All the facts you need to know about multiple sclerosis

Multiple sclerosis (MS) is a chronic demyelinating disease that follows a fluctuating and unpredictable course. It is a major cause of disability in young adults.

Epidemiology

There is marked geographical variation in MS, characterized by increasing frequency with increasing latitude north or south from the Equator. Scotland has the highest incidence of MS in the world (12 per 100 000) compared to 6 per 100 000 in England.

The age of onset is usually between 20 and 40 years though primary progressive MS tends to occur after the age of 40. The risk of developing MS is also increased if a first-degree relative (sibling or parent) is affected.

Pathology

The basic pathological change in MS is patchy degeneration of the myelin sheath resulting in 'plaques' of demyelination. As a consequence, nerve impulse transmission is delayed.

The exact aetiology of MS is unknown. It is thought to be an autoimmune disorder mediated by T cells associated with specific HLA antigen. Environmental factors also playa role: moving at a young age from an area of low risk to high risk can also increase the risk. A possible viral agent is therefore thought to play a role but no single agent has been conclusively identified.

Scope of disease

The frequency of complications that can result from MS increases with severity and duration of the disease

Clinical features

The clinical features of MS depend on the site of demyelination. Symptoms are often exacerbated by heat or exercise (Uhthoff's phenomenon).

Unilateral visual loss can occur due to demyelination of the optic nerve, the most common cause of optic neuritis. There is gradual loss of vision with red colour desaturation. Eye movements may be painful and examination of the eye can reveal an afferent pupillary defect with normal fundus. Eventually optic atrophy develops.

Motor involvement may cause a spastic paraparesis or unilateral weakness. Spasticity may be a marked problem. The clinical signs are of an upper motor neurone lesion, that is increased tone, clonus, hyperreflexia and extensor plantar responses.

Sensory disturbance is common with sensory loss or, more often, non-specific paraesthesia. Neck flexion may cause lightning pains shooting down the body (Lhermitte's phenomenon).

Brainstem and cerebellar involvement can give rise to vertigo, vomiting, dysarthria, incoordination and ataxia. Eye movements may be abnormal with internuclear ophthalmoplegia or nystagmus.

Urinary symptoms are common, particularly frequency and urgency.

The diagnosis of MS depends on lesions being disseminated in time and space. After one clinical attack the diagnosis of MS cannot be made (this is referred to as a clinically isolated syndrome) unless an MRI scan also indicates lesions disseminated in time and space.

Disease subtypes

There are four types of MS. The majority of patients will start with the relapsing remitting type (80-90%). An attack (relapse) is followed by a remission during which disability does not progress. A relapse lasts for a minimum of 24 hours but usually lasts several weeks. Recovery from a relapse can be complete or partial and a second attack can cause the same or new symptoms.

Secondary progressive MS is characterized by slow deterioration with increasing disability (in addition there may still be relapses). Primary progressive MS is a form of MS with no history of relapses or remissions and a slow and insidious course; it occurs in approximately 10%. Benign MS does not tend to get worse over time or result in permanent disability.

Initial investigations

MRI of the brain and spinal cord

MRI of the brain (and spinal cord if there are symptoms suggestive of spinal involvement) is an excellent tool for evaluating a patient with suspected MS, as 95% with clinically definite MS will have an abnormal brain MRI scan. New lesions can be identified by the use of gadolinium contrast. MRI can also assist in the evaluation of the prognosis of the disease. After the first attack of demyelination, an abnormal MRI scan suggests a high risk of developing MS (83% risk at 10 years), but with a normal scan the risk is 11% at 10 years.

Visual evoked potentials (VEPs)

A delay in the visual evoked potentials is indicative of demyelination, particularly if this is asymmetrical. VEPs can be abnormal even if there is no history of clinical involvement.

Lumbar puncture

Oligoclonal bands (unmatched in the serum) may be present in the cerebrospinal fluid. This is indicative of inflammation within the central nervous system and is not specific to demyelination although oligoclonal bands are present in 95% of clinically definite cases of MS. The lymphocyte count and protein level can be slightly raised.

Initial management

Multidisciplinary team management

Patient education, counselling and the support of a multidisciplinary team is crucial for patients with MS. Physiotherapy, occupational therapy and specialist MS nurses can all help with emotional and physical support.

Medical therapy

There is no cure for MS and treatment is aimed at relieving symptoms, preventing relapses and delaying disease progression.

Corticosteroids

A short course of high-dose methylprednisolone (oral or intravenous) is given to shorten the relapse time but corticosteroids have no effect on disease progression.

Disease-modifying agents

Interferon-beta

The most commonly given disease-modifying agent is interferon-beta, which both reduces relapse rate and delays disease progression. The indications for treatment are relapsing remitting MS if the patient is able to walk independently (at least 100 metres without assistance) and has had at least 2 clinically significant relapses in the last 2 years. It is not currently recommended in the treatment of clinically isolated MS or secondary progressive MS unless the patient has had at least 2 clinically significant relapses in the last 2 years, is able to walk 10 metres without assistance, and the disability from slow disease progression is minimal.

Other disease-modifying agents

Other treatments include glatiramer acetate, azathioprine, mitoxantrone and plasma exchange.

Prognosis

The overall life expectancy of patients with MS is shortened by 5-7 years; however, the disease process is very variable and ranges from no disability and few relapses to frequent relapses, rapid progression of disability and early death.

The main indicator of a poor prognosis is the onset of the progressive phase of disease. Other indicators include frequent relapses in the first 2 years, short intervals between attacks and female sex.


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