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Updated 12 February 2013

Multiple Sclerosis

Multiple sclerosis (MS) is a life-long chronic disease diagnosed primarily in young adults.

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Summary

  • Multiple sclerosis (MS) is a life-long chronic disease diagnosed primarily in young adults.
  • Symptoms of MS may be mild or severe and of long duration or short and appear in various combinations.
  • Doctors use a neurological examination and take a medical history when they suspect MS.
  • There is as yet no cure for MS.

Definition

Multiple sclerosis (MS) is a life-long chronic disease diagnosed primarily in young adults. During an MS attack, inflammation occurs in areas of the white matter of the central nervous system (nerve fibres that are the site of MS lesions) in random patches called plaques.

This process is followed by destruction of myelin, which insulates nerve cell fibres in the brain and spinal cord. Myelin facilitates the smooth, high-speed transmission of electrochemical messages between the brain, the spinal cord, and the rest of the body.

Symptoms

Symptoms of MS may be mild or severe and of long duration or short and appear in various combinations. The initial symptom of MS is often blurred or double vision, red-green colour distortion, or even blindness in one eye.

Most MS patients experience muscle weakness in their extremities and difficulty with coordination and balance. The majority of people with MS also exhibit paraesthesias, transitory abnormal sensory feeling such as numbness or "pins and needles". Some may experience pain or loss of feeling.

About half of people with MS experience cognitive impairments such as difficulties with concentration, attention, memory, and judgment. Such impairments are usually mild, rarely disabling, and intellectual and language abilities are generally spared.

Heat may cause temporary worsening of many MS symptoms.

Diagnosis and investigations

Magnetic resonance imaging (MRI) of the brain and spinal cord is the first-line investigation. It may show up multiple plaques and when compatible with the clinical picture, further investigations are often unnecessary. Cerebrospinal fluid (CSF) examination reveals immunoglobulin bands in about 80% of affected individuals indicating an immune response within the central nervous system (CNS).

Electrophysiological tests may provide evidence of previous lesion within the CNS in, for example, an undiagnosed and apparently solitary spinal cord lesion. Peripheral nerve studies are normal and EEG recordings are unhelpful.

Management and prognosis

Once diagnosed, practical decisions need to be taken about employment, home and plans for the future in the face of a potentially disabling disease for which there is no curative treatment.

There is no method of predicting the course of MS. Many MS patients continue to live self-sufficient productive lives while others are gravely disabled. In any chronic neurological disease, treatment of intercurrent infections is important. Urinary infections frequently exacerbate the symptoms.

Many forms of specific treatment have been suggested for MS, among them heat and cold therapy, radiotherapy, various vaccines, electrical stimulation, gluten-free diets, sunflower seed oil, asenicals and hyperbaric oxygen. None of these improve outcome.

The accepted treatment modalities of MS consist generally of drugs that alter or modify the immune system or elements of the immune response (immunological therapies) and those drugs that are used for the treatment of sequelae of demyelination, without immune alteration (symptomatic treatment). For practical purposes it is more convenient to consider the treatment of the various forms of MS separately.

Treatment of relapses

The treatment for an active relapse should consist of intravenous corticosteroids. At present a regime of 1000 mg IV methylprednisolane per day for three days followed by 1g/kg oral prednisone tapered over the next 11 days can be followed. The treatment does not cure the patient, but inhibits the inflammatory process and has tens recovery due to inhibition of inflammation. Oral corticosteroids have also been shown to be effective in the treatment of a relapse.

Treatment of Relapsing-Remitting MS (RRMS)

The aim of treatment for RRMS is to:

  • Reduce frequency of relapses
  • Decrease severity of a relapse
  • Delay or prevent onset of the secondary progressive phase

The treatment of RRMS consists presently of disease modifying immune-modulatory drug treatment.

The interferons, IFN-Beta-1a (Avonex ® and Rebif ®) and IFN-Beta-1b (Betaseron ®) are the mainstay of treatment of RRMS. These are different forms of recombinant IFN-Beta used in the treatment of MS. These different products are not considered to be interchangeable due to its different side effect profiles and dosage administration schedules.

Broadly spoken, the interferons have been shown to:

  • increase the time to the development of a second relapse in early MS;
  • reduce the frequency of relapses in RRMS;
  • slow the accumulation of physical disability in a four-year follow-up study.

However, it has not yet been shown to be cost effective in treatment of secondary progressive MS.

The interferons are administered either through weekly intramuscular injections (Avonex ®) or subcutaneous injections every second day (Betaseron ®). Rebif ® is administered subcutaneously three times weekly. It is still impossible to directly compare the different interferons’ efficacy with one another due to the lack of such studies.

Side-effects of treatment are many, with an acute flu-like illness occurring six to eight hours after the first injection. This usually disappears after subsequent injections. However, unwellness, headaches, muscle aches, depression, diarrhoea, hair loss and bone marrow problems commonly occur. Some of these unpleasant side-effects can be prevented or decreased by taking Paracetamol (Panado®) before the injection. Severe reactions occur infrequently, and include infection, severe depression, as well as cardiac and renal failure. The ß-Interferon is very expensive. Cost-benefit analyses are a source of serious concern, because the treatment is prolonged and expensive.

Glatiramer Acetate

Glatiramer acetate (Copaxone®) has recently been introduced and deserves further evaluation. It is a synthetic acetate salt that downregulates the inflammatory and auto immune responses associated with MS. It therefore has a different mechanism of action than the interferons and also a different side-effect profile as well as effect on MS disease activity.

Glatiramer acetate has been shown to reduce the frequency of relapses by approximately one-third. The daily administration route is subcutaneous. The drug is not associated with flu-like symptoms. It is generally well tolerated, but minor reactions like flushing, palpitations, dyspnoea and pain with erythema (redness) at injection site have been reported. Unfortunately, glatiramer acetate is like interferon also an expensive drug.

It seems that for those that can afford it, disease-modifying therapy should be initiated early in the disease course to prevent progression and possible sub clinical axon loss.

Other therapies used for Relapse-Remitting MS

In developing countries where cost is a major constraint, azathioprine (Imuran®) can be used as a form of maintenance therapy. Despite its potential harmful side-effect profile such as bone marrow suppression, it has been shown to be beneficial for patients with RRMS where relapses occur in a frequency of more than one per year.

Chronic treatment of RRMS with regular pulses of IV methylprednisdone was shown to decrease brain atrophy and T1-weighted black holes on MRI. A further study was recommended.

Treatment of Secondary Progressive MS (SPMS)

The aim of the treatment of SPMS is to slow the rate of worsening of the disease. Worsening of disease may be due to a combination of active inflammation with demyelination and/or axon loss and a progressive neurodegenerative process, which is not associated with inflammation.

There is some evidence that Interferon-Beta-1b may slow the progression of SPMS. There is still doubt, however, whether treatment with interferons is a cost-effective form of treatment of SPMS.

Mitoxantrone is an anti-neoplastic agent, which has been licensed in the United States to slow progression in patients with SPMS and worsening forms of RRMS. It has a lifetime-limited use of two to three years due to cummulative cardio toxicity.

Other older immunosuppressive drugs such as methotrexate and cyclophosphamide may also be used as a last resort for patients with severe progressive forms of MS.

Liason between medical practitioners, occupational therapists and social workers is mandatory and physiotherapy is of particular value in reducing the pain and discomfort of spasticity. Muscle relaxants such as baclofen (Lioresal®) or diazepam (Valium®) are also sometimes helpful. Prevention of pressure sores is vital.

Written by Prof Helmuth Reuter - FRCP (Edinburgh), FCP (SA), MMed (US), Department of Internal Medicine, University of Stellenbosch.

 
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