Incidence -

Multiple sclerosis affects around 50, 000 people in the UK
Lifetime UK risk is 1 in 1000

Age -

Mean age of onset is 30 years


Female preponderance

Geography -

More common in temperate climates, but prevalence is variable
Prevalence in England is around 40/100,000 whereas in Orkney and Shetland it is around 120/100,000
Much less common in Black Africa and Asia

Aetiology -

Presumed to be a disorder of altered immune response
Altered immune response which targets the central nervous system.
Some degree of genetic susceptibility followed by as yet undefined environmental triggers (e.g. viral triggers)
Although infection has not been shown to directly cause MS, increased titres of serum and CSF antibodies to many common viruses, particularly measles are found in MS patients.
Diet has also been related to MS, particularly consumption of large quantities of animal fats.

Pathology -

MS is an inflammatory disease which causes relapsing episodes of demyelination of the brain and spinal cord. MS may be classified as relapsing remitting type, primary progressive, secondary progressive or secondary to other disease.
Demyelinated areas are called plaques and may occur anywhere in the CNS, but are most commonly seen in the cerebellar penduncles, brain stem and at the angles of the lateral ventricles.
Relapsing remitting is characterised by episodes of monophasic neurological disturbance with return to normal function between attacks.
Secondary progressive MS is when the patient doesn’t return to their normal function between attacks resulting in progressive dysfunction with superimposed relapses.
Primary progressive MS is when there is progressive disease from the outset. This form is more common in males and generally presents later.
MS may occur as a secondary process to a number of diseases such as leucodystrophies, Binswanger’s disease (caused by ischaemic damage to myelin due to widespread cerebral arteriosclerosis) and progressive multifocal leucoencephalopathy (caused by infection with the parvovirus, seen in immunocompromised pts).

Macroscopic Changes -

Areas of demyelination appear differently macroscopically depending upon whether there is recent active or old demyelination.
Macroscopically areas of recent active demyelination appear salmon-pink granular patches of softening in white matter.
Old myelin loss appears as patches of firm, gelatinous, grey-pink coloured tissue which is well demarcated from surrounding normal CNS.

Microscopic Changes -

Microscopically there is myelin loss and inflammatory cells are present in active demyelination
Details of microscopic changes seen
Areas of recent active demyelination show myelin loss associated with the presence of inflammatory cells such as lymphocytes and macrophages.
Macrophages phagocytose the damaged myelin and become foam cells.
The plaque margins may show enlarged astrocytes in active lesions
In old plaques there is demyelination without inflammatory cells, and they are occupied by astrocytes.
Most of the axons spanning a plaque are preserved but a small proportion are lost.


MS doesn’t spread, but may affect all areas of the CNS.


MS affects the central nervous system (brain, spinal cord and central nervous system parts of the cranial nerves).

Clinical Features -

MS commonly causes symptoms in the eyes, upper motor neurone symptoms in arms and legs (spastic tetraparesis; just in legs – spastic paraparesis), and patchy sensory disturbance. May cause problems in bladder, bowel, swallowing and sexual function.
EYES: eye signs in MS are optic neuritis and subsequent optic atrophy, and internuclear ophthalmoplegia.
Optic neuritis presents acutely with pain on eye movement and blurred vision. Visual disturbance is generally a central visual defect or scotomas.
Examination may reveal a relative afferent pupillary defect (RAPD) and chronically fundoscopy may show optic atrophy as evidenced by a pale optic disc.
RAPD: shown by the swinging light test. When the light is shone in the affected eye the pupil constricts and the other pupil constricts via the consensual reflex. When the light is then shone in the good eye that pupil constricts and the pupil of the bad eye constrict by the consensual reflex. The light is then shone in the bad eye again and the pupil appears to dilate. This is because the consensual reflex from the good eye is stronger than the direct light reflex in the bad eye and so it appears to dilate.
Internuclear ophthalmoplegia: found on eye movements. The abducting eye shows nystagmus and the adducting eye shows incomplete movement in the direction it is supposed to be looking (non-conjugate gaze). This is due to lesions of the internuclear tracts that link the nuclei of the nerves controlling the extraocular muscles.
MOTOR: weakness due to pyramidal tract damage. Arms are weaker in extension and legs are weaker in flexion. Spasticity (increased tone) due to upper motor neurone lesions .Hyper-reflexia, clonus and up-going plantars.
Pain: trigeminal neuralgia-like syndrome, dyaesthesia
Recurrent facial palsy
Cerebellar signs: ataxia, intention tremor
Loss of proprioception, temperature and pain sensation
Depression, cognitive and memory problems, fatigue, dementia
Bowel and bladder dysfunction
Sexual dysfunction
Swallowing disorders
Deafness and vertigo
Rarely aphasia and epilepsy.

Investigations -

Diagnosis of MS involves clinical assessment, CSF examination, evoked potentials, and MRI.
No test is pathognomonic.
CSF: normal of <50 lymphocytes/mm3, increased protein <1g/L +/- oligoclonal bands of IgG on electrophoresis
Delayed visual, auditory and somatosensory evoked potentials
MRI is sensitive but non-specific for plaque detection and helps show other causes, e.g. cord compression.

Management -

There is no cure for MS, patient education and advice is vital as is a MDT approach to difficulties encountered due to the disease. Acute relapses may be treated with steroids. Beta-interferon has been used to try and reduce the number of relapses.
Methylprednisolone: 1g/24h IV for 3 days shortens relapses.
Beta-interferon: may decrease relapse rate by 1/3. V expensive. Side effects include flu like symptoms, depression and abortion. Contraindications are depression, active liver disease, pregnancy/lactation and uncontrolled epilepsy.
Palliation may include the use of baclofen for spasticity (15-100mg/day PO) and diazepam (2-15mg/24h PO).
Need to address difficulties with bowel, bladder and sexual dysfunction appropriately as well as financial, social and occupational impacts of disease.


MS can have a wide variety of clinical features as described above, but does not lead to specific complications.

Prognosis -

MS in most patients does not shorted life. There is generally an increasing burden of disability over decades.
At 5 years 70% of patients are still employed.
Poor prognostic factors are: male sex, older age at onset, motor signs at onset, short interval between 1st and 2nd attack, early disability, many lesions on MRI and many relapses in the early years.
Primary progressive MS has a poor prognosis.