Multiple Sclerosis

What is multiple sclerosis?

Multiple sclerosis (MS) affects the function of the brain, spinal cord and nerves. It is caused by inflammation and destruction of myelin in small patches called plaques. Myelin is a white fatty tissue that surrounds nerve fibres and insulates them against short-circuits that can prevent nerve signals from having their desired effects. The "demyelination" process interferes with nerve impulse transmission, causing a wide variety of symptoms affecting sensation, movement and thought. Myelin damage occurs in attacks that usually resolve with time, allowing symptoms to subside, but repeated demyelination can damage the nerve fibres resulting in progressive and persistent disability.

MS is an autoimmune process thought to be triggered by a virus or environmental factors in those with a genetic predisposition. Typically MS is first diagnosed when individuals are between 20 and 50 years of age, although it can occur in young children. It affects women two or three times more often than men, is more common in Northern European Caucasians than other ethnic groups and is seen in greater numbers in people who live in temperate climates than warm ones. Between 2 and 2.5 million people are affected worldwide with about 100,000 in the UK. The risk of developing the disease is estimated to be about 1 in 750 in the general population. In families with an affected member the risk rises to 1 in 40, and it is about 1 in 4 for the identical twin of an affected person, strengthening the notion of a genetic predisposition.

There is no single test that can conclusively diagnose MS. Instead, doctors will consider a patient's medical and family history together with a variety of clinical and laboratory tests to aid diagnosis. In 2001 an international panel chaired by Dr Ian McDonald recommended that to diagnose MS a doctor must:

  • Determine that the central nervous system has been damaged in at least two places
  • Confirm that the damage occurred at separate times, more than one month apart
  • Rule out other conditions that cause a similar set of signs and symptoms

The McDonald criteria have been regularly updated to include radiological and laboratory tests that can help to make a more rapid diagnosis, for example following a single attack.

Once diagnosed, an individual may be classified as having one of several types of MS based on signs and symptoms, frequency of relapses, rate of disease progression and the number of areas of the central nervous system that are damaged.

Signs and Symptoms

Because MS can attack any area of the central nervous system the signs and symptoms are many and varied. Symptoms of MS may come and go, and they may last from days to months. They include:

  • Sensory symptoms such as numbness, tingling, pain, burning, itching, facial pain and visual disturbances
  • Motor symptoms such as speech impediments, weakness, tremor, difficulty walking, lack of coordination, constipation and problems with the control of urination
  • Psychological symptoms such as mood swings, depression and problems with thinking, learning and memory
  • Fatigue (occurs in up to 90% of those with MS)
  • Temperature sensitivity (occurs in up to 60%; symptoms temporarily worsen with heat)

About 80% of those with MS have the relapsing-remitting type (RRMS) at the time of diagnosis. They experience periodic attacks or relapses followed by healing and symptom remission which may or may not leave residual disability. Later in the course of the disease about half develop secondary progressive MS (SPMS). Their symptoms and disabilities worsen as they continue to have relapses but do not fully recover. About 10% of people with MS have a primary progressive form of the disease (PPMS). They grow gradually worse without experiencing remissions.

Tests

Although there is no single test or set of tests that can establish a diagnosis of MS, there are three tests that are generally considered useful:

  • Cerebrospinal fluid (CSF) analysis
  • Evoked potentials (EP)
  • Magnetic resonance imaging (MRI)

Laboratory tests

There are no laboratory tests that are completely specific for MS, but several are helpful in diagnosing or excluding this disease as the cause of signs and symptoms. The most useful tests look for evidence of immunoglobulin G (IgG) production within the central nervous system.

CSF Electrophoresis and Isoelectric Focusing
Electrophoresis and isoelectric focusing are two methods for separating the proteins in a biological fluid. A patient's CSF and serum are evaluated side-by-side on a test surface using either of these techniques. Following the separation step, a protein stain is applied to both specimens and the banding patterns that appear in the CSF and serum are compared. The presence of two or more IgG bands in CSF that are not present in serum is a positive test for oligoclonal banding. About 90% of those with MS show permanent oligoclonal banding in their CSF.

CSF Immunoglobulin G (IgG) Index
Increased levels of CSF IgG can be due to excess production of IgG within the central nervous system, and is seen in MS and several other diseases. It can also be due to leakage of plasma proteins into the CSF that can occur with inflammation or trauma. To discriminate between these two possibilities, the IgG index is calculated from IgG and albumin measurements in CSF and serum:

IgG index = (CSF IgG / serum IgG) / (CSF albumin / serum albumin)

An elevated IgG index indicates increased production of IgG within the central nervous system. It is found in about 90% of MS cases.

Myelin basic protein
This protein is a major component of myelin. Increased concentrations of myelin basic protein in CSF indicate that demyelination is taking place. This process is not specific for MS because other inflammatory diseases of the central nervous system can also elevate the amount of myelin basic protein in CSF. The test may be used to assess disease activity in established MS but is not widely available.

Doctors may also test for diseases that can cause symptoms similar to MS to determine if they may be responsible for a patient's illness. Examples include:

  • Autoimmune disorders (e.g. lupus)
  • HIV
  • Lyme disease
  • Sarcoidosis
  • Syphilis
  • Vasculitis
  • Vitamin B12 deficiency

Non-laboratory tests

The Evoked Potentials test involves measuring the time it takes for the brain to receive messages by placing small electrodes on the head to monitor the brain wave response to what is seen or heard. Damage to myelin can slow nervous system response time and the tests can reveal evidence of damage along nerve pathways.

An MRI (magnetic resonance imaging) scanner uses a strong magnetic field to create a detailed image of the brain and spinal cord. It is very accurate and can show the exact location and size of both permanent scarring and new lesions. MRI scans confirm the diagnosis in over 90% of people with MS.

Treatment

There is no cure for MS. It does not significantly decrease lifespan, but it can frequently and intermittently affect quality of life. The goals of MS treatment are to slow the progression of the disease, relieve symptoms and minimise the effects of acute attacks.

Doctors may prescribe corticosteroids for short periods of time to speed recovery from relapses and other drugs to address specific symptoms. Details of the drugs that are used as well as information about the multidisciplinary support provided by the NHS for patients with MS can be found in the web sites listed under Elsewhere On The Web.