Differential Diagnostic Considerations for Multiple Sclerosis
Diagnosing MS is equivalent to a heavy stroke of fate. The term MS is widespread nowadays and the idea that many people have of this disease often entails a life of disability. It is thus all the more crucial to ensure an accurate diagnosis. The following differential diagnostic points should thus be considered:
Treating Multiple Sclerosis
The treatment objectives of MS include prevention or reduction of new manifestations, hindering progression of the disease, halting activity of the disease, improvement of symptoms and improvement of quality of life. A broad regime of treatments is available to achieve this, and it is divided into three pillars:
1. Treating the Acute Manifestation of MS
The treatment of choice for the acute inflammatory manifestation includes intravenous administration of methylprednisolone over 3 – 5 days. 1000 mg are applied each morningwith additional gastric protection (proton pump inhibitor) and thrombosis prevention. Clinically, blood sugar and blood pressure should be checked regularly. Should the symptoms not nominally improve, the treatment may be extended to up to 2000 mg methylprednisolone IV over 5 days, or plasma separation may be discussed.
2. Immunomodulatory Treatment of MS
One must choose carefully when to commence preventative, long-term treatment. A paradigm shift occurred a few years ago, and now the recommendation of long-term early treatment is ubiquitous. The BENEFIT study revealed a delay in progression of the disease by about 580 days, when the treatment had already commenced by the time of diagnosis. The basic therapy is initially differentiated from the escalation of treatment. Interferon compounds and glatiramer acetate are primarily available as basic therapeutic agents.
- Interferon beta: Endogenous cytokine, s.c. or i.m. administration, side effects: Fever-like symptoms at start of treatment, skin irritations, increased liver function readings; in some cases, neutralizing antibodies are produced that undermine effectiveness accordingly.
- GLATiramer acetate: Peptide mixture of glutamate, lysine, alanine and tyrosine in identical molar ratios as a myelin protein, daily s.c. administration, well tolerated
However, should this result in greater disease activity with multiple (severe) manifestations within a year despite basic treatment, a treatment escalation should be done to expand the treatment. Natalizumab, mitoxantrone and fingolimod are permitted. These pharmaceuticals are all known for their strong efficacy, yet have a wider range of side effects than the basic therapeutics.
- Natalizumab: Recombinant humanized monoclonal antibody to inhibit lymphocyte transmigration via the blood-brain barrier, intravenous administration every 4 weeks, generally well tolerated, but: risk of PML (= progressive multifocal leukoencephalopathy) of 1:1000 with high mortality and lethality
- Mitoxantrone: Cytostatic agent, cytotoxic for lymphocytes and macrophages, intravenous administration every 3 months, relevant side effect: cumulative cardiotoxicity, increased risk of leukemia, infections; mitoxantrone is also permitted for secondary progredient MS
- Fingolimode: Daily oral ingestion, prevents the migration of lymphocytes into inflamed target tissue, side effects: infections, liver damage, macular edema, cardiac arrhythmias
Recent developments: Along with these known pharmaceuticals, there have been some recent developments in pharmaceutical treatment over the past few years.
Dimethyl fumarate is a new basic oral therapeutic agent. When treatment commences, gastrointestinal intolerance and flush phenomena often set in. Regular check-ups of the differential hemogram should be conducted even during long-term administration in order to avoid opportunistic infections.
A highly active, monoclonal antibody for the treatment of MS has recently been introduced with alemtuzumab. Originally used for T-cell lymphoma, alemtuzumab leads to sustainable elimination of T- and B-cell sections of the immune system over a span of months. The advantages are treatment cycles with 5 or 3 infusions in the 1st or 2nd year, and possibly in the 3rd year, as well as a very positive effect on MS activity in many patients.
The disadvantages are a slight increase in vulnerability to infection during the months after infusion, and the development of secondary, B-cell-transmitted auto-immunity phenomena or diseases (formation of autoantibodies, ITP (M. Werlhof) and glomerulonephritis). This requires 48-month lab and urinary tests in a 4-week cycle after the last administration of alemtuzumab.
The DGN (German Neurological Society) also recommends the administration of rituximab as a basic therapy when treating neuromyelitis optica (NMO). Retrospective data showed that rituximab is highly effective and tolerable, even over a longer period of time. The administration of MS-specific therapeutics (especially interferons, fingolimode, natalizumab) should be avoided, as these have been shown to have deteriorating effects.
3. Symptomatic Treatment Options of MS
Along with the therapeutic measures for treating or preventing an inflammatory manifestation, many other therapeutic approaches are taken for MS that are determined by the location of the neuronal damage (and corresponding symptoms).
Overall, many MS patients benefit from physical and physiotherapeutic measures, as well as sports, yoga, speech therapy and ergotherapy. The following table provides a brief overview of the accompanying symptoms of MS and the ways in which they can be treated:
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