The Multiple Sclerosis (MS, also Disseminated encephalomyelitis) is an inflammatory / demyelinating and degenerative disease of the central nervous system and epilepsy after the second neurological disease of younger adults.

Two essential features characterize the disease. First, enter the brain and partially dispersed in the spinal cord inflammation, which attack the body’s own immune cells to the myelin sheaths of the nerves caused. Furthermore, it is for various reasons (see 4.2) to a cellular damage to the axons. These developments are in the course of the disease to a decreased conductivity of the nerves, making the typical symptoms such as tingling; spasticity, paralysis, rapid fatigability (fatigue), and visual disturbances are triggered.

Contrary to popular belief, MS does not necessarily lead to severe disabilities. 15 years after the beginning of illness (without treatment) for at least 50% of all patients still walk. Multiple sclerosis is not contagious and rarely fatal. Less than 10% of MS patients die from the direct consequences of the disease or its complications.

Epidemiology

The Multiple Sclerosis is the most common in Central autoimmune inflammatory disease of the central nervous system. The first symptoms usually occur in young people between 15 and 40 Year of life, but these often remain undetected. Women are affected twice as often as men are. Estimates for Some parts of the world showed about 100,000, (approximately 70 per 100,000 population) (Source: DMSG), in Austria around 8500 patients, with estimates of the number of sufferers in Some parts of the world from about 67,000 to about 138,000 range. The high dispersion is due to the alleged high number of sufferers are not diagnosed.

In the equatorial zone there is less MS disease than in the northern or southern latitudes. Through immigration studies could be shown that this is only for people, who in early childhood moved so that the MS as a late consequence of early infectious disease is discussed. Directly transferable to non-MS, as the basis of studies with adoptive children could be detected.

According to a study by Anne-Louise Ponsonby at the Australian National University in Canberra is likely to be diagnosed with MS, the lower, and the longer one with siblings together. If you have more than five years of contact with siblings, the risk is reduced by about 90 percent. The scientist explained that through the mutual contagion of siblings with infectious diseases, which generally protects against autoimmune diseases.

Genetics

The MS is not a classic genetic disease. Currently, it is caused by a combination of genetic predisposition and external factors. The factors of MS are polygenic characteristics, ie, only several genes together increase the disease risk.

Two studies conducted in Canada and Britain have been carried out, show the following picture for the disease probability in dependence of the degree of relatedness:
Relationship risk
In the population about 0.2%
Related 1st grades about 3%
Related 2nd grades about 1%
Related 3rd Grades approximately 0.9%
Twins about 35%
Siblings about 4%

Forms

It is among several forms are distinguished:

* Relapsing remitting MS
* Primary progressive MS
* Secondary progressive MS
* Brilliant ends MS (rare)

While the inflammation in the relapsing course may occur in acute phases and after resolution of inflammation at least in part, the symptoms disappear, the amplification of symptoms during primary and secondary progressive course of creeping slowly in fulminant type continuously and very rapidly in front of him.

A further division by Lassmann et al. in 2001 defines and distinguishes the Demyelinisierungsmuster of the lesions in the CNS. A determination of the Läsionstyp could lead to a specific, effective therapy, but is currently only supported by a biopsy of the brain possible.

Type of immuno logical mechanism

1 macrophage-mediated T cell mediated inflammation with activation of macrophages and microglia cells.
2 antibody-mediated as 1, only with the involvement of complement
3 Distal Oligodendrogliopathie T cell-mediated vasculitis of small vessels and ischemic injury of white matter
4. 3, with secondary demyelination as 1 additional oligodendrocytes are metabolically injured

Pathophysiology

Damage to the myelin layer

The pathogenesis of MS is unclear. It is now, however, that it is an autoimmune disease against myelin coating of nerve cells of the central nervous system involved. This is also an animal model: mice, where the myelin basic protein injected, develop an Experimental Autoimmune Encephalopathy (EAE), the MS in humans is very similar. It was shown that special cells of the immune system, namely CD4 + Th1 cells (T helper cells), the blood-brain barrier to overcome, and in the central nervous system (CNS) to immigrate. The now activated CD4 cells pour messengers (cytokines) from the inflammation and immunreaktionsfördernde effect. These messengers include mainly gamma interferon (IFNy) and interleukin-2 (IL-2). In this way they call an inflammatory reaction against the supporting tissue of the brain (glial cells) and their nerve cell sheath (myelin) to highlight and promote its degradation. It comes with the test from the typical symptoms of the disease.

Experimental data suggest that injured nerve fibers are already at least partially recovering their conductivity can, by increasing sodium channels in the cell expressing.

Injury to the axons

With modern imaging techniques such as MRI has made in recent years become possible to demonstrate that the impairment of the axons, if not the decisive factor in the development of permanent disabilities. These studies show that this damage not only in chronic forms or late stages of relapsing MS to happen, but from the outset, are involved. The sinking of the axons also covers areas of the brain where the myelin layer is still fully intact and seems so from the T-cell response against myelin independent.

The mechanisms leading to this type of damage are not yet fully understood. Currently, it seems as if a defective regulation of the brain messenger substance glutamate and increased release of nitric oxide (NO) play an important role. Another aspect could also be the direct destruction of axons by autos reactive CD8 T-cells.

Recent research findings (2006) suggest that B-cell antibodies to the enzymes GAPDH and TPI bind and thus deactivate the enzymes for the degradation of the axons are at least partly responsible. A reduced availability of GAPDH, in the mitochondria of the axons that less of the cellular energy source ATP is produced. This can potentially supply to the downfall of the axon lead. It is also known that a lack of TPI may result on neuro-degenerative disorders.

Animal experiments, in which drugs for the accelerated degradation of glutamate (in the brain) were used, showed a significant reduction in axonal damage.

Diagnosis

Since the analysis of symptoms occurring frequently no definite diagnosis is permitted, additional neurological and radiological studies:

* Neurological examinations
* Evoked potentials, a deceleration of the latency is here on a disturbed conduction in nerve out with advanced MS can also lead to a deformity, reduction or loss of potential come.
* EEG
* Investigation of the cerebrospinal fluid, the liquor is 90% of pathologically altered and it is suspected to be a lumbar puncture.
+ Plasma cell proliferation (lymphocytic Pleozytose)
+ Protein propagation; monoclonal IgG production, so-called “oligoclonal IgG bands (differential diagnoses: SSPE; Lues; Virusencephalitiden)

* Radiological investigations
* Magnetic resonance imaging; in the extra layer images of the brain can be healed and inflamed tissue areas are presented as well as with the help of contrast agents (gadolinium) acute outbreaks can be observed.
* Only rarely is the computed tomography, because the visualization of inflammation using magnetic resonance imaging better is possible.
* Chemical Laboratory Investigation
* Determination of anti-MOG antibodies and anti-MBP antibodies

After diagnosis, the disease with ICD-10 code G35 encrypted.

Therapy

Although a cure for multiple sclerosis has not yet possible, some medications are available, the course of MS to slow down and have already occurred may relieve symptoms.

Long-term therapy

The development of long-term therapy is based on the assumption that is to MS is an autoimmune disease. The agents try Immune suppression by (suppressing the immune system) or immune modulation (change of the immune response) in the disease Done to intervene. One difficulty with this Wirkprizip is that an unspecified change in the immune system to a higher infectious disease and cancer rates can lead to.

Due to the available drugs, the following therapeutic successes achieved by the slow progression of disability and improve quality of life of patients:

* Reducing the shear rate
* Lost less severe relapses.
* Protection from axonal and neuronal damage

The following drugs are currently available:

Drug brand name publications
Azathioprine Imurek
Glatiramer acetate Copaxone
Interferons Betaferon ®, Avonex ®, Rebif ®
Antegren Natalizumab Tysabri ® = ®
Mitoxantrone Ralenova ®
Cyclophosphamide Endoxan ®
Methotrexate 7.5 METEX ®
Immunoglobulin Gamunex ® 10%

Therapy of acute relapses

Under the administration of high doses of cortisone can be used during the relapse of acute inflammatory response within the shortest possible time to close. The infusion doses are – depending on the seriousness of the thrust and the constitution of the patient – usually:

1x each day:

* 5 days on 500 mg prednisolone
* 3 days or 1000 mg prednisolone
* 5 days or 1000 mg prednisolone
* 5 days or 2000 mg prednisolone (in very severe cases).

Since Corticoid very well from the gastrointestinal tract is absorbed, the Kortisongabe also in tablet form and in about three weeks, while the daily dose is reduced gradually (‘tapering’). If after the tapering the impact of a relapse is still felt, should the recent recommendation of the Society for Multiple Sclerosis, second cortisone Pulstherapie with a double dose to be carried out. However, there is now no studies suggested indications that the long-term course of the disease by Corticoid would be positively influenced. A very high and long – especially in severe relapses often necessary – cortisone treatment is often associated with eminent körperschwächenden side effects.

Symptomatic therapy

In the course of MS are often symptoms in-patients who do not cause can be treated, but their occurrence by different drugs can be mitigated. The main complaints about this with some common medications are listed below:
Drug brand name remark
Treatment of chronic neuropathic pain
Carbamazepine eg Tegretal ®
Oxcarbazepin Trileptal ®
Gabapentin Neurontin ®
Chronic fatigue and energy (fatigue syndrome)
Acetyl L-Carnitine 1000 mg 1x daily
Amantadine PK-Merz ®
Gabapentin Neurontin ®
4-Aminopyridin just as pure substance to studies runs
Modafinil Vigil ®
Pemolin Tradon ®
Painful muscle stiffness (spasticity)
Baclofen (intrathecal) e.g. Lioresal ®
Tizanidin Sirdalud ®
Buprenorphine Temgesic ® / Subutex ®
Muscle trembling (tremor)
Isoniazid eg Isozid ®

Deep brain stimulation implantation of a stimulation electrode in the thalamus

Alternative Therapy

Below are discussed some alternative methods for the treatments of MS are listed. It must be mentioned that none of them sufficiently scientifically been studied and therefore no conclusions about their effectiveness can be taken. Even with the alternative therapies can cause significant side effects and the cost of this therapy are generally not covered by health insurance.

Treatment sources
Amalgam removal (PDF)
Green tea extract EGCG
Omega-3-fatty acid (eg Lachsölkapseln)
Prevention of omega-6-fatty acid
Vitamin B12
Cannabis products
Immune therapy (eg Colibiogen)
Hyperbaric oxygen therapy]
Uncaria tomentosa – Cat’s Claw
Homeopathy
Weihrauch
Traditional Chinese Medicine
Macrobiotics
Ruta tea
Grimace diet
Calcium EAP
Electro Magnetic Field Therapy
Inosine
Nemexin or LDN

Views

Long-term immuno modulatory and neuro protective therapy
Active ingredient (brand name) status sources
Statins Phase III studies running
Combination of interferon and glatiramer acetate trial runs
Combination of glatiramer acetate and mitoxantrone Small study successfully Combination of interferon with cortisone shock therapy Initial studies successfully
Daclizumab (Zenapax ®) (an IL2 inhibitor) Major Phase II trial runs
Alemtuzumab (Campath ®) (an anti CD-52 antibody) Phase II is successful, Phase III in planning
Rituximab (Rituxan ®) Phase II is successful, Phase III runs
Nogo A animal studies, clinical start in about 2 years
Oral Cladribine (Mylinax ®) Phase III trial runs]
Aimspro (Caprivax ®) serum from goats Phase II trial runs
MBP8298 phase III trial runs
FTY-720 (Fingolimod ®) Phase III trial runs
Laquinimod Phase II study successfully completed
Teraflunomide phase III trial runs
CCR1 antagonist ZK811752 tablets phase II trial is nearing completion
MN-166 tablets phosphodiesterase IV inhibitor Phase II trial runs
Tovaxin T cell vaccine Phase-I/II-Studie successful, Phase II / III trial starts 2006
NeuroVax T-cell vaccination Phase-I/II-Studie runs
Pirfenidone Phase II study successfully
BG-12 Phase II study successfully
Inhibitors against e.g. Glutamate or free radicals unknown
Trichuris Sui’s ova trial runs at the Charité

Symptomatic therapy

Symptoms of drug status
4-Aminopyridin ® Fampridin increase conductivity of the nerve to run trials.
Cannabis spasticity, sleep disturbances are running trials.

Remyelinisierung

The aim of the Remyelinisierung is already damage in MS patients by a reconstruction of the myelin layer repair.

Forecast

So far, at the beginning of the disease hardly possible to make a prediction about the future course to what the patient very burdened. The symptoms of the disease are varied art is called multiple sclerosis therefore ‘the disease with a thousand faces “. One way to predict the disease course could be the determination of bio-markers such as the anti-MOG antibodies and anti-MBP antibodies offer – see Multiple sclerosis (studies).

Recent studies employed globally in terms of the nucleus accumbens presented at a potienziell a priori (= anticipated anamnesis) diagnosed with MS 70% (test series with 320 people on suspicion of MS) strongly degenerated constellation of dopaminergic system and its messenger budget. The background to this investigation, however, was a genetic positive correlation with general dependence Formulation of the general mechanisms in the brain demonstrated.

In recent years there have been some relatively large-scale studies on the course of multiple sclerosis performed. The results were mostly positive, and surprisingly showed that the course of the disease was much milder than assumed.

It should be noted that these investigations no predictions regarding an individual permit, but only of statistical significance. In addition, this is carried out to certain groups or certain geographic areas based, so not necessarily by the outcome of the situation in other geographical areas or population groups can be closed.

Other descriptions of the disease

* Disseminated encephalomyelitis – disseminated encephalomyelitis-demyelinating demyelinating encephalomyelitis – Entmarkungs-encephalomyelitis – Polysklerose – Sclerosis multiplex – Sclerose en Plaques disseminée – CHARCOT1 Disease