MS is a common disease of unknown cause in which there are multiple areas of demyelination within the brain and spinal cord. These are ‘disseminated in time and place’ (hence the old name ‘disseminated sclerosis’). An acquired defect in the oligodendroglial cells that produce myelin is responsible. The commonest age of onset is between 20 and 35 years, the disease being commoner in women. In the UK MS causes disability of varying degree in over 50000 people.
PREVALENCE
The disease occurs worldwide, but the prevalence varies widely, being directly proportional to the distance from the equator. At 50-650 N (roughly Land’s End to Iceland) the prevalence is 60-100 per 100000 people; at latitudes less than 300 N the prevalence is less than 10 per 100 000; and at the equator it is a rarity. In the Southern Hemisphere the variation is similar, with progressive increase in prevalence away from the equator.
AETIOLOGY
The cause of the disease is unknown. Familial incidenceand HLA linkage First-degree relatives of a patient have an increased chance of developing MS, although there is no clear-cut pattern of inheritance. There is an increased concordance amongst monozygotic twins. In Caucasians in northern Europe and the USA, there is a positive association between MS and antigens HLAA3, B7 and DRl. Infection Although efforts to transmit MS experimentally have been uniformly unsuccessful, there is an abnormal immune response in MS patients, with an increase in the titres of serum and CSF antibodies to many common viruses, particularly measles.
Certain epidemic transmissible zoonoses, such as scrapie, a demyelinating disease in sheep, are pathologically similar to MS. Human T-cell leukaemia virus 1 (HTLV- 1) infection in humans (tropical spastic paraparesis) is an example of a viral demyelinating disease. Diet
It has been suggested that MS is related to the consumption of large quantities of animal fats. Surveys in Norway have shown that MS is distinctly uncommon in coastal fishing communities compared with agricultural areas. However, the role of diet is particularly difficult to
evaluate.
PATHOLOGY
The essential features are plaques of demyelination, initially 2-10 mm in size (Fig. 18.19). These lesions ire perivenular and have a predilection for the following sites within the brain and spinal cord:
• Optic nerves
• Brain stem and its cerebellar connections
• Cervical cord
• Periventricular region
Plaques rarely destroy large groups of neighbouring anterior horn cells (so that muscle wasting is unusual) and never occur in the myelin sheaths of peripheral nerves. Remyelination seldom occurs and the mechanism of the remission of symptoms is unclear.
CLINICAL FEATURES
No single group of signs or symptoms is diagnostic ofMS. Despite this, the disease is often recognizable on PREVALENCE The disease occurs worldwide, but the prevalence varies widely, being directly proportional to the distance from the equator. At 50-650 N (roughly Land’s End to Iceland) the prevalence is 60-100 per 100000 people; at latitudesless than 300 N the prevalence is less than 10 per 100 000; and at the equator it is a rarity. In the Southern Hemisphere the variation is similar, with progressive increase in prevalence away from the equator.
AETIOLOGY
The cause of the disease is unknown. Familial incidence and HLA linkage First-degree relatives of a patient have an increased chance f developing MS, although there is no clear-cut pattern of inheritance. There is an increased concordance amongst monozygotic twins.In Caucasians in northern Europe and the USA, there is a positive association between MS and antigens HLAA3, B7 and DRl.
Infection
Although efforts to transmit MS experimentally have been uniformly unsuccessful, there is an abnormal immune response in MS patients, with an increase in the titres of serum and CSF antibodies to many common viruses, particularly measles.
Certain epidemic transmissible zoonoses, such as scrapie, a demyelinating disease in sheep, are pathologically similar to MS. Human T-cell leukaemia virus 1 (HTLV- 1) infection in humans (tropical spastic paraparesis) is an example of a viral demyelinating disease.
Diet It has been suggested that MS is related to the consumption of large quantities of animal fats. Surveys in Norway have shown that MS is distinctly uncommon in coastal fishing communities compared with agricultural areas. However, the role of diet is particularly difficult to
evaluate.
PATHOLOGY
The essential features are plaques of demyelination, initially 2-10 mm in size (Fig. 18.19). These lesions ire perivenular and have a predilection for the following sites
within the brain and spinal cord:
• Optic nerves
• Brain stem and its cerebellar connections
• Cervical cord
• Periventricular region
Plaques rarely destroy large groups of neighbouring anterior horn cells (so that muscle wasting is unusual) and never occur in the myelin sheaths of peripheral nerves. Remyelination seldom occurs and the mechanism of the remission of symptoms is unclear.
CLINICAL FEATURES
No single group of signs or symptoms is diagnostic of MS. Despite this, the disease is often recognizable on clinical grounds. There are two patterns:
1 Relapsing and remitting MS with lesions occurring in different parts of the CNS at different times
2 Chronic progressive MS (approximately 20%) Common presentations of MS are described below.
ptic neuropathy (ON)
SYMPTOMS. The patient complains of blurring of vision in one eye. Mild ocular pain is usual. The symptoms progress, usually over days, to produce severe visual loss. Recovery occurs, typically within a month. Bilateral ON occasionally occurs. SIGNS. The signs of ON depend upon the site of the plaque. When the lesion is in the optic nerve head there is disc swelling (optic neuritis). If the lesion is several millimetres proximal to the disc there are often no ophthalmoscopic features (‘the doctor sees nothing and the patient sees nothing’); this is known as retrobulbar neuritis.
Optic neuritis is easily distinguished from papilloedema of other causes by the presence of early visual loss. A relative afferent pupillary defect is often present in the early stages. This persists after recovery.
SEQUELAE. There are usually no residual symptoms, but small scotomata and defects in colour vision can be demonstrated. Following the attack, disc pallor appears (optic atrophy), first in the temporal region and then spreading to affect the whole disc. The visual evoked responses (VER) remain abnormal (see below).
Brain stem demyelination
An acute episode affecting the brain stem causes diplopia, vertigo, facial numbness or dysphagia. ‘Pyramidal’ signs in the limbs occur when the corticospinal tracts are involved.
A typical picture is sudden diplopia and vertigo with nystagmus, but without tinnitus or deafness. This lasts for some weeks before recovery. Diplopia in MS may be caused by many different lesions-a sixth nerve lesion and an internuclear ophthalmoplegia (INO) are two examples.
Cord lesion
A spastic paraparesis is caused by demyelination in the cord. There is difficulty in walking and sensory disturbance. Urinary symptoms are common. In the initial episode it may be impossible to decide, even with specialized tests, whether or not a lesion is due to demyelination. The appearance of subsequent lesions confirms the diagnosis. Remissions may last for many years; their length is unpredictable.
Unusual presentations
Epilepsy occurs more commonly in MS patients than in he general population. So, too, does trigeminal neuralgia (see p. 887). Tonic spasms or brief spasms of a limb are other unusual symptoms of this disease.
End-stage multiple sclerosis In the later stages of the disease the patient is severely disabled with a combination of spastic tetraparesis, ataxia,
optic atrophy, nystagmus, brain stem signs, pseudobulbar palsy and incontinence of urine. Dementia is common. Death follows from uraemia and/or bronchopneumonia.
DIFFERENTIAL DIAGNOSIS
Few other neurological diseases of young people follow asimilar relapsing and remitting course. Thromboembolism causes symptoms that are characteristically more sudden in onset. Other degenerative conditions, such as Friedreich’s ataxia, are gradually progressive, without remissions.
Initially individual plaques (e.g. in the optic nerve, brain stem or cord) may cause diagnostic difficulty; they must be distinguished from compressive, inflammatory, mass or vascular lesions.
CNS sarcoidosis, SLE and Behcet’s syndrome may mimic the relapsing pattern of MS.
INVESTIGATION
MRI of the brain is now the first-line investigation. Multipleplaques are visible, principally in the periventricular region and brain stem (see Fig. 18.2). The lesions are rarely visible on CT scan. Examination of the peripheral blood and urine is unhelpful and there are no features on plain X-rays. Table 18.40 summarizes the changes seen in the CSF. The appearance and pressure of the fluid and the level of glucose are normal, and serological tests for syphilis are negative. The presence of oligoclonal bands of IgG indicate the production of immunoglobulin (to unknown antigens) within the CNS. This investigation is now being superseded by MR!.
Electrophysiological tests
Delay in the visual-evoked response (VER) follows opticneuropathy. As some attacks are subclinical, a delayed VER may provide evidence of a second lesion within the CNS in, for example, an undiagnosed cord lesion. Brain stem and somatosensory evoked potentials are also sometimes measured. Peripheral nerve studies are normal. EEG recordings are unhelpful.
MANAGEMENT AND PROGNOSIS Once diagnosed, practical decisions need to be taken about employment, home and plans for the future in the face of a potentially disabling disease for which there is no curative treatment. It is now usual practice to informpatients of the diagnosis. There is no method of predicting the course of MS but there is wide variation in its severity. Many MS patients live self-sufficient, productive lives while others are ravely disabled.
Wise counsel and honesty, tempeed with reassurance of the benign course of many cases of MS, is important. Many forms of therapy have been suggested for MS, including cryotherapy, pyrotherapy, vaccines, purified protein derivative (PPD), transfer factor, electrical stimulation, gluten-free diets, sunflower seed oil, arsenicals and hyperbaric oxygen. None of these has been shown to benfit patients.
Short courses of ACTH and corticosteroids are usedwidely in exacerbations and do sometimes appear to reduce temporarily the effect of a relapse. They do not influence the outlook in the long term. Immunosuppressants (azathioprine, cyclophosphamide) are also used, but there is no agreement about their value. Recently f3 interferonhas been shown to reduce the attack rate by a third and reduces the number of lesions seen on MRI. In any chronic neurological disease, treatment of intercurrent infections is important. Urinary infection frequently exacerbates the symptoms.
Muscle relaxants (e.g. baclofen, benzodiazepines and antrolene) reduce the pain and discomfort of spasticity, articularly when there are flexor spasms of the lower limbs. Prevention of bed sores is vital.
Other measures
There is much that should be done for a patient with any chronic neurological disease. Practical advice at work, on walking aids, wheelchairs, car conversions, alterations to houses and gardens can be given. Support in a wide range of areas from fear and reactive depression to the sexual difficulties of the disabled is also helpful. Liaison between family practitioner, physiotherapist, occupational therapist and social worker is important.
