Multiple sclerosis

Multiple sclerosis

Definition

An immune-mediated disease characterised by discrete areas of demyelination in the brain and spinal cord.

Incidence/prevalence

About 60 per 100,000 in England.

Age

Peak onset is between the ages of 25 and 40 years, uncommonly presents over the age of 60.

Sex

Women slightly more than men (1.7:1).

Aetiology

There are several factors postulated.

·        It is thought that there is an abnormal immune response, possibly triggered by an unknown viral antigen.

·        Genetic predisposition to the disease – monozygotic twins have a 20–40% concordance, whereas siblings and dizygotic twins have a 3–5% risk.

·        There is an association with HLA-A3, B7, DR2 and DR3.

·        Childhood exposure to some environmental factor – migration before the age of 15 years leads to the risk of MS becoming that of the new country.

Pathophysiology

Discrete areas of demyelination called ‘plaques’ ranging in size from a few millimetres to a few centimetres. They are often perivenous and common sites in the brain include the optic nerve, around the lateral ventricles and in the brainstem and cerebellar peduncles. The cervical spinal cord is also commonly affected, but any part of the central white matter may be involved. The myelin of the peripheral nerves is not affected.

Initial oedema around the soft patches of white matter leads to symptoms that partially resolve as the oedema subsides.

The areas of demyelination are disseminated in time and place.

Clinical features

There are several patterns of the course of MS.

·        Relapsing-remitting MS affects about 20–30% of patients, with lesions (and symptoms and signs) affecting different areas of the CNS at different times, with full or partial recovery between episodes, but no progression between.

·        Primary-progressive MS affects 10–20% (particularly older patients), the pattern is that of chronic progressive deterioration from the time of onset.

·        Secondary-progressive MS (about 40%) when the initial onset is of relapsing-remitting, then after several years this becomes a chronic progressive form of the disease.

Examples of clinical features include the following:

Optic neuritis – usually unilateral visual loss which progresses over days, which may be mild or severe. Pain in or behind the eye, exacerbated by movement, is common. On examination there is loss of visual acuity and colour vision, a central scotoma and fundoscopy may demonstrate a swollen optic disc (in retrobulbar neuritis, where the optic nerve is affected, the disc looks normal). In an initial presentation of unilateral optic neuritis, only about half of patients will go on to develop MS.

There may be motor, sensory, bladder, bowel or sexual disturbances. There may be hemiparesis, paraparesis or monoparesis. On examination, upper motor neurone signs are found (i.e. increased tone, pyramidal distribution of weakness, brisk reflexes, upgoing plantars and loss of abdominal reflexes).

Lhermitte’s phenomenon is suggestive of MS – lightning like pains going down into the spine or limbs which occurs on neck flexion.

Visual disturbances such as diplopia due to VIth nerve palsy or internuclear ophthalmoplegia. Internuclear ophthalmoplegia is a horizontal gaze palsy resulting from a lesion affecting the medial longitudinal fasciculus (MLF) in the brainstem or pons. When a patient attempts lateral gaze there is an inability to adduct the eye which is ipsilateral to the MLF lesion and the contralateral eye fully abducts but with nystagmus.

Cerebrellar involvement may also cause other cerebellar signs may occur.

Depression and intellectual impairment are common in longstanding MS, especially with widespread cerebral hemisphere involvement.

The diagnosis may be made clinically if there are two or more attacks separated in time with, clinical evidence of lesions in different areas. Following a single attack or clinical evidence of only one lesion area the diagnosis may still be made if there is radiological evidence of two or more lesions in time or space (McDonald Criteria).

Microscopy

Loss of myelin associated with lymphocytic cuffing of small vessels. In fresh lesions, increased numbers of macrophages phagocytose the damaged myelin and form foam cells. Old lesions are firm, grey-pink ‘burnt-out plaques’ that have very few inflammatory cells and are dominated by astrocytes.

Investigations

MRI brain and spinal cord shows increased intensity lesions on T2-weighted images, gadolinium will cause enhancement of an acute lesion on T1-weighted images.

CSF shows oligoclonal bands of IgG only within the CNS (i.e. not found in serum). This test is only positive

in ∼90% and false positives can occur.

Electrophysiological tests: visual brainstem, somatosensory and auditory evoked responses may demonstrate previously subclinical lesions.

Management

Supportive management and counselling, physiotherapy as indicated. Bladder symptoms, muscle spasms, pain and other problems are treated appropriately.

·        Short course, high-dose oral or intravenous steroids are used in acute relapses. These cause more rapid improvement, but do not appear to reduce the residual neurological deficit. They are therefore usually reserved for disabling visual or motor disease.

·        Recently β interferon has been used in clearly relapsingremitting MS to reduce relapse rate by 1/3 and it reduces the number of lesions seen on MRI. However, it is not widely available and its effects are limited.

·        The progressive forms of the disease are more difficult to treat, and immunosuppressive drugs have been used. β interferon may be useful in secondary-progressive MS.

Prognosis

The prognosis of multiple sclerosis is very variable, the relapsing-remitting pattern having a better prognosis than the progressive forms. Death eventually occurs after late-stage disease (optic atrophy, spastic quadriparesis, brain-stem and cerebellar disease) typically from complications of immobility.