Multiple sclerosis

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system, with a lifetime prevalence of approximately 1 in 800. It typically presents between the ages of 20 and 40 and two-thirds of patients are female. Although the course is highly variable, MS is a progressive and incurable disease. It is responsible for a considerable burden of long-term neurological disability and is the most common chronic neurological disorder in young adults.

Demyelination

Axonal myelination is discussed in Chapter 5. The term demyelination refers to the loss of normally formed myelin and can be classified as primary or secondary:

Primary demyelination is selective loss of myelin with relative preservation of axons. Multiple sclerosis is the most common and important cause.

Secondary demyelination is degeneration of the myelin sheath following axonal loss.

It is important to distinguish demyelination (loss of structurally normal myelin) from dysmyelination in which the myelin sheath is not normally formed in the first place. Conditions characterized by dysmyelination are usually due to a metabolic abnormality or enzyme deficiency and are often inherited (Clinical Box 14.1).

Clinical Box 14.1: Leukodystrophies

The leukodystrophies are a large group of cerebral white matter diseases (Greek: leukos, white) caused by abnormal myelin formation in the brain and spinal cord. These conditions usually present in infancy or childhood with developmental delay or progressive neurological deterioration and there may be gradual regression of cognitive, language or motor abilities in a previously normal child. Neuroimaging confirms abnormal cerebral white matter. Most of the leukodystrophies are genetic in origin and may show a recessive, dominant or X-linked pattern of inheritance.

Key Points

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the CNS. It typically presents between the ages of 20 and 40 and two-thirds of patients are female.

MS is the most common and important cause of primary demyelination, which is characterized by loss of structurally normal myelin with relative preservation of axons.

Secondary demyelination is degeneration of the myelin sheath as a result of axonal loss. In dysmyelination (e.g. in the leukodystrophies) myelin formation is abnormal.

Clinical features of MS

Multiple sclerosis is usually a relapsing-remitting disorder. Each clinical episode (or relapse) is caused by a focus of demyelination in the brain or spinal cord, which is referred to as a plaque. When a relapse occurs, symptoms typically develop over a few days and gradually resolve over a number of weeks, as the inflammation subsides and the plaques remyelinate to a greater or lesser degree.

Common symptoms

Although plaques can occur anywhere in the brain or spinal cord, including the central visual pathways, some sites are more likely to be affected than others. This means that certain symptoms and signs are more common (Fig. 14.1). The most frequently encountered presenting features are weakness in one or more limbs (40% of cases) and optic neuritis (up to 25% of cases; discussed below).

Loss of vision

Inflammatory demyelination of the optic nerve (termed optic neuritis) is common in MS. This causes blurred vision in one eye, with reduced light and colour perception, combined with retrobulbar pain (discomfort behind the affected eye, exacerbated by movement). In some cases there is a blind spot or scotoma (Greek: scotos, darkness). Symptoms usually resolve completely within a few weeks, but there may be a persistent afferent pupillary defect (Clinical Box 14.2). Optic neuritis can occur as an isolated phenomenon, but 75% of affected individuals will eventually develop multiple sclerosis. Another common visual problem in MS is discussed in Clinical Box 14.3.

Clinical Box 14.2: Relative afferent pupillary defect

The pupillary light reflexes (see Ch. 3, Clinical Box 3.11) are often abnormal in patients with MS. Loss of myelin in the optic nerve may reduce the afferent drive to constrict the pupils when light is shone into the affected eye, causing a relative afferent pupillary defect (RAPD). This is demonstrated using the swinging light test. A pen torch shone into the normal eye causes strong constriction of both pupils. Quickly swinging the light across to the abnormal eye generates a weaker afferent drive to the pupil constrictor muscles (relative to the good eye) and both pupils paradoxically dilate slightly in response to the torch beam.

Clinical Box 14.3: Internuclear ophthalmoplegia