapses, treat the symptoms, and address other factors such as emotional wellbeing.
These include a neuro rehabilitation physician, physiotherapist, occupational therapist, nutritionist, psychologist, gastroenterologist, speech and swallow therapists, and many other professionals.
Some patients have incomplete recovery from attacks or develop progressive difficulties that will need help from physical therapists or occupational therapists. Neuro rehabilitation consultants can supervise and assist with more complex neuro-rehabilitation needs.
Patients are offered a tailored treatment plan, which can include physiotherapy, occupational therapy, and rehabilitation, that helps improve or maintain functions effectively. They also focus on overall fitness and address things such as mobility.
Addressing emotional health is an important part of comprehensive care. Everyone copes with various life stressors in different ways, and while some may deal with it very well without any help from professionals, some may find it extremely difficult. It can therefore be helpful to meet with a psychologist to develop coping strategies, and who can also provide nonmedical treatments for depression and anxiety. Occasionally, patients develop other cognitive issues associated with MS. A psychologist can support with this.