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Multiple sclerosis: the disease

Multiple sclerosis (MS) is the most common neurological disorder among young adults and often results in a handicap. In Belgium, it affects some 13,500 people (2018). It is an auto-immune disease in which the body attacks its own tissues. The immune attack in MS targets the central nervous system, including nerve fibres and the myelin sheath that insulates these fibres as well as the cells that generate nerve impulses and those that produce and sustain the nerve sheath. These lesions are well-localised and are called "plaques".
From a clinical point of view, in most cases the course of the disease can be divided into two distinct phases. The first is characterised by relapses or "flare-ups" and remissions (inflammatory phase); the second by the progressive disappearance of the relapses and by the onset of an irreversible disability which gradually worsens (degenerative phase). More rarely, some patients start with a progressive course and never have a relapse, while others develop only very slight disabilities, even after many years.
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The diagnostic is based on a key clinical characteristic of MS, namely its "multiplicity in space" (the occurrence of several lesions) as well as its "multiplicity in time" (unforeseeable occurrence of relapses and remissions). Currently, Magnetic Resonance Imaging (MRI) enables doctors to observe the lesions and to carry out much more accurate diagnosis at a much earlier stage.
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For some years now, drugs have been available which counter the inflammatory mechanisms and diminish, to some extent, the frequency and seriousness of the relapses. Current research focuses on medications capable of countering the degenerative processes and slowing down the progression of disability.


An inflammatory disease of the central nervous system
Multiple sclerosis (SEP in French / MS in English and Dutch) is an inflammatory disease of the brain and of the spinal cord, which together make up what is called the central nervous system (CNS). The inflammation occurs essentially in the white matter of the nervous system. This is made up of the extensions of the nerve cells, while these cells themselves constitute the grey matter. These extensions, which can be very long and are called axons, connect the nerve cells with one another and these cells with the rest of the body. Electrical signals pass along the axons carrying information between the different nerve cells. These axons are covered by a sheath called myelin. This myelin sheath has a protective function as well as maintaining the speed of the electrical connections. Scientists believe that the inflammation encountered in MS is directed against the components of the myelin leading to demyelination. Areas where the myelin sheath has been lost, after acute inflammation, become areas of scar tissue. The electric impulses move across them less rapidly and because of this some symptoms of the disease appear and persist. For a long time it was thought that demyelination was the most important process of the disease and that the deterioration of the nerve cells (the neurones) and their extensions (the axons) only happened later in the evolution of the disease. But today, it is accepted that the nerve cells and their extensions are threatened right from the onset of the disease. This early deterioration probably plays an important role at a later stage, when the disorders increase in the progressive phase, and it is perhaps the cause of the irreparable neurological sequelae that follow it.
Recently, it was discovered that mechanisms of regeneration are triggered after an episode of demyelination and that new cells capable of synthesising myelin sheaths are produced. It is not yet known why this regeneration of the myelin is not sufficient in the majority of people suffering from MS. It is likely that the injuries suffered by the nerve fibres are responsible for this insufficient remyelination.

Dynamic progression of the disease in space and time
MS is characterised by the progression of the lesions in time and space. By "space" is meant lesions dispersed in different foci of inflammation within the central nervous system, which lead to very different disorders depending on where they are found.
By "time", is meant the successive onset of new symptoms or the reoccurrence of former symptoms that had disappeared. It has become possible to visualise the disease thanks to imaging techniques and the appearance or the disappearance of new symptoms can be linked to observed lesions. In the primary progressive form of the disease, progression over time is characterised by the increase in neurological disorders over a year at the minimum.

Conclusion: Multiple sclerosis is an inflammatory disease that attacks the brain and the spinal cord at different locations and at different times. The protective myelin is damaged, which interferes with the conduction of nerve impulses. It is becoming more and more certain that this deterioration occurs right from the start of the disease. This explains why the neurological disorders persist while episodes of inflammation are responsible for the exacerbations.


Since foci of inflammation can be disseminated throughout the white matter of the central nervous system, the range of symptoms in MS is particularly diverse.
In this chapter, we discuss the most frequent disorders and their treatment. We particularly emphasise the cognitive and mental disorders because of the important progress that has been made recently in this area.

Visual disturbances
1. Types of visual disorders
Optic neuritis, inflammation of the optic nerve, is frequent in MS. It presents as though the vision is veiled in that eye, accompanied by pain when the eyeball moves. Contrasts are less distinct and colours are greyer. The central part of the field of vision is generally affected. Sight can also be disturbed by eyes oscillating and jerking (nystagmus). Patients can also complain of double vision (diplopia).
2. Treatment
It is difficult to treat the loss of sight, particularly in cases of optic neuritis. But we must add that recovery is often almost complete. For diplopia, patients are generally advised to cover one eye temporarily. Prisms can also improve the sight in certain circumstances. Certain forms of nystagmus can be treated by medicines, with a generally moderate efficacy.

Disorders of sensory perception and pain
1. Types of disorder of the sensory perception
Different or reduced sensory perception is a disorder frequently present in MS. The loss of sensory perception can be due to lesser perception of contact but also to a lesser sensory perception to heat; it can also result from a poor perception of the movement and of the position of the joints. The latter problem therefore causes difficulties with grasping objects or when walking, although the patient is not suffering from any lack of strength. Pain is not the most frequent symptom in MS. Trigeminal neuralgia (searing pain in one half of the face) and diffuse burning pain in the legs are most often observed. Finally, Lhermitte’s sign is a disagreeable but not painful sensation, a sort of electric shock from the neck to the extremities, occurring when bending the back of the neck. It indicates a lesion in the cervical spinal cord.
As well as these pains caused by the disease itself, pain can result indirectly from the spasticity and the hypertonia of the muscles and joints.
2. Treatment
Nerve pain such as trigeminal neuralgia can be reduced or repressed by specific treatment. Carbamazepine is the recommended treatment in the first instance. Other medicines can also be given, known for treating epilepsy. In severe cases, a surgical intervention can be considered. For other forms of pain, anti-neuralgia medicines can be added and nerves can be treated by infiltration or stimulation.

Motor disorders
1. Types of motor disorders
Lack of strength and spasticity are the most serious motor disorders. The lower limbs are often the first to be affected by the lack of strength and this causes movement disorders. The upper limbs are often spared for quite a long time. In the primary progressive form of MS, movement disorders are the most serious. Movement disorders are occasionally the only symptom with this form of MS.
With a chronic lack of strength is associated spasticity (stiffness) of the weakened limbs. This stiffness can help the patients to stand up and to walk. But in the long run, it can be disabling and painful. It can also increase the risk of bed sores, and hamper bodily hygiene and nursing care.
2. Treatment
If strength is lacking in the limbs, it is essential to pay particular attention to mobilisation. Exercises have to be performed (physiotherapy) to maintain the flexibility of the joints and preserve the remaining muscle strength. The spasticity increases in the presence of fever, urinary infections, constipation and pain. By preventing the onset of these factors and by treating this genre of disorder, spasticity can be avoided. Regular exercise (physiotherapy) and the application of cold can also bring relief. Some anti-spastic medicines can also reduce spasticity. They allow the muscles to relax or become looser. But they have to be used with caution because of their side effects. If the spasticity becomes serious, a muscle relaxant can be injected directly into the cerebrospinal fluid, which enables the dosage to be increased in exactly the right place (the spinal cord) and at the same time limits the side effects.

Disorders of coordination and balance
1. Types of coordination disorders
Difficulties with coordination of the movements can lead to interference with moving and the precision of using the hands. Tremors that intensify as the hand approaches its target prevent it from making precise movements. Joining words and phrases can also be difficult, which interferes with speaking in a characteristic manner.
2. Treatment
Medication can remedy tremors when they interfere with day-to-day activities. In serious cases when one hemisphere is much worse affected than the other, neurosurgical intervention can be recommended. Speech difficulties can be improved by speech therapy exercises and there are ways to improve disorders of the balance, primarily through physiotherapy.

Urinary and intestinal disorders
1. Types of urinary and intestinal disorders
Inflammation due to MS can also have an effect on the parts of the central nervous system responsible for the urinary and intestinal system. Two types of disorders can be distinguished in cases in which the bladder is disturbed, which occasionally combine. On one hand, the detrusor muscle becomes hyperactive and the patient constantly has the feeling of having to urinate. On the other hand, the neck of the bladder does not dilate sufficiently so that the bladder cannot empty completely. These two factors can lead to accidental or involuntary losses of urine (incontinence). It is less frequent to encounter faecal incontinence in MS. Constipation is frequent in contrast and is aggravated by reduced mobility.
2. Treatment
Hyperactivity of the bladder can be controlled with medication. In some cases, pelvic floor exercises can be beneficial. If the bladder does not empty completely, another type of medication can be effective. If this is insufficient, one might consider using a catheter intermittently or continuously.
To counter constipation, it is essential to get sufficient exercise and to eat a balanced diet that is rich in fibre. A mild laxative can be used.

Sexual disorders
1. Types of sexual disorders
Although sexual disorders are rarely touched on during consultations, they are nevertheless frequent in many patients suffering from MS. They are also the cause of many relationship problems. In men, they cause less good quality erections; in women, reduced vaginal secretions and difficulty reaching an orgasm. Reduced sensory perception, spasticity of the lower limbs, fear of incontinence and the psychological burden of the disease play an important role here.
2. Treatment
For men, there are several medicines for treating erectile dysfunction. For women, we can currently only try to treat the factors mentioned above. Dialogue within the couple often enables tensions and feelings of blame to be released.

Cognitive disorders
1. Types of cognitive disorders
Approximately half of the people who are victims of MS suffer from slight cognitive or mental disorders. These disorders are often insidious and relatively non-specific. They can be classified in the following categories: attention disorders, slower information processing and learning difficulties. Maintaining the attention (concentration) and retaining mental flexibility (being able to do several things at the same time) is found to be very or too difficult. Information processing is often slowed. In the memory functions, poorer memory of recent events is observed.
It must be noted that the severity of the cognitive and mental disorders is not connected with the duration of the disease, the type of MS or the physical condition of the patient. Some people can be in a wheelchair and not suffer any cognitive impairment, while others will have cognitive problems but no problem getting about or walking.
In contrast, there is a link between cognitive disorders on the one hand, and the severity of the lesions visible to cerebral imaging on the other hand. A small proportion of patients (approximately 5%), go into a significant cognitive decline which could be described as dementia.
2. Consequences
Nowadays, the majority of scientists concur in recognising that even mild cognitive disorders can have a serious impact on the patient’s personality, ability to work, quality of life, social relationships as well as on the possibilities of rehabilitation. Cognitive and mental disorders have been the subject of detailed studies in recent years and some scales of measurement have been devised to evaluate them. In studies of new medicines, these scales are often used in order to be able to describe the patient’s progress better.
3. Treatment
Today, compensatory mechanisms are often introduced to compensate for the cognitive disorders. By doing this we endeavour to create around the patient a fixed structure and stability in his/her environment so that fewer unexpected events occur. The context thus created enables the patient to as it were develop an automatic pilot response for the majority of their daily tasks.

Mental disorders
1. Types of mental disorders
Some recent studies have shown evidence of frequent changes of mood in people suffering from MS. These changes often present in the form of depression. A psychotic profile can occasionally appear, sometimes preceded by depression (bipolar psychosis) or followed by depression.
Approximately half of patients develop serious depression at least once in the course of the disease. Depression is characterised by black thoughts, a lack of desire, a lack of initiative, reduced appetite and sleep disorders. Suicide is also more frequent in MS patients than in the rest of the population.
The reason why people suffering from MS develop depression is not clear. Several psychological factors play a role here: acceptance of the disease, loss of possibilities, social isolation, family and relationship difficulties, etc. Some studies have shown that depression is more frequent in patients presenting lesions in the brain in contrast to those in whom the lesions are mainly situated in the spinal cord. This observation implies that certain brain lesions increase the frequency with which depression appears. But other factors without doubt play a role. Some medicines have psychological side effects, which are less understood. Agitation, confusion and euphoria often appear for example during and after cortisone treatment.
2. Treatment
Treatment has to include components of drug and psychological support. The part accorded to these two components depends on the patient’s difficulties and his/her wishes.

Paroxysmal disorders
1. Types of paroxysmal disorders
Paroxysmal disorders are characterised by their brevity: a few seconds or minutes. This distinguishes them from flare-ups or exacerbations which can last for days, weeks or even months. Paroxysmal disorders are generally repetitive; they occur in groups of five to ten and can be repeated dozens of times a day. They often occur spontaneously since some factors such as anxiety, stress, hyperventilation, some movements and some stimuli such as heat or exercise can trigger these attacks. The clinical symptoms are varied: disorders of the sensory perception (pain in the face, backaches, shooting pains, short episodes of pins and needles, burning sensations, itching) and motor disorders (muscle spasms and cramps). More rarely, paroxysmal disorders of speech or of the balance can be seen.
Paroxysmal disorders, which appear repeatedly for a very brief time, must not be confused with symptoms appearing in very hot places or after physical exercise. These symptoms, which are caused by the increase in body temperature, are the sign of incomplete recovery following a previous inflammatory episode and are not the consequence of a new lesion of the nervous system.
2. Treatment
Carbamazepine and other medicines for epilepsy are often prescribed with success in cases of paroxysmal disorders.

1. Types of fatigue
Two types of fatigue can arise in MS. The first form is in connection with physical handicaps. Thus, a patient with a vision problem will tire more quickly when they are reading. A person with a lack of strength in the legs will have the distance they can walk reduced by fatigue in the lower limbs. But MS is also characterised by tiredness that is not linked to physical deterioration. There is a feeling of exhaustion, a lack of energy when faced with simple everyday tasks. This phenomenon is experienced by 75% of patients suffering from MS. In some cases, it is even the most important symptom that prevents them from performing professional and social activities. The exact mechanism causing this feeling of exhaustion and overwhelming tiredness is not yet known.
2. Treatment
It is essential to adapt your lifestyle if you are going to overcome tiredness. You have to get sufficient hours of sleep and possibly start taking one or several breaks during the day. Professional activities can be adapted to fit with this, by working part time for example, or getting help with the domestic chores. As far as possible it is best to avoid sleeping pills and sleep inducers. If all else fails, some medicines can be advised.

Conclusion: The foci of inflammation in MS are situated particularly in the white matter of the brain and the spinal cord and they give rise to a variety of disorders. As our central nervous system has an executive role, all the bodily functions can in fact be involved. Currently, this disease remains incurable despite studies into the origin of MS mechanisms and the progress made in treating it. So it is essential to recognise the disorders linked to the disease in order to be able to treat them as much as possible. Given that the disease varies enormously from one person to the next, an individual approach is absolutely essential. A multidisciplinary approach is also needed to take account of all the different symptoms and their treatment.


The treatment depends on the stage of the disease
The proposed treatment depends on the stage of the disease. An easy way to present it is to divide the disease into 4 distinct stages. Each of these phases is linked to specific care and needs.
* Stage I: the diagnosis phase
This difficult period is accompanied by a degree of confusion. It is important that the diagnosis be explained clearly and communicated intelligently. Generally, this is a very difficult time. Psychological monitoring and support are recommended. There is an immense need for information. Special attention must be paid to the questions about how it might develop, the treatment options, the role of heredity, pregnancy, heat, infections, vaccinations, diet and lifestyle. The partner and/or family members will ask a great many questions and desire additional information.
* Stage II: the no or mild handicap phase
Happily, this is the longest phase for the majority of patients. A minority of patients will remain in this phase for the remainder of their lives, but it is impossible to predict who they will be. Patients in this phase are often in the relapsing-remitting stage of MS. They have need of many services and care. They seek advice and help with their relationships, their work, their housing and also their finances. They want to understand how to deal with their neurological disorders and the loss of certain functions. The treatments available at this stage are interferon beta and glatiramer acetate. In response to a very active form of the disease, chemotherapy can be tried. The limited effects of these treatments in the short term and the uncertainty of their long-term efficacy call for vigilance and close neurological monitoring of the group treated.
* Stage III: the moderate handicap phase
Patients at this stage can still experience flare-ups, but typically develop a growing neurological deficit over the years. It is important to encourage them to actively face up to their disease. Therapy tailored to their individual disorders must be considered. It is recommended to improve the communication and coordination between the services and care providers. A multidisciplinary approach is advised, the aim of which is to limit the loss of functions and the handicap as well as to improve the quality of life.
* Stage IV: the serious disability phase
The needs of the patient are complex and varied at this stage. The family is heavily involved in the care to be provided. It is necessary to arrange long-term care and services and involve professional and charitable organisations. If the patient continues to live independently, short stays in an appropriate care establishment should be arranged, if possible.


Treatments that act on disease progression
A. Interferon beta
* What is interferon beta?
Interferon beta is a natural protein, a cytokine (see chapter 2), that is manufactured by biotechnology. Interferon beta 1b (Betaferon®) is manufactured from bacteria while interferon beta 1a (Avonex® and Rebif®) is produced from mammalian cells. Interferon beta is only active if injected; Avonex® is injected into the muscle (intramuscular) while Betaferon® and Rebif® are injected under the skin (subcutaneously). In this country, Betaferon®, Avonex® and Rebif® are reimbursed under precise conditions: the patient must have a relapsing-remitting form of MS and have had at least two flare-ups in the preceding two years.
These two flare-ups must have necessitated corticosteroid treatment. The patient must also be able to get about by themself. This means that he/she must be able to walk 100 m unaided. Without reimbursement, the treatment would cost each patient approximately €1000 per month.
* How does interferon beta work?
The exact action mechanism of interferon beta is not known. It is thought that it acts at several levels and that it has an effect on certain cytokines, on the permeability of the blood-brain barrier and on other cells of the central nervous system. All these effects have the same result: to suppress the inflammatory process.
*What can be expected from interferon beta?
Current interferon beta treatment acts with partial efficacy on the inflammatory activity observed in people suffering from MS whose evolution is characterised by flare-ups and periods of improvement and in whom the neurological deterioration is moderate. This efficacy is characterised by a reduction in the flare-ups of 30% on average and a slowing of the progression of the disability. On the NMR, markedly fewer active lesions are seen. This treatment is initiated to reduce the activity of the disease and to limit as much as possible the future development of sequelae. But in principle, an improvement in the existing neurological condition cannot be expected.
Since the effect of the interferon treatment is not always evident at a precise point in time, and since the side effects – particularly at the start of treatment – can be uncomfortable, the patient really has to be motivated to continue treatment. It is important that the patient, his/her partner and family are fully aware of the realities of the treatment right from the start. This should be discussed with the neurologist. What does "less active disease" mean for the patient and his/her doctor if it is not clear how the disease would develop without treatment? In practice, some patients stop their treatment for lack of convincing results, which can be damaging in the medium term.
* What are the side effects of interferon beta?
There are two types of classic side effects. First, the flu-like symptoms which disappear after several weeks or even several months. Secondly, there are injection site reactions, particularly to the subcutaneous forms. “Flu-like symptoms” means muscle and joint pain, occasionally headache, fever and shivering. It occurs several hours after the injection and can occasionally last for up to 18 hours; taking paracetamol or another analgesic such as ibuprofen is the best way of managing it. This phenomenon generally wears off after several weeks or months. A minority of patients continue to experience these flu-like side effects after each injection. These symptoms vary considerably from one person to the next. Some people feel very ill at the start and others experience no side effects. The reaction to interferon is difficult to predict.
The side effects at the injection site also vary from one person to another. A slight and occasionally painful redness can develop at the point of injection, but rarely for intramuscular injections. To prevent this from happening, it is necessary to change the injection site, practice the injection technique well and possibly use the auto-injector (a kind of pen). If redness and small local areas of inflammation develop it is recommended to consult a specialist nurse or a doctor. Rarely the local inflammation can be bad enough to cause skin necrosis.
Interferon beta cannot be administered if a woman is pregnant or lactating because of the possible harmful effects on the child.

B. Glatiramer acetate
Glatiramer acetate (Copaxone®) is a synthetic protein made up of amino acids similar to those of the basic protein of myelin, one of the principal components of myelin.
In a double-blind study on 251 people suffering from a relapsing-remitting form of MS, the number of flare-ups was reduced by 29% in the group treated. However, the progression of the disability was not affected to a significant extent. This treatment also has an effect on the number and the activity of the lesions seen by NMR. This product has to be injected every day subcutaneously. The side effects are most often limited. However, redness at the injection site is common. Glatiramer acetate cannot be administered during pregnancy. In this country, Copaxone® is reimbursed under the same conditions as interferon beta in the relapsing-remitting form of MS.

C. Mitoxantrone
Mitoxantrone (Novantrone®) is a synthetic immunosuppressant that acts long-term on the immune system. Several clinical studies have demonstrated its action on the number of exacerbations in MS, on its slowing effect on neurological deterioration and on its favourable action against the progression of disability. The quantities used and when they are administered differ according to the studies. Even so its cardiological toxicity cannot be ignored. This limits how long it can be used for. Moreover, the risk of leukaemia following this treatment is slightly higher than that of the general population. Mitoxantrone is contraindicated in pregnancy.

D. Natalizumab
The foci of inflammation characteristic of MS develop in the brain and the spinal cord because some white blood cells are able to cross the blood vessel wall and infiltrate the central nervous system. This passage of lymphocytes is facilitated by a protein present on the surface of the white blood cells that enables them to adhere to the surface of the blood vessels. Natalizumab (Tysabri®) blocks this “stickiness” and prevents the lymphocytes from penetrating the brain and the spinal cord, which reduces the formation of foci of inflammation. This agent is administered intravenously once a month.
It has been demonstrated that natalizumab reduces the frequency of exacerbations by 66%. Its effect is also favourable in brain MRI scans. Nevertheless, this agent can only be recommended to a limited number of patients who have a particularly aggressive form of MS because a rare fatal complication has appeared (progressive multifocal leukoencephalopathy, a generally fatal infection of the central nervous system) in some patients who were simultaneously given natalizumab and interferon beta.

In what forms of MS can disease progression be modified?
A. First episode, MS is suspected
A clinical study has proven that after a first neurological episode with suspicion of MS, it is possible to delay the second episode significantly by administering interferon beta 1a (Avonex® intramuscular 1x per week) compared with the placebo group. This was also the case in another clinical study with interferon beta 1b (Betaferon®).
The results with Rebif® in a group of patients who had experienced a first attack of suspected MS are still being investigated.

B. Relapsing-remitting MS
Injections of interferon beta 1a and 1b are partially effective in patients with mild to moderate handicap presenting a relapsing-remitting form of MS. Studies with Betaferon ® (interferon beta 1b), Avonex® and Rebif® (interferon beta 1a) demonstrate almost comparable efficacy. These agents act on the clinical parameters (30% fewer exacerbation and slowed progression of disability) as well as on the imaging parameters (fewer new lesions and fewer active lesions in NMR).
However, although the differences between the forms of interferon and the modes of administration are not very great, the results of the studies demonstrate the superior efficacy for Rebif ® dose for dose. This means that the administration of a high dose of interferon beta 1a (Rebif® 3 x 44 mcg per week subcutaneously) gave better results for the disease than a lower dose (Rebif® 3 x 22 mcg per week subcutaneously).
However, for Avonex®, the superiority of the standard dose (30 mcg) compared with a double dose (60 mcg), once a week by the intramuscular route, has not been demonstrated. Regarding Betaferon®, a study is underway on the comparison between the standard dose and a double dose. Daily injections of glatiramer acetate seem to give similar results. Regarding the monthly infusions of natalizumab (Tysabri®), they seem more effective than these therapies, but because of the risk of multifocal leukoencephalopathy, this treatment is not indicated in the first instance. Mitoxantrone is also reserved for the serious forms of MS because of the possible side effects.
The long-term effects of these disease-modifying treatments are not yet fully understood. For interferon beta, it is known that neutralising antibodies threaten to reduce the efficacy of the treatment after several years in some patients. Additional studies are necessary.

C. Secondary progressive MS
In the secondary progressive form of MS with continuing flare-ups, the same principles apply as those used for the relapsing-remitting forms. In contrast, studies using interferon beta in pure secondary progressive forms, without flare-ups, have not yielded significant results. In other words, it has not been proven that interferon beta might delay the progression of disability when it is no longer the consequence of flare-ups. No data are available for glatiramer acetate or natalizumab in relation to their effect on disease progression in the absence of flare-ups. The role of the immunosuppressants and chemotherapy is still being debated. Mitoxantrone (Novantrone®) has been studied and several positive studies demonstrate a reduction in flare-ups and in the progression of the disability compared with placebo. Its cardiotoxic effect and the increased risk of leukaemia are, however, limiting the usage and the duration of administration in practice.

D. Primary progressive MS
This group of patients is not eligible for the treatments mentioned above because there is currently no scientific evidence for the efficacy of these treatments in this form of the disease.
How is the efficacy of a treatment evaluated?
The patient and doctor can often evaluate the effect of the treatment on the evolution of the disease themselves. The number and the severity of flare-ups as well as any neurological deterioration are a first measure of it. However, since disease progression cannot be predicted and since today’s treatments cannot cure the disease or stabilise it completely, it is difficult to predict disease progression during the treatment. The effect of a treatment is therefore sometimes difficult to evaluate in an individual patient.
The collection of reliable data on dozens of patients throughout the world might in the future enable a mathematical model to be constructed; this would portray the evolution of the MS by formulae (also incorporating clinical and imaging data). The international project "Sylvia Lawry Centre for MS research" was founded with this aim. The creation of a "virtual" placebo group will enable clinical studies to be shorter and less onerous. This project is supported by the international federation of MS associations.

Treating exacerbations
Corticosteroids have their place in treating exacerbations. In principle only exacerbations of moderate to serious intensity are treated in this way: 500 to 1000 mg of methylprednisolone are administered daily by IV infusion for 3 to 7 days. An oral regimen is occasionally recommended to follow it with larger or smaller doses of cortisone. The clinical studies available on the effect of this treatment are limited in number and the present schedules are so different that it is difficult to compare the results. It is generally acknowledged that taking corticosteroids promotes a more rapid recovery from the symptoms of an attack. But it has not been possible to demonstrate a clear effect when it comes to the remission obtained, the frequency of the flare-ups and the neurological deterioration in the long term.
It is necessary to avoid the chronic administration of cortisone because of the known side effects (particularly hypertension, diabetes, decalcification of the bones, cataracts).

Experimental treatments
These are treatments that are still being researched. They may be treatments whose efficacy has not yet been proven. So we are talking of pilot studies. The result of a pilot study tells us the effects of the treatment as seen by magnetic resonance and clinically. This type of study is essential for a larger scale study to be planned.
There can also be treatments that have already proved promising in a relatively small number of patients. So it is necessary to confirm these results within a study of greater scope in a particular group of patients. Examples are treatment with fingolimod (FTY720) or cladribine.

Alternative medicine
Alternative medicines are commonly taken by MS sufferers. The multitude of hypotheses on the origin of the disease is probably one of the causes of this phenomenon, together with the variations in disease progression, the large individual differences and the absence of curative treatment. All anecdotal evidence of improvement or cure always receives excellent press. The media play a role here.

Some anecdotal reports have demonstrated the favourable impact of cannabis on pain, urinary disorders, tremors and spasticity in MS. This has resulted in the often illegal use of cannabis for various forms of MS. It is estimated that approximately half of MS patients have used cannabis. Some studies have been properly conducted to test the efficacy of cannabis on spasticity but also on pain, tremors, urinary disorders and quality of life. It seems that cannabis has no effect on spasticity, while it has yielded some beneficial results in urinary incontinence and neuropathic pain. Nevertheless, the results obtained are difficult to interpret because the dosages used in the studies are very different, even within the same study. In addition, as patients are aware of whether or not they are using the real substance, we cannot really talk of double-blind studies. Finally, in the long term, cannabis can have harmful effects, particularly on the memory.

Other alternative medicines
Two-thirds of the MS patients in the United States have experimented with an alternative therapy such as acupuncture, reflexology, homeopathy, acupressure, aromatherapy, mega doses of vitamins, biotics, snake venom, the extraction of dental fillings, etc. In parallel, standard courses of vitamins and amino acids, plant extracts (less well described), cell therapy and vaccinations are very popular. Some treatments are not without risk such as apitherapy (with bee venom) or the intravenous injection of calcium or magnesium. Unfortunately, none of these therapeutic programmes has shown a reliable effect in rigorous clinical studies.

Dietary measures
At present there is no scientific proof that a particular diet has an effect on the progression of MS. Nevertheless, it seems logical to support the immune system and the central nervous system by a healthy diet. A balanced diet helps the sufferer to stay in shape and reduce the fatigue and lack of energy to a minimum. The general dietary guidelines for MS sufferers do not differ greatly from the dietary rules recommended to the whole population.
It is advisable to eat a varied diet, including sufficient proteins, carbohydrates, low-fat dairy products, vegetables and fruits. It is necessary to limit the amount of fat consumed and reserve a large part of the fat intake for polyunsaturates. It is also necessary to limit foods with a high sugar content. Vitamin and mineral supplements are not necessary if the diet includes sufficient vegetables and fruits. It is advisable to consult a doctor to avoid overdosing on some of these supplements. It is also important to consume essential fatty acids. The latter are found in sunflower oil, fish oils, certain types of fish such as tuna, salmon and sardines but also in green vegetables (particularly broccoli, spinach, green cabbage, Brussels sprouts and salad).
It is also recommended to drink 1 to 2 litres of water or low-sugar drinks per day. These liquids help prevent urinary infections and constipation. Alcohol should be consumed in moderation.

Conclusion: No medical treatments have so far led to the total stoppage of disease progression. In contrast, in a group of patients that present exacerbations, some recent clinical studies have proved that it is possible to reduce the activity of the disease. The loss of function due to the disease is also reduced by these treatments (temporarily). But not enough is yet known about the therapeutic effects and the side effects of these treatments in the long term to predict the future. Alongside these preventive treatments, courses of corticosteroids are occasionally used ¨does not look nice in printing proof in the middle of the i” to reduce the length of an attack. Other experimental treatments are currently used on a small scale in the context of rigorously controlled studies. Alternative medicines are on the other hand taken a great deal, probably because of the limits of traditional medicine. Their use is rarely corroborated by reliable scientific data.


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