Multiple Sclerosis (MS)

Multiple sclerosis (MS) belongs to the group of chronic diseases that affect the brain, spinal cord and optic nerve. The word "multiple sclerosis" is composed of the word "skleros" (=hard) and "multiplex" (=multiple). The clinical picture is characterized by characteristic inflammations of certain nerve structures, which in turn can cause various complaints, such as visual disturbances, sensory disturbances, pain or paralysis. Such an outbreak of the disease is called an "attack".

MS is an autoimmune disease in which the body's own defence cells (immune cells), which are normally responsible for driving out viruses, bacteria or other germs, are directed against structures of the patient's own body. As a result, the immune system attacks the sheath of the nerve fibres (myelin sheath), causing inflammation in some areas of the brain, optic nerve or spinal cord (central nervous system, CNS). Continuous destruction of the myelin sheath occurs. In this case, it is called demyelination.

In addition, the nerve fibres and nerve cells are also affected by the damage. The transmission of nerve signals is no longer intact, as is the case in healthy individuals. Sometimes there are also nerve failures. These nerve failures can vary depending on the area of the CNS in which the inflammation (inflammatory foci) occurs. For this reason, MS is often called "encephalomyelitis disseminata" because "disseminata" means "scattered". "Encephalomyelitis" stands for basic processes in the brain in MS: "enkephalos" means "brain" and the suffix "-itis" can be translated as the word "inflammation".

The course of multiple sclerosis manifests itself in different forms. In most cases, there is a complete regression of the symptoms before a new relapse occurs.

90 -95 % of the diseases have a relapsing course. However, in 30-40% of patients, there is also a continuous deterioration without relapses. Some sufferers may also have the disease without relapses from the beginning and progressively worsen.

MS first appears in young adulthood between the ages of 20 and 40. Women are more often affected by the disease than men. So far, there is no known complete cure for MS. However, the course can be well influenced with medication.

Discovery of MS:

The disease was first described medically in about the late 1800s by Scottish ophthalmologist William MacKenzie. He discovered the disease in a 23-year-old man who suddenly suffered from visual disturbances and paralysis. He was later unable to speak or hold his urine. Two months later, however, the sufferer no longer showed any symptoms.

In 1868, the French neurologist Jean-Martin Charcot produced a more detailed clinical and pathological description of the complaints. He also succeeded in recording the destruction of the nerve sheaths on the basis of an autopsy. He gave the disease the name "sclerosis en plaques", which is still the common name in France today.

Inflammation and destruction:

Despite intensive research by experts, it is not yet clear exactly why people contract MS. However, it is suspected that an incorrect reaction of the immune system (autoimmune disease) plays a major role. As a result, an inflammation occurs in the area of the nervous system, in which the nerve sheaths and nerve fibres are increasingly destroyed, making the transmission of nerve impulses more difficult. The process of destruction is called demyelination. In the advanced course, the nerve fibers also perish.

Crazy immune system:

Autoantibodies have the effect of causing white blood cells (leukocytes) to attack nerve tissue, which can lead to inflammation. The foci of inflammation can occur anywhere. If they heal, scars nevertheless remain in the brain or spinal cord (plaques). Due to the inflammation, nerve impulses are now transmitted more poorly or not at all. Depending on where the focus of inflammation is located, various complaints can occur. These can be paralysis or sensory and visual disturbances. The clinical picture therefore varies from patient to patient.

Genes:

Multiple sclerosis probably also has a hereditary disposition to some extent. On the basis of studies it can be said that identical twins of parents suffering from MS show an approximately 25 - 30 % increased risk of disease than the rest of the population. For fraternal twins, the risk is about 5%. Parents and children of an MS patient still have a double to triple increased risk. With decreasing degree of relationship the danger to fall ill with MS also decreases.

It is not yet clear whether a specific gene is the trigger for the development of MS. However, it is suspected that changes in the HLA-DRB1 antigen, apolipoprotein E or the interferon gamma gene play a not insignificant role. Research has shown that MS takes a more severe course in sufferers with certain genes. Other researchers suspect the JAG1 or POU2AF1 genes to be the trigger for multiple sclerosis.

Infections:

Experts often link the onset of MS to an infection, such as a viral infection with human herpesvirus-6 (HHV-6), human endogenous retrovirus (HERV), or Epstein-Barr virus (EBV). There is as yet no definite proof as to whether these hypotheses correspond to the truth.

Adolescents and mainly adults who are infected with EBV (infectious mononuclease) probably have a two to three times higher risk of developing MS than people without EBV infection. Other germs are also suspected of being involved in the development of MS. These include the bacterium Chlamydia pneumoniae, which has been found in the cerebrospinal fluid (CSF) of MS patients more often than in healthy people. However, other studies did not provide firm evidence for this hypothesis.

Lifestyle and environment:

Environmental factors and a certain lifestyle may also contribute to the development of MS. One example is smoking, which not only increases the risk of MS but is also thought to accelerate the progression of the disease. Nevertheless, MS may not be triggered solely by an unhealthy lifestyle.

The amount of vitamin D in the body could possibly also play a role. People who were exposed to more sunlight in their childhood and thus can produce more vitamin D are less likely to suffer from MS than people with low vitamin D levels.

An example of this would be the indigenous people in Greenland, who traditionally eat a diet rich in vitamin D and are less likely to develop MS. Nevertheless, taking vitamin D supplements has not yet been shown to protect against MS.

Gender:

According to statistics, women are more likely to develop MS than men. The cause of this phenomenon may lie in as yet unknown environmental factors.

Multiple factors combined:

In all likelihood, there is not one particular factor that leads to the onset of MS, but rather an interaction of many factors is considered to be the trigger. These factors include lifestyle with dietary habits, genes, viral infections, and other environmental factors.

The extent of the symptoms depends on the place of origin of the inflammatory focus and can therefore be very different.

The first signs usually appear suddenly and with complete well-being. In rare cases, the symptoms can also develop gradually. Every third affected person first suffers from sensory disturbances characterized by numbness or tingling in the legs and arms. One in five patients initially suffers from unnatural fatigue, problems with bowel movements or the inability to walk or stand properly. Other symptoms are rare as initial symptoms.

The onset of MS is usually completely unexpected. Normally, the affected person feels fine. Within hours or days the first symptoms appear. It is rather untypical for MS that the disease becomes apparent slowly and the degree of symptoms is sometimes stronger and sometimes weaker, so that the patients hardly notice anything.

The majority of those affected are between 20 and 40 years old when the symptoms first become apparent. One third of patients initially suffer from sensory disturbances, which are manifested by numbness and tingling in the legs and arms.

About 16 percent initially complain of visual disturbances. Others suffer from a lack of strength in the arms (more rarely also in the legs), as well as disturbed bladder emptying or pain. However, it can also happen that several symptoms occur at the same time.

If there are inflammatory foci with pronounced symptoms, this is referred to as a relapse. After an episode, the symptoms usually subside until an episode occurs again at a later time. In some cases, new symptoms are added to the existing ones, which can also disappear after a certain time.

The course of the disease varies greatly from patient to patient. In some patients, the symptoms disappear completely after a relapse, while in others they remain partially present. Sometimes the symptoms increase more and more, so that relapses can no longer be identified.

More than 50 percent of patients suffer from gait and balance problems or spasticity (muscle cramps) in the course of the disease, they are afflicted by severe fatigue, have a feeling of weakness in the limbs or can no longer empty their bladder properly. In addition, men may suffer from erectile dysfunction. In three out of four patients, the vision in one eye is impaired, while others see everything twice.

In about one in two patients, insecurity in aiming and pointing movements, psychological disorders (such as depression), speech disorders, cognitive disorders (such as concentration disorders) or bowel emptying disorders manifest themselves.

Rarely but occasionally, other symptoms occur, such as headaches, pain or paralysis in the face, pain in the body, numbness or lack of strength in the arms or a tingling sensation in the neck when the head is bent.

In general, the diagnosis is very complicated because MS can manifest itself with many symptoms and some people have few symptoms while others have several symptoms at the same time.

Diagnosis is usually very difficult because, unlike other diseases, there are no typical symptoms that are unique to multiple sclerosis. Most of the symptoms can also be symptoms of another disease, such as circulatory disorders in the brain or a herniated disc. In order to be able to make a diagnosis, the following examination steps are used:

• Medical history (anamnesis)
• Physical examination (clinical findings)
• Technical and laboratory examinations (e.g. magnetic resonance imaging = MRT, evoked potentials, examination of the cerebrospinal fluid, blood tests).

While taking the medical history, the doctor asks about the duration of the complaints and their development. Some people are unaware that symptoms they have been suffering from for months or sometimes even years may be the first signs of MS. Sometimes patients describe that they once had a strange feeling in an arm or leg for a few days to weeks a long time ago, which may indicate inflammation in the spinal cord. The symptoms are often ignored and not given any further attention because they are not particularly pronounced or disappear immediately (for example, in the case of inflammation of the optic nerve). In many cases the doctor does not find a cause.

It is also important to find out whether the affected person or a family member suffers from an autoimmune disease.

Signs such as difficulties with bowel movements, problems with urination or sexual intercourse, or rapid fatigue and difficulty concentrating, as well as depressive moods should be asked about.

After taking a medical history, a physical examination is performed, during which a normal clinical and a neurological examination are made.

In addition, there is a check of the visual ability. To determine the degree of destruction caused by inflammatory foci, certain scales are used, such as the Expanded Disability Status Scale (EDSS) or the Multiple Sclerosis Functional Composite Scale (MSFC).

In order to measure attention or concentration disorders, the paced auditory serial addition test (PASAT) is performed. In this test, 60 single-digit numbers are played back on a tape recorder. The test person is then asked to add the second number to the first and state the sum. This pattern continues until the end.

In addition to the purely neurological examination, there is also a neuropsychological examination. These examinations consist of testing learning ability, language processing or memory. Certain tests are also used for this purpose.

If problems with urination occur, this behaviour can be controlled by means of a micturition protocol. In this protocol, the patient notes how often he or she urinates. The amount of urine remaining in the bladder after urination is noted (residual urine determination). In some cases, this is followed by a urodynamic examination. This is a measurement procedure that examines the functioning of the urinary bladder using pressure probes and electrodes.

To determine the extent of the disease, evoked potentials (VEP, SSEP, MEP, AEP) are determined. Potentials are electrical voltages that occur in nerve and muscle cells. With the help of electrodes, these potentials are derived and recorded after electronic amplification.

In addition, a magnetic resonance tomography (MRT) of the skull and spinal cord is performed. Inflammation foci and plaques in the brain that exceed a size of two millimeters are already visible at the beginning of the disease. An advantage of MRI over other diagnostic procedures is that changes are already apparent when the patient is still completely symptom-free.

As a further examination, cerebrospinal fluid is taken (CSF diagnostics). To obtain the fluid, the physician must insert a fine needle between the vertebrae in the area of the middle lumbar spine. An inflammation of the brain and spinal cord can be determined on the basis of such a CSF puncture. If the affected person suffers from MS, the number of certain immune cells (leukocytes, plasma cells) in the cerebrospinal fluid is increased. In this case, antibodies such as immunoglobulin G (IgG) can also be detected. In addition, the doctor can determine whether the inflammation is actually caused by MS or by germs (e.g. Lyme disease).

The following parameters are collected in the blood test:

• CBC
• Liver values
• Kidney values
• Thyroid function
• Blood sugar
• Vitamin B12
• Rheumatoid factors
• Antinuclear antibodies (ANA)
• Anti- phospholipid antibodies
• Lupus anticoagulant
• Inflammatory markers (C-reactive protein= CRP)
• Angiotensin converting enzymes (ACE)
• Lyme disease

The urine of the patient is also examined.

Mostly the laboratory values of MS patients are in the normal range. Nevertheless, they are collected in order to exclude other diseases, which can show similar symptoms. Therefore, in some cases, further blood tests are necessary, such as:

• ANCA
• ENA
• HIV serology
• HTLV-1 serology
• TPHA
• Determination of long chain fatty acids
• Mycoplasma serology
• Methylmanyl excretion in urine

Certain laboratory values can show a change under treatment with certain drugs. This is the case, for example, with therapy with cortisone: the number of white blood cells (leukocytes) decreases, whereas it increases with treatment with immunosuppressants. Blood sugar also increases when the person takes cortisone.

Since the diagnosis of MS is not easy, it can sometimes take weeks, months or even years until it is clear which disease the patient is suffering from.

So far, there is no clear therapy that promises a cure for MS. However, the same applies to many other chronic diseases, such as diabetes or high blood pressure (hypertension). One can only try to influence the course of the disease favourably, to alleviate the symptoms and to slow down the progression of the disease by means of medication and other therapies.

The therapy of MS has the following goals:

• The symptoms caused by an attack should, if possible, disappear completely.
• Further relapses should be prevented.
• Permanent disabilities should be avoided.
• If existing disabilities do occur, they should at least not worsen.

In order to achieve these goals, one can choose between the following therapy options:

• Medication
• Physiotherapy (physical therapy)
• Activation and occupational therapy (ergotherapy or psychotherapy)

However, the individual therapies show varying degrees of effectiveness. The effect of some therapies is still controversial. These include acupuncture, Bach flower therapy, meditation techniques, craniosacral therapy, hypnosis or relaxation exercises.

In the case of MS therapy using medication, a distinction can be made between three therapeutic approaches:

• Therapy of the acute attack: cortisone via the vein. If it is an acute attack, blood washing (plasmapheresis) or mitoxantrone (cytotoxic antibiotic, inhibits cell division and cell growth) is used.
• Symptomatic therapy: Treatment of non-specific symptoms, such as spasticity, pain, depression, bladder or bowel emptying disorders. Different preparations are available depending on the type of symptoms.
• Long-term therapy: Use of immunomodulatory or immunosuppressive preparations. They lead to a change or suppression of the immune system (e.g. interferons beta 1-a and beta 1-b, glatiramer acetate, azathioprine, mitoxantrone, intravenous immunoglobulins). Treatment is given in stages. This therapy is mainly used in the case of a relapsing course of the disease.

Recent studies show that the prognosis of MS patients has improved. On average, it takes about 20 to 29 years before a patient is no longer able to walk a hundred meters without a walker. In former times this inability appeared already about 15 years. The improved prognosis is mainly due to the improved therapy options.

In general, it is very difficult to predict the course of the disease. However, it can be said that the first two to three years after diagnosis play a major role. People who have suffered many relapses with pronounced symptoms in the initial phase usually have a more severe course of the disease over a longer period of time than patients who have several years between relapses before a new relapse occurs.

In some cases, it can also happen that permanent symptoms disappear again. In such a case, the disease is called remission. In relapsing MS, remission often occurs within the first few years (secondary progressive MS). In the meantime, the following factors can be used to infer a favourable or unfavourable course of the disease:

Indications for a favorable MS- course:

• Female sex at birth
• Age of onset under 40 years
• Onset with only one symptom
• Onset with optic neuritis or with sensory symptoms (e.g. sensory disturbances)
• Complete recovery after the first episode
• Purely relapsing course
• Initially inconspicuous MRT
• Long interval between the first and second relapse
• Few relapses in the course
• Little disability a few years after MS onset

Indications for an unfavourable MS course:

• Male gender
• Age of onset over 40 years
• Onset with several symptoms
• The disease first manifests itself by balance disorders, or other disorders affecting the cerebellum or brainstem, as well as by a permanent reduction in strength or with bladder emptying disorders.
• No complete recovery after the first episode
• Chronic progressive course from the beginning
• Broad from the beginning numerous and characteristic changes in the MRI
• Small interval between first and second relapse
• Many relapses within the course of the disease
• Noticeable disabilities already a few years after MS onset

Some factors are known to have a negative influence on the course of the disease. These factors include infections, vaccinations, an accident, and major surgery. A stay in a warm climate, strong physical or psychological stress, as well as a fever can also have an unfavorable effect on the disease. Women who have just given birth suffer more often from relapses in the first months after the birth. A hot bath or rapid, deep breathing (hyperventilation) can cause a so-called pseudo flare-up. This is characterized by a drastic worsening of the symptoms, which, however, quickly and completely disappear.

Other triggers that can lead to a relapse, pseudo relapse or worsening of the symptoms are:

• Infections, especially viral infections (such as an influenza infection).
• Major operations
• Hormonal changes (such as puerperium)
• Some vaccinations, mainly with live vaccines
• Severe physical and psychological stresses
• Desensitization measures due to an allergy (=hyposensitization)
• Immunostimulatory drugs (this can also apply to herbal preparations)

Every second MS patient dies of complications of the disease in the advanced stage. These complications include, for example, kidney and lung inflammation (nephritis or pneumonia), severe kidney or lung failure (renal failure or pneumonal failure) or blood poisoning (sepsis). Some patients also suffer from severe depression and commit suicide for this reason. Others die from disabling accidents. About 50 percent of patients die from common causes of death that can also affect the healthy population, such as a heart attack, cancer, or stroke.

Multiple sclerosis mainly affects people between the ages of 20 and 40. Many sufferers are nevertheless able to continue working for years without any problems. Later, however, the disease can impair physical performance to such an extent that those affected are only able to carry out their profession in part or not at all.

Whether MS patients have a shorter life expectancy than healthy people depends on the respective form of the disease and the age of onset. People who develop MS at a young age have a life expectancy that is about six to seven years shorter than healthy people of the same age.