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Multiple sclerosis Causes, Symptoms and Treatment

Multiple sclerosis is the inflammatory disease that attacks the central nervous system. The disease worsens slowly in most cases and depends, among other things, on the severity of signs and symptoms and the frequency of relapses.

The MS is a disease that affects the central nervous system , particularly the brain, optic nerves and the spinal cord. It impairs the transmission of nerve impulses and can be manifested by very variable symptoms  : numbness of a limb, visual disturbances, sensations of electric discharge in a limb or in the back, movement disorders, etc.

Most often, multiple sclerosis develops with relapses , during which symptoms reappear or new symptoms occur. After a few years, relapses leave sequelae (permanent symptoms) that can become very disabling . The disease can affect many functions: movement control, sensory perception, memory, speech, etc.

The Multiple Sclerosis is a disease autoimmune chronic, whose severity and progression are highly variable. It was first described in 1868 by the French neurologist Jean Martin Charcot.

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The disease is characterized by inflammation reactions that in some places cause the destruction of myelin (demyelination). Myelin is a sheath that surrounds the nerve fibers (see diagram). Its role is to protect these fibers and accelerate the transmission of messages or nerve impulses. The immune system of those affected would destroy myelin by considering it as foreign to the body (autoimmune reaction). Thus, in some parts of the nervous system, the impulses are slower or completely blocked, which causes the different symptoms. Apart from relapses, the inflammation disappears and myelin partially re-forms around the fibers, resulting in complete or partial regression of symptoms. However, in cases of repeated and prolonged demyelination, neurons can be permanently destroyed. This then causes a permanent disability.

The parts of the nervous system affected by the disease resemble plaques that can be visualized during magnetic resonance imaging (MRI) , hence the term multiple sclerosis .

Prevalence

It is estimated that, on average, 1 in 1,000 people have multiple sclerosis, but this prevalence varies from country to country. The northern countries are more affected than countries near the equator. In Canada , the rate is thought to be among the highest in the world (1/500), making it the most common chronic neurological disease in young adults. It is estimated that about 100,000 French suffer from it, while Canada has the highest rate of multiple sclerosis in the world with an equivalent number of cases. Still unexplained, there are 2 more womenthan men with multiple sclerosis. The disease is most often diagnosed in people aged 20 to 40, but it can also, in rare cases, affect children (less than 5% of cases).

Causes of Multiple sclerosis

The MS is a complex disease that appears inexplicably. Researchers believe that it occurs in the presence of a combination of environmental factors in people whose inheritance predisposes them to the disease (see sections at Risk and Risk Factors ). A viral infection contracted during childhood , such as the measles virus or the Epstein-Barr virus or mononucleosis could be involved. As for genetic factors predisposing, many also. Several potentially involved genes have been identified in recent years and could increase the risk of multiple sclerosis.

Diagnostic of Multiple sclerosis

There is no test that can definitively diagnose multiple sclerosis . In fact, diagnostic errors are common, as many diseases can manifest as MS-like symptoms.

In general, the diagnosis is based on:

  • Medical history, with a medical questionnaire that establishes the history of problems related to the disorder and identifies, if any, previous neurological manifestations.
  • A physical examination that consists of assessing vision, muscle strength, muscle tone, reflexes, coordination, sensory functions, balance and ability to move.
  • A lumbar puncture which consists of collecting cephalo-rachidian fluid (CSF) in the lumbar region. This process allows us to test whether the CSF – which circulates around the brain and the spinal cord – shows an increase in some proteins and contains molecules that demonstrate abnormal production of antibodies.
  • A recording of electrical activity that measures the time it takes visual information to get to the brain.
  • Magnetic resonance imaging allows visualization of the lesions in the white matter (which contains myelina) of the brain, cerebellum and spinal cord.
The multiple sclerosis is difficult to diagnose and it usually takes 2 to have suffered relapses or more, with at least a partial remission, to confirm the diagnosis.

In order to establish a definitive diagnosis of multiple sclerosis, the neurologist must be convinced that myel’line is affected in two different places that cannot be the consequence of other diseases. (Spatial criterion). In addition, he must also show that these attacks occurred at two different times (time criterion). The medical questionnaire is therefore crucial for a thorough knowledge of the symptoms and for checking whether there have been neurological manifestations in the past.

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Evolution

The evolution of multiple sclerosis is unpredictable . Each case is unique. Neither the number of relapses, nor the type of attack, nor the age of the diagnosis can predict or envisage the future of the person who has it. There are benign forms that do not cause any physical difficulty, even after 10 years or 20 years of illness. Other forms can evolve rapidly and be more disabling . Finally, some people have only one thrust in their entire life. It should be known that the life expectancy of people with is reduced from 7 to 14 years, according to a large study. Half of the deaths are related to the complication of sclerosis. The mortality rate for infectious and respiratory diseases, suicide and cardiovascular disease is higher in people with multiple sclerosis compared to the general population.

Forms of the disease

In general, there are 3 main forms of multiple sclerosis, depending on how the disease evolves over time.

  • Remittent form. In 85% to 90% of cases, the disease begins with the relapsing-remitting form (also called “relapsing-remitting”), characterized by relapsing episodes of remissions . A thrust is defined as a period of new neurological signs or recurrence of old symptoms lasting at least 24 hours, separated from the previous thrust by at least 1 month. In general, outbreaks last from a few days to 1 month, and then gradually disappear. In the majority of cases, after several years, this form of the disease can evolve into a secondarily progressive form.
  • Primary progressive form (or progressive from the start). This form is characterized by a slow and constant evolution of the disease, from the diagnosis. It concerns 10% of cases. Unlike the remittent form, there are no real outbreaks, although the disease may get worse at times. This form usually appears later in life, around the age of 40.
  • Secondarily progressive form . After an initial remitting form, the disease can worsen continuously. This is called secondarily progressive form. Flare-ups can occur, but they are not followed by frank remissions and the handicap gets worse gradually. Most people with relapsing-remitting will develop a progressive form within 15 years of being diagnosed with the disease.
  • Isolated clinical syndrome. It is a first episode characteristic of the disease (eg, optic neuritis, symptom related to brainstem involvement, myelitis) and has the characteristics of a demyelination of inflammatory origin but which does not satisfy all diagnostic criteria for multiple sclerosis. Symptoms of the isolated clinical syndrome vary from one person to another, as they depend on the localization of the lesions in the central nervous system. It is estimated that one in five people will develop multiple sclerosis after 10 years when the isolated clinical syndrome is not accompanied by the typical lesions of multiple sclerosis.

The symptoms of multiple sclerosis

The symptoms depend on the location of the plaques, that is, the part of the nervous system that is affected by the inflammation. They are very variable from one person to another, as well as from one push to another. In the majority of cases, the disease begins with a single symptom. Here are the main ones.

  • Visual disturbances (double vision, complete or partial vision loss, usually one eye at a time, pain when moving the eyes, involuntary eye movements, “veiling” in front of an eye). These disorders are caused by optic neuritis (optic nerve damage). They constitute the first symptom in about 20% of cases.
  • Of abnormal sensations (sensory loss): brief pain, tingling or printing electric shocks. These are especially felt when you move your head.
  • Numbness or weakness in one or more limbs.
  • Abnormal tiredness
  • Tremors and difficulty in controlling his movements (gait disorders, for example).
  • Loss of balance.
  • Spasms or muscle contractures (spasticity), sometimes painful.

The following symptoms, which are talked about less often, can also occur (especially when the disease is changing).

  • Speech difficulties.
  • Urinary incontinence or urinary disorders (urges, difficulty emptying the bladder, urinary tract infections, etc.).
  • Constipation.
  • Sexual dysfunction
  • Partial or complete paralysis (of any part of the body).
  • Disturbances in memory, mood or concentration
In some cases, a rise in body temperature (fever, warm bath, physical exertion) can lead to reactivation of old neurological symptoms, most often visual disturbances. This transient phenomenon is known as the  Uhthoff phenomenon  . This is not a real push since the symptoms disappear when the body temperature goes down.

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People at risk of multiple sclerosis

  • People who have a close relative with multiple sclerosis also have an increased risk of developing MS: the risk increases from 0.1% (in the general population) to 1% to 3%. However, multiple sclerosis is not a hereditary disease. Several genes (including the HLA DRB1 gene) may cause susceptibility to disease, that is, an increased risk of developing it. Scientists are also exploring the link between genes and the timing or severity of the disease.
  • The women .
  • Descendants of North Europeans are predisposed to multiple sclerosis. The people of Asia, Africa and the Native Americans are the least affected by the disease.
  • People living in high latitude in the Northern Hemisphere or Southern Hemisphere or who lived there for the first 15 years of their life. The disease is 5 times more common in northern or temperate regions (such as North America and Europe) than in tropical and southern climates. The “spared” area is on the periphery of the equator, between 40 ° N latitude and 40 ° S latitude. We do not yet know the reasons for this “gradient”, but vitamin D (produced during exposure to the sun) could play a role.
  • People with a problem thyroid likely autoimmune , those with type 1 diabetes or inflammatory bowel disease are slightly more at risk.

Risk factors for multiple sclerosis

Studies of identical twins (who have the same hereditary background) reveal that environmental factors play a predominant role in the onset of the disease. Take the fictional example of Julie and Sophie, real twins aged 30. Julie has had multiple sclerosis since she was 25 years old. The risk that Sophie suffers from multiple sclerosis as her twin sister is estimated at 30%, while it should be 100% if multiple sclerosis was solely of genetic origin. It is therefore mainly environmental factors that trigger the disease. This is probably a conjunction of many factors, not just one event.

The following risk factors are presented as assumptions .

  • Have a vitamin D deficiency . The distribution of multiple sclerosis cases worldwide (more cases in the sunniest countries) has led researchers to assume a link between vitamin D and the risk of multiple sclerosis. Indeed, vitamin D is produced by the skin under the effect of exposure to the sun. Low sunlight, leading to vitamin D deficiency, may be related to the onset of the disease.

    Several studies have assessed the relationship between vitamin D levels in the blood and the risk of multiple sclerosis. In 2004, a study of two cohorts with a total of 187,563 nurses found that women who take a daily supplement of vitamin D (400 IU or more) reduce by 40% their risk of suffering from multiple sclerosis. In 2006, a survey of US troops showed that those whose vitamin D levels were highest had a lower risk of developing multiple sclerosis. In an article published in 2013, it is estimated that the risk of developing multiple sclerosis is reduced by 30% in women with the highest levels of vitamin D compared to those with the lowest levels. In addition, vitamin D levels are low in the majority of people with, especially at the beginning of the disease. Finally, studies on mice show that vitamin D may reduce the number of relapses and slow the progression of the disease. Unfortunately, the current data do not allow determining if vitamin D supplementation can influence the evolution of the disease in humans.

  • Have contracted the Epstein-Barr virus . This virus, implicated in infectious mononucleosis, has been incriminated by several studies in the occurrence of the disease. On the other hand, no formal proof of his involvement could be made. In June 2010, a study of 900 people showed that the risk of multiple sclerosis increases after infection with Epstein-Barr virus (EBV). In 2006, the same researchers had shown that sufferers have higher than normal EBV antibody levels. Finally, a recent meta-analysis involving 18 studies and more than 19 000 people, found that the fact of infectious mononucleosis increases the risk of suffering from multiple sclerosis.
  • Smoking the cigarette . People who smoke 20 to 40 cigarettes a day are about 2 times more likely to have MS than non-smokers. In addition, smoking appears to aggravate symptoms in people with and accelerate the evolution of forms relapsing to progressive forms.
  • Consume a lot of animal fat . Multiple sclerosis is more common in people whose diet is rich in animal fat and lower in those who consume mainly polyunsaturated fatty acids. Since northern populations generally have a higher animal fat diet, it is difficult to isolate the impact of diet from that of geographic location. As mentioned earlier, multiple sclerosis is 5 times more common in northern or temperate regions than in tropical and southern climates.
  • Being in contact with chemical solvents in the workplace.

Notes. We find in the scientific literature, data revealing that the port of mercury amalgam fillings increases the risk of multiple sclerosis and also aggravates the symptoms. However, most of these data come from studies whose scientific quality is considered low. Having had several mercury amalgams for years may increase the risk of suffering from the disease, but this has not been clearly demonstrated. Thus, doctors generally consider that dental amalgam is safe.

In France, following a massive vaccination campaign against hepatitis B in 1994, a study had suggested a causal link that was never confirmed later. Epidemiological studies have shown no link between vaccination against hepatitis B and the occurrence of multiple sclerosis.

Prevention of multiple sclerosis

Can we prevent?
There is currently no way to prevent multiple sclerosis as its cause is unknown. Individuals at risk of multiple sclerosis could put the odds on their side by avoiding as far as possible the hypothetical risk factors listed above.

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Medical treatments for multiple sclerosis

Although multiple sclerosis is considered an incurable disease, medical research has still found medications that alleviate symptoms relatively effectively and slow the progression of the disease. The earlier the treatment is started, the greater the chance of reducing the number of relapses.

Treatment of relapses

Flares do not necessarily require treatment, as they usually end up subsiding within a few days. Corticosteroids, such as oral prednisone and intravenous methylprednisolone, are prescribed to reduce inflammation and reduce the duration of relapses. Side effects (insomnia, increased blood pressure, mood fluctuation, fluid retention, and osteoporosis) can be significant. Plasmapheresis (plasma exchange) is an approach that can be used as well. The liquid portion of a portion of the blood (plasma) is removed and separated from the blood cells. The blood cells are then mixed with a protein solution (albumin) and injected into the body. Plasmapheresis can be used if the symptoms are recent, severe and if they have not responded to steroids.

Background treatments

Background treatments help reduce the frequency of relapses and slow down the course of the disease. They are usually offered as early as the diagnosis of relapsing- remitting MS and should be taken continuously, even in the absence of symptoms.

There is a lot of scientific evidence to show early treatment is important for reducing the frequency of relapses. In addition, the fact that the disease evolves by relapses that occur unpredictably is a major difficulty to evaluate the effectiveness of these treatments in a particular person.

There are 3 types of DMARDs: immunomodulators, immunosuppressants and selective inhibitors of adhesion molecules. These treatments reduce the activity of the immune system , thus slowing the destruction of myelin.

– Immunomodulators . They include molecules of the interferon beta family: interferon β-1a (Avonex injected intramuscularly once a week and Rebif  injected subcutaneously 3 times a week) and interferon β-1b ( Betaseron, Extavia, injected subcutaneously every 2 days).

Interferons are substances naturally produced by the body to inhibit the multiplication of viruses and stimulate the activity of certain immune cells. These are among the most commonly prescribed medications for treating multiple sclerosis. They reduce the frequency of relapses by about 30%. However, they often lead to a flu-like syndrome (fever, chills, headaches, muscle aches) and skin reactions a few hours after injection during the first 3 months of treatment. These side effects disappear afterwards. Liver damage (reversible) is common, but usually benign. Patients should then perform blood tests to monitor their liver enzymes.

Fingolimod (Gilenya) is a neuromodulator approved in September 2010 by the FDA Health Agency in the United States and in March 2011 by Health Canada. This medicine has the advantage of being taken orally. It reduces the frequency of relapsing remitting MS and slows the progression of the disease. The heart rate should be monitored for six hours after the first dose, as taking the medication usually results in a decrease in heart rate. Side effects include headaches and blurred vision. The doctor may also prescribe glatiramer acetate (Copaxone), another immunomodulator, which rarely causes side effects and no toxic effects, but requires daily subcutaneous injections. As for interferons, injections can cause local inflammatory reactions (redness, pain …). Ocrelizumab (Ocrevus) is an FDA-approved disease-modifying treatment in the United States. This immunomodulator treats both the remittent form and the progressive form of the disease. Clinical trials have shown that it reduces by half the relapse rate in recurrent disease as well as disability in both forms of the disease. Ocrevus, which is administered intravenously, produces side effects such as irritation at the injection site, low blood pressure, fever and nausea. Ocrevus can also increase the risk of certain types of cancer, especially breast cancer. Dimethyl fumarate (Tecfidera) is a medication taken orally twice a day and indicated for the treatment of patients with relapsing-remitting multiple sclerosis. It appears to reduce relapses, with side effects including diarrhea, nausea and reduced white blood cells. However, the Haute Autorité de Santé (France) considers that Tecfidera “does not present a demonstrated clinical advantage in the long-term treatment of recurrent relapsing-remitting multiple sclerosis compared to existing treatments”. Teriflunomide (Aubagio) is a once-a-day medication that can reduce the rate of relapse. However, it can cause liver damage and cause hair loss.

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  • Immunosuppressants. They are rarely used and are reserved for very severe forms of the disease (progressing rapidly and accompanied by severe attacks) or forms resistant to other treatments. It is usually a second or third-line medicine. Mitoxantrone is not officially approved by Health Canada for the treatment of multiple sclerosis, but some doctors prescribe it. This medicine is usually used to treat cancer. Its effectiveness is low in multiple sclerosis, and its potentially toxic effects are important. Indeed, this immunosuppressive drug can be harmful for the heart and is associated with the development of blood cancers. As a result, its use in the treatment of multiple sclerosis is extremely limited. Mitoxantrone is usually only used to treat severe and advanced severe sclerosis. Another oral drug, cladribine, may soon be on the market. According to results published in 2017 on the efficacy and safety of cladribine (American Academy of Neurology Annual Conference, Boston, USA), a subgroup of patients with a higher risk of progression of Disease presents a reduction of more than 80% in the risk of progression of disability with cladribine, compared to placebo. Alemtuzumab (Lemtrada) is a medication that helps reduce relapses in people with relapsing sclerosis by attacking white blood cells. Given the serious adverse effects of the product,
  • Selective inhibitors of adhesion molecules (ISMA). It is a newer class of drugs that prevents certain cells of the immune system (T cells) from entering the brain and triggering an inflammatory process. The first registered ISMA in Canada (in 2006) is natalizumab (Tysabri), a type of protein called a “monoclonal antibody”. It is used to treat the relapsing form to reduce the frequency of relapses. It is reserved for patients whose condition does not improve with other treatments or who do not tolerate them. It may be considered a first-line treatment for some people with severe stage multiple sclerosis. Natalizumab increases the risk of progressive multifocal leukoencephalopathy,

Treatments of progressive forms

While DMARDs are relatively effective against relapsing-remitting MS , they have little effect on progressive forms (primary or secondary). Some immunosuppressants, such as cyclophosphamide or mitoxantrone, are sometimes used without much effectiveness. Several clinical trials are underway (including one with fingolimod) to try to find effective therapeutic strategies for these forms.

Relief treatments

Many medications and treatments can be used to relieve the many symptoms, including fatigue, muscle spasms, pain, sexual dysfunction and urinary disorders. Here are a few.

  • Physiotherapy and rehabilitation. These are important aspects of care. The goal of rehabilitation is to preserve certain functions (such as walking), to reduce complications (urinary disorders, spasms) and to learn to live better with a disability. If necessary, the physiotherapist or occupational therapist may also propose and adapt technical aids (cane, wheelchair, etc.) to facilitate daily life.
  • Against pain. Neurontin (an anticonvulsant) and Elavil (a tricyclic antidepressant) are usually effective. Sativex, a cannabis-based medicine, can also be used (as a spray under the tongue or inside the cheek). Over-the-counter acetaminophen and ibuprofen may be helpful on occasion.
  • Against muscle spasms. Muscle relaxants (Lioresal, Zanaflex) combined with stretching exercises in physiotherapy or occupational therapy will help reduce leg spasms, which can be painful.
  • Against fatigue. Fatigue is extremely common in people with multiple sclerosis and can significantly alter quality of life. In addition to adapting your daily life to fatigue, you can take certain medications, such as amantadine or methylphenidate.
  • Against urinary problems. Several medications may be prescribed to increase muscle strength of the bladder or sphincter and limit leakage.
Canadians with multiple sclerosis can use smoked marijuana to relieve acute pain and persistent spasm, as stipulated in the Medical Access to Marijuana Regulations. For more information, visit Health Canada’s Medical Access to Marijuana Division Webpage (Sites of Interest section).

Oxygen treatment in hyperbaric chamber. This treatment consists of inhaling, in a box, pure oxygen at a pressure higher than normal. It was extensively tested in England from 1983 to 1987. Many patients reported benefit, with the treatment appearing to improve the function of the bladder and bowel. However, none of the double-blind controlled studies in this area have demonstrated a positive effect on the objective endpoints of the disease. For this reason, Health Canada does not support the use of this therapy for multiple sclerosis.

The experimental treatment of Dr.  Zamboni

In 2009, an Italian doctor Paolo Zamboni has hypothesized that MS may be related to poor circulation of blood in the veins of the neck. Poor drainage of venous blood from the brain could damage neurons, leading to symptoms of multiple sclerosis. D r  Zamboni named this disease venous insufficiency (or vascular) Chronic Cerebrospinal (CCSVI) .

According to a preliminary study conducted by Dr. Dr.  Zamboni from 65 people with multiple sclerosis, a surgical procedure called angioplasty could overcome this vein problem and decrease the symptoms of multiple sclerosis in some cases. Angioplasty consists of “opening” the veins by introducing a small balloon or a vascular prosthesis (which maintains a good opening of the veins). Doctors already use this technique for other types of health problems, for example to dilate the arteries of the heart to prevent a heart attack.

This promising study has generated a lot of hope for people with this disease, but Dr. Zamboni’s hypothesis has not been validated by other studies. Nevertheless, some private clinics (Poland, Bulgaria, Germany, etc.) offer this treatment based on Dr.  Zamboni’s experiences.

The College of Physicians of Quebec, the Association of Neurologists of Quebec and the Association of Radiologists Quebec advice against this expensive treatment whose effectiveness is uncertain, especially as the procedure can be risky (headache, displacement of the prosthesis, formation of a clot). In 2010, Dr.  Zamboni himself reiterated that this procedure was not recommended outside of clinical trials.

Nine clinical trials are underway (7 of which are funded by the Multiple Sclerosis Society of Canada) to evaluate the efficacy and safety of angioplasty and to determine the proportion of patients with multiple sclerosis or multiple sclerosis , actually have venous insufficiency. According to the results of one of these, published in April 2011, it seems unlikely that chronic cerebrospinal venous insufficiency (CCSVI) is a cause of multiple sclerosis. It could rather occur as a result of the disease.

Unfortunately, these results published in 2016 indicate that this treatment consisting of dilating the veins of the neck (veinoplasty) does not significantly reduce the symptoms of multiple sclerosis, compared to the placebo group. Of the 104 patients with multiple sclerosis, 49 had veinoplasty. Those who saw their quality of life improve were as numerous in the treated group as in the placebo group.

 

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Adapt your way of life

Here are some ways to reduce fatigue and improve quality of life . Check with multiple sclerosis associations and foundations for more detailed information on this topic.

To rest . Fatigue, one of the most common symptoms, often appears early in the illness. It is therefore important to preserve one’s energy by allowing periods of rest or relaxation, especially before an activity.

Exercise regularly . Contrary to what has been said for a long time, the physical effort does not trigger any outbreaks. On the contrary, those who continue to remain active through activities adapted to their physical abilities tend to have milder symptoms and slower disease progression. Moreover, the positive effect on morale is not to be neglected. A physiotherapist can be consulted for this purpose.

Better manage stress . It is recommended to reduce stressors and simplify life. Getting help is certainly desirable. Behavioral therapy or psychotherapy can help to better understand the source of stress and ways to overcome it. Regular practice of relaxation techniques can also improve well-being.

Participate in a support group Participating in meetings, conferences and various activities helps to better understand the disease and exchange practical tips with others in the same situation.  Avoid coffee, alcohol and tobacco. These stimulants of the nervous system tend to aggravate the symptoms.

Protect against infections . Frequent hand washing is the most effective measure. Minor respiratory infections or sinusitis have often been reported as relapses.

Avoid sudden temperature differences . For people who have these differences that trigger or exacerbate symptoms.

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