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MS information for health and social care professionals Neurophysiology

Myelin is a fatty substance, which coats the nerve axon and has an insulating effect enabling electrical impulses to move faster from the brain to the rest of the body and back again. People with MS have areas of damaged myelin that results in a disturbed transfer of information along the axons. In MS, the myelin sheath can be changed in two ways: the myelin itself may be damaged or there are patches of inflammation in the myelin. If the inflammation covers a wide area it can leave a scar (sclerosis) in the CNS, also referred to as a lesion. These lesions can appear in many sites throughout the CNS - hence 'multiple'.

There is also an increasing body of evidence that the axons themselves become damaged and that axonal loss is a cause of impairment. Once lost an axon can never regenerate and this is thought to account for the progressive disability which is often part of the condition. Axonal loss is now believed to occur much earlier in the disease process than was once thought.

MS can affect any part of the CNS and can potentially affect movement and muscle activity at several different sites, giving rise to a variety of physical and sometimes cognitive symptoms, in addition to the psychosocial problems that can also result.

Onset

Onset of MS rarely occurs before puberty and is usually in early adult life. The incidence of onset rises during the 20s, reaching its peak in the late 20s and early 30s. The onset of the disease is often monosymptomatic, with evidence of a single lesion of the CNS in 45% of cases. However, there may be symptoms indicating multiple lesions from onset. Initial symptoms are, most commonly, visual disturbances, including pain in and around the eyes, blurred or double vision, and sensory problems that take the form of 'pins and needles' in the hands and feet. Symptoms vary enormously, not only from one person to another, but also in the same person from one time of day to another.

Diagnosis

MS is difficult to diagnose since there is no single test, or clinical feature which is exclusive to the condition, and so other possible causes must be eliminated. A diagnosis of definite MS is based upon objective evidence of lesions separated in time and space, ie relapsing and remitting symptoms affecting at least two separate areas of the brain or spinal cord. Confirmation of the condition can therefore take some time.

There are established criteria that have to be met to positively identify MS. These are known as the 'McDonald Criteria' and are relevant in diagnosis of both relapsing remitting and primary progressive MS[1]. Revision of these criteria in 2005[2] allows for earlier diagnosis of MS without any loss of accuracy. This facilitates earlier use of disease modifying drugs that may have an impact on later accumulation of disability for people experiencing relapses.

NICE guidance[3] states that the individual should be involved in the diagnostic process and should be informed as soon as a diagnosis of MS is considered reasonably likely. In a study of patient satisfaction and timing of diagnosis patients themselves preferred early diagnosis[4].

The typical diagnostic process - GP refers person to neurologist who takes a detailed history and conducts a physical examination. Further investigations involve CSF MRI and Neurophysiology

The typical diagnostic process

A critical element in the diagnostic process recognised by NICE is around information giving. The healthcare professional should find out how much and what information the individual wants to receive. Explanations of diagnostic tests should be given. The importance of patient information in the management of MS is further highlighted in the recommendation that:
son 'People with MS should be enabled to play an active part in making informed decisions in all aspects of their MS healthcare by being given relevant and accurate information about each choice and decision'.

Appendix E of the Guideline details principles of good communication. Research into the information needs of people who have MS also makes recommendations about how information should be delivered[5].

Clinical evidence

A thorough physical examination of the current function of the nervous system is made. Specifically, signs of weakness or stiffness in the limbs and areas of abnormal/reduced sensitivity on the body surface will be looked for. Evidence of current or previous damage in the optic nerve is important (and can be detected through an ophthalmoscope) as this is a common site of lesions in MS. However, it is becoming less common to make a certain diagnosis of MS on clinical evidence alone, since in many cases such evidence is subjective.

Diagnostic tests

There are three major investigations, all or some of which may be carried out when MS is suspected though none are 100% conclusive without supporting clinical evidence.

  • Magnetic resonance imaging
  • Neurophysiological tests
  • Examination of CSF (Cerebrospinal Fluid)

Magnetic resonance imaging (MRI)

MRI is the most sensitive investigation, superseding previous scanning methods due to its superior resolution and ability to highlight areas of active and non-active demyelination. MRI uses the magnetic properties of hydrogen atoms in the body to create crosssectional images. Unlike CT scans which measure density in body tissues, MRI measures water content in different parts of the brain. The water content in an area of demyelination is very different from that in the surrounding areas. The use of an enhancing agent, such as gadolinium, will show whether a lesion is active or not. In active inflammatory lesions the blood-brain barrier is disrupted and the gadolinium leaks into the surrounding brain tissue and can be detected on the MRI image.

Further developments in this area include magnetic resonance spectroscopy and magnetisation transfer imaging. However, there are still problems in establishing a correlation between the lesions as revealed by MRI and the clinical presentation.

Neurologists use MRI for the following purposes:

  • To observe abnormalities that are suggestive of multiple sclerosis
  • To rule out alternative diagnoses such as tumours or stroke
  • To help in the evaluation of patients who have subjective complaints but few objective signs of abnormality
  • As a surrogate marker for disease activity in clinical trials

Neurophysiological tests

These relatively simple, non-invasive investigations are carried out on vision, hearing or sensation to look specifically for delay in the conduction of nerve impulses to and from the brain.

The most common test is the visual evoked potential (VEP). Visual tests involve watching a television screen that has alternating black and white squares. An electrode is placed over the visual cortex and a computer analyses the received visual signal from the television set. The length of time it takes for the signal to leave the television set and reach the visual cortex is known and thus a delay in the signal transmission can be identified. Such a delay may be indicative of damage due to an MS lesion.

CSF examination

Examination of the cerebrospinal fluid (CSF) used to be an important diagnostic aid but the increased use of MRI has reduced the need for this invasive procedure. Fluid is drawn off the spinal cord by means of a lumbar puncture. NICE guidance states that this should only be used when the situation is clinically uncertain; however it is still of importance in the diagnosis of primary progressive MS.

The sample of CSF is analysed by electrophoresis for its protein level and leucocyte count. Approximately 80% of people with MS have an elevated IgG index or oligoclonal immunoglobulin bands present in the spinal fluid but not in the serum, indicating inflammation and immunological disturbance.

References

  1. McDonald WI, Compston A, Edan G et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on Diagnosis of Multiple Sclerosis. Ann Neurol 2001;50(1);121-27.
  2. Polman CH, Reingold SC, Edan G et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald criteria". Ann Neurol 2005;58(6):840-46.
  3. National Institute for Clinical Excellence. Multiple Sclerosis - Management of Multiple sclerosis in Primary and Secondary Care. NICE Clinical Guideline 8. London:NICE; 2003.
  4. Janssens ACJW, de Boer JB, Kalkers NF et al. Patients with multiple sclerosis prefer early diagnosis. Eur J Neurol 2004;11:335- 37.
  5. Box V, Hepworth M, Harrison J. Identifying the information needs of people with multiple sclerosis. Nurs Times 2003;99(49):32-36.