Multiple sclerosis I

Pathology

The pathological hallmark of MS is the plaque. This is an area of demyelination, with loss of myelin and relative preservation of axons (Fig. 1). Active lesions may have an associated inflammatory response and oedema. In more chronic lesions, the oedema and inflammation have resolved and there is a demarcated area of gliotic scarring, with atrophy and axonal loss.

Fig. 1 Myelin stain showing plaques.

Plaques can be found in any part of the white matter of the brain and spinal cord. There is a predilection for the periventricular white matter, the corpus callosum and optic nerves.

Pathophysiology

The area of demyelination disrupts the conduction of a nerve impulse (Fig. 2). This initially blocks conduction, but with recovery conduction is slowed and the refractory period is prolonged. Conduction along such segments is particularly sensitive to temperature changes and may fail if the temperature rises (which leads to Uhtoff’s phenomenon; see below).

Fig. 2 Effects of demyelination on an axon: saltatory conduction is blocked.

Pathogenesis

The aetiology of MS is unknown. There is a minor genetic component (the relative risk of a first-degree relative developing MS is two to four times that of the general population) and there is a tendency for an association with HLA antigens DR2 and DW2.

There is some geographical and racial variation in disease prevalence: lower rates are found in tropical countries and migrants from low-prevalence areas remain at low risk if they move over the age of 15 years; if younger, they take on the risk of their new home. The significance of these observations is not clear.

Investigation of an immunological basis for MS or an underlying viral infection have so far proved fruitless.

Clinical features

The peak age of onset of MS is 25–35 years. It is rare below 15 years and over 60 years. It is more frequent in women than men (about 1.5 : 1). There are essentially two patterns of disease (Fig. 3):

Fig. 3 Various patterns of progression in multiple sclerosis over time. (a) Relapsing remitting; (b) relapsing remitting to secondary progressive; (c) primary progressive.

Symptoms and signs

Visual

Optic neuritis is a common initial manifestation of MS. A visual disturbance evolves over a few days with distortion of the central vision and impairment of colour perception. There may be pain on eye movement. Visual loss can be mild to severe. Patients have a relative afferent pupillary defect and a central scotoma. The optic disc usually appears normal (retrobulbar optic neuritis) though may be swollen with papillitis. Vision improves over months, though may be incomplete, particularly if visual loss was severe initially. Optic atrophy may develop following an episode of optic neuritis (Fig. 4).

Fig. 4 Optic atrophy. Note pale discs.

Uhtoff’s phenomenon is the decrease in visual acuity following a rise in temperature, due to exercise, a hot bath or a fever.

Precipitating factors

Relapses occur more commonly after infections. There is a slight increase after trauma, though evidence is less clear-cut. There is a relative reduction during pregnancy with a slight increase afterward – over the whole period, the rate is stable.

Measuring disability

MS is a very variable disease. To try to assess treatment, it is imperative to have a reliable and valid measure of disability. This is straightforward for single components of disability, for example acuity and field, in assessing visual recovery after optic neuritis. A scale to cover the multiple possible disabilities found in MS will inevitably be less reliable: the most frequently used scale is the Kurtzke disability status scale (Box 1). This uses mobility as the major determinant. The scale is not linear (a one-point change means different things at different points on the scale) and has limited reliability. It is, however, the scale used in all recent major trials.

Multiple sclerosis I

MS is common, with a peak onset at 25–35 years of age.

MS is a disease of the CNS with multiple episodes of demyelination occurring at different times in different parts of the CNS.

The optic nerves, brain stem and spinal cord are the most commonly affected sites.