Multiple Sclerosis

 

Aetiology

Unknown        15 - 20 times more common in blood relatives than general population.

More common in monozygotic twins           No clear pattern of inheritance

 

Theories

Infection                      Abnormality in myelin lipid constituents      Circulating toxins in the CSF

Autoimmunity High animal fat diet

An autoimmune disorder of the central nervous system resulting from an environmental stimulus in genetically susceptible individuals.

 

Trials

Hyperbaric oxygen                                        Azathioprine (immuno suppressive drug)             

Polyunsaturated Fatty Acids (PUFA)          Various diets eg. (low animal fat)

 

Epidemiology

1 in 800 people in the UK, 50 000 people affected          More common in women than men

More common in temperate climates than tropical regions.

Incidence is related to distance from the equator Onset usually 20 - 40 years

 

Pathology

Multiple areas of demyelination within the brain and spinal cord

Areas of demyelination are disseminated in time and place

Areas of demyelination are initially 2 - 10 mm in size

Phagocytosis of myelin                                Inflammatory changes

Defect is in the oligodendroglial cells        

Only the Central Nervous System is affected - not Schwann cells

Gliosis forms a chronic plaque                    Remyelination seldom occurs

 

Clinical features

Three forms

Relapsing and remitting 90%          Primary progressive 10%    Secondary progressive

Different parts of CNS affected at different times

Many first present with Retrobulbar Neuritis giving blurred vision, areas of visual loss and pain associated with eye movements - recovery is typical after a month

Fatigue                                                                       Spasticity

Diplopia (double vision), vertigo, nystagmus         Limb weakness

Severe, but variable sensory disturbances, resulting in loss of muscle control.

Tingling, stiffness and later problems walking.

Bladder disturbances                                                           Ataxia                        

Slurred speech.                                                                     Undue fatigue.                      

intellectual disturbances                                                       Impotence                 

Nausea                                                                                   Affective alterations                                     

The course of the disease shows great variation between patients.

End result may be tetraplegia

Typical life expectancy is 30 years

 

Diagnosis

MRI is the first line investigation                  Exclusion of other pathology

Delayed visual - evoked responses.           Improvement with ACTH

CSF - inflammatory cells, increased proteins and immunoglobulins, oligoclonal IgG

 

Management 

Drugs

ACTH (Adrenocortiotrophic Hormone), usually for four weeks

Methile Prednisolone, usually one IV injection per day x 3

Other steroids, (do not influence long term outlook)

Beta interferon - reduces the attack rate by one third and reduces number of lesions

Immunosupressants, eg. azothioprine                    Muscle relaxants eg. baclofen

Anti-emetics                                                              Cannabis

 

General measures

Prevent complications of immobility                       Physiotherapy, active and passive exercise.

Occupational therapy                                                Management of intercurrent infections, eg UTI

Honesty

 

DEFINITION

Multiple sclerosis is a chronic inflammatory disease of the central nervous system. Diagnosis requires evidence of lesions that are separated in both time and space and the exclusion of other inflammatory, structural, or hereditary conditions that might give a similar clinical picture. The disease takes three main forms: relapsing and remitting multiple sclerosis, characterised by episodes of neurological dysfunction interspersed with periods of stability; primary progressive multiple sclerosis, where progressive neurological disability occurs from the outset; and secondary progressive multiple sclerosis, where progressive neurological disability occurs later in the course of the disease.

PREVALENCE

Prevalence varies with geography and racial group; it is highest in white populations in temperate regions. [1] In Europe and North America, prevalence is 1/800 people, with an annual incidence of 2–10/100 000, making multiple sclerosis the most common cause of neurological disability in young adults. Age of onset is broad, peaking between 20 and 40 years. [2]

AETIOLOGY

The cause remains unclear, although current evidence suggests that multiple sclerosis is an autoimmune disorder of the central nervous system resulting from an environmental stimulus in genetically susceptible individuals. Multiple sclerosis is currently regarded as a single disorder with clinical variants, but there is some evidence that it may comprise several related disorders with distinct immunological, pathological, and genetic features

PROGNOSIS

In 90% of people, early disease is relapsing and remitting. Although some people follow a relatively benign course over many years, most develop secondary progressive disease, usually 6–10 years after onset. In 10% of people, initial disease is primary progressive. Apart from a minority of people with "aggressive" multiple sclerosis, life expectancy is not greatly affected and the disease course is often of more than 30 years' duration.

AIMS

To prevent or delay disability; to improve function; to alleviate symptoms of spasticity; to prevent complications (contractures, pressure sores); to optimise quality of life

OUTCOMES

Neurological disability, spasticity, fatigue, general health, relapse rate, quality of life. Neurological disability: In clinical trials, disability in multiple sclerosis is usually measured using the disease specific Expanded Disability Status Scale, which ranges from 0 (no disability) to 10 (death from multiple sclerosis) in half point increments. [4] Lower scores (0–4) reflect specific neurological impairments and disability; higher scores reflect reducing levels of mobility (4–7) and upper limb and bulbar function (7–9.5). The scale is non-linear and has been criticised for indicating change poorly, for emphasising neurological examination and mobility, and for failing to reflect other disabilities (e.g. fatigue, sexual disability). Some timed outcomes include ambulation (time taken to walk a specified short distance), the nine-hole peg test (time taken to place some pegs into holes in a block), and the box and block test (time taken to transfer blocks between boxes). Sustained disease progression: This is reported when an increase in disability from either disease progression or incomplete recovery from relapse is sustained for 3 or 6 months. A relapse that resolves within this time period constitutes non-sustained progression. Spasticity: A variety of clinical measures are used, the most common being the Ashworth scale, which scores muscle tone on a scale of 0–4 with 0 representing normal tone and 4 severe spasticity. For the purposes of this review, the Ashworth scale was considered to represent an appropriate clinical outcome and was selected over other outcome measures for spasticity (e.g. neurophysiological measures, examination ratings) that represent proxy clinical outcomes. General health: Attempts have been made to customise generic health status scales, but these scales have not been widely used.