Multiple sclerosis

Published on 03/03/2015 by admin

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Last modified 22/04/2025

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Multiple sclerosis

Definitions

Multiple sclerosis (MS) is defined as a chronic, inflammatory, demyelinating auto-immunological disease. The name multiple sclerosis refers to the scars (sclerosis), known as plaques, formed in the nervous system. There are four types of MS classified according to the course/progression of the disease process.

Benign MS

This subgroup is diagnosed retrospectively. These individuals show little or no disease progression.

Relapsing remitting MS

This is the most common type of MS representing 80% of the people diagnosed with MS. Symptoms occur for a period of time (relapse, exacerbation) and then improve (remission), either partially or completely.

Secondary progressive MS

This type is a progression of relapsing remitting MS, when the individual shows a sustained deterioration for at least 6 months. On average, by 15 years, around two-thirds of people with relapsing remitting MS will have developed secondary progressive MS.

Primary progressive MS

This form of MS affects around 10% of the people diagnosed. The course of the disease begins with subtle problems that worsen over time. There is no relapse remitting pattern, their MS is progressive from the beginning.

Epidemiology

Prevalence

According to government guidelines, MS is diagnosed in 3.5–6.6 people per 100 000 of the population each year in England and Wales.

Age

MS is usually diagnosed between the ages of 20 and 50 years.

Gender

Approximately, the ratio of women to men affected is 2:1.

Geography

MS occurs with much greater frequency in areas that are farther away from the equator.

Aetiology

The definitive cause is unknown. However, the evidence suggests that the cause may be a combination of both genetic and environmental factors.

Environmental factors

Viral infection

The evidence indicates that a viral infection, produced by a widespread microbe rather than a rare pathogen, could be the origin of the disease. For example, human herpes virus, chicken pox and glandular fever.

Vitamin D deficiency

Vitamin D deficiency has been linked with a higher risk of MS. This may occur as a result of inadequate intake of the vitamin, coupled with a lack of exposure to sunlight and may explain the geographical distribution of MS in countries further away from the equator.

Other factors: environmental

Severe stress, smoking and occupational exposure to toxins may be risk factors, although the supporting evidence is weak.

Genetic factors

MS is not considered a hereditary disease. However, genetics may play a role in determining a person’s susceptibility to MS.

Familial

The risk of acquiring MS is higher in relatives of a person with the disease than in the general population.

Specific genes

Differences in the human leukocyte antigen (HLA) system increase the probability of MS. These are a group of genes residing on chromosome 6 vital in immune system function. Two other genes have been shown to be linked to MS. These are the IL2RA and the IL7RA. Mutations in these receptor genes are already known to be associated with other autoimmune conditions.

Pathology

Although the initial trigger is unknown, the damage to the nervous system in MS is believed to be caused by the patient’s own immune system. Lesions most commonly involve the white matter of the central nervous system in a process of demyelination. The peripheral nervous system is rarely involved.

The process of demyelination

The process of demyelination appears complex with the end result being damage or destruction of the oligodendrocytes in the central nervous system by lymphocytes (white blood cells) in the immune system. This results in an inflammatory response which stimulates other immune cells, causing a number of other damaging effects such as swelling, activation of macrophages and other destructive proteins and a change in the blood–brain barrier integrity. Unlike the peripheral nervous system, damage to central nervous system is not followed by extensive regeneration as it is limited by hostile glial cells and the extracellular environment. Nevertheless, some remyelination has been found to take place in the early phases of the disease. Repeated attacks however, lead to successively fewer effective remyelinations, until a scar-like plaque (sclerosis) is built up around the damaged axons.

Axonal loss

Although inflammation and demyelination has long been implicated in the pathology of MS, recent research has shown that there is also widespread loss of nerve axons in the central nervous system. The relationship between inflammation and this axonal loss is not yet fully understood, however the loss of axons is thought to be the main factor in MS progression.

Outcome and prognosis

The process of demyelination results in a thinning or complete loss of myelin (Fig. 2.1) and as the disease advances, the destruction of the nerve axons. The nervous system depends crucially on the myelin sheath for insulation and support and for fast nerve conduction (S2.6) so that when the myelin is lost, the neuron no longer conducts electrical signals effectively. Of course with axon destruction, it is impossible for the neuron to conduct signals. The outcome of these processes means that communication between different parts of the central nervous system is slow, inaccurate or non-functional.

Figure 2.1 (A) Normal myelin sheath. (B) Demyelination in multiple sclerosis.

The life expectancy of an individual with MS is more or less normal. However, the mortality for older patients and those with longer disease duration is slightly higher in MS patients.

Signs and symptoms

MS is an extremely variable condition. Signs and symptoms develop as the cumulative result of multiple lesions in the central nervous system. Sites of demyelination include the cerebral cortex, brain stem, spinal cord, basal ganglia, cerebellum and the cranial nerves. Understanding the function of these different areas of the brain (S2.7, 9, 10, 11, 12, 13, 14, 15) will give the therapist a platform by which to reason the potential clinical presentation.

The signs and symptoms presented will be a complex array of:

• Cognitive and perceptual

• Secondary complications

Physical

Speech (S3.16)

• Dysphasia: expressive/receptive

• Dysarthria (cranial nerves VII, IX and XII)

Swallow (S3.16)

• Dysphagia (cranial nerves IX and XII)

Sensorimotor

• Altered muscle tone (S3.21)

• Altered sensation (S3.23)

• Altered reflexes (S3.22)

• Poor coordination (S3.26)

• Pain (S3.29)

• Visual deficits (S3.27)

• Poor balance (S3.32).

Cognitive and perceptual (S3.16, 17, 18, 33)

• Inattention, neglect

• Problems with colour, depth, figure ground, form constancy, size constancy

• Problems spatial relations for example up/down, in/out, left/right, 2D/3D

• Altered body scheme, e.g. altered midline orientation, pusher syndrome

• Agnosia: problems with recall/recognition

• Poor memory: short-term or long-term memory

• Problems with higher executive functions, e.g. planning, organization, problem solving, self-initiation, monitoring and inhibition.

Secondary complications

• Psychosocial (S3.16): Depression, anxiety, lack of confidence, change of role, financial

• Change in postural alignment (S3.20)

• Poor core stability (S3.25)

• Altered gait (S3.19)

• Decreased muscle strength (S3.30)

• Decreased range of movement (S3.28)

• Reduced function (S3.18)

• Falls (S3.34).

References and Further Reading

Alonso, A, Jick, SS, Olek, MJ, et al. Incidence of multiple sclerosis in the United Kingdom: findings from a population-based cohort. Journal of Neurology. 2007; 254:1736–1741.

Ascherio, A, Munger, KL. Environmental risk factors for multiple sclerosis. Part I: the role of infection. Annals of Neurology. 2007; 61:288–299.

Ascherio, A, Munger, KL. Environmental risk factors for multiple sclerosis. Part II: noninfectious factors. Annals of Neurology. 2007; 61:504–513.

Aulchenko, YS, Hoppenbrouwers, IA, Ramagopalan, SV, et al. Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis. Nature Genetics. 2008; 40:1402–1403.

Chari, DM. Remyelination in multiple sclerosis. International Review of Neurobiology. 2007; 79:589–620.

Christensen, T. Human herpes viruses in MS. International MS Journal. 2007; 14:41–47.

Compston, A, Coles, A. Multiple sclerosis. Lancet. 2002; 359:1221–1231.

Filippi, M, Bozzali, M, Rovaris, M, et al. Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain. 2003; 126:433–437.

Islam, T, Gauderman, J, Cozen, W, et al. Differential twin concordance for multiple sclerosis by latitude of birthplace. Annals of Neurology. 2006; 60:56–64.

Lünemann, JD, Kamradt, T, Martin, R, et al. Epstein Barr virus: environmental trigger of multiple sclerosis. Journal of Virology. 2007; 81:6777–6784.

Marrie, RA. Environmental risk factors in multiple sclerosis aetiology. Lancet: Neurology. 2004; 3:709–718.

MS Society www.mssociety.org

Munger, KL, Levin, LI, Hollis, BW, et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. Journal of the American Medical Association. 2006; 296:2832–2838.

Pascual, AM, Martínez-Bisbal, MC, Boscá, I, et al. Axonal loss is progressive and partly dissociated from lesion load in early multiple sclerosis. Neurology. 2007; 69:63–67.

Ragonese, P, Aridon, P, Salemi, G. Mortality in multiple sclerosis: a review. European Journal of Neurology. 2008; 15:123–127.

Ramsaransing, GS, De Keyser, J. Benign course in multiple sclerosis: a review. Acta Orthopaedica Scandinavica. 2006; 113:359–369.

Royal College of Physicians. Multiple sclerosis: national clinical guideline for diagnosis and management in primary and secondary care. www.rcplondon.ac.uk, 2004.

Svejgaard, A. The immunogenetics of multiple sclerosis. Immunogenetics. 2008; 60:275–286.

Waubant, E. Biomarkers indicative of blood-brain barrier disruption in multiple sclerosis. Disease Markers. 2006; 22:235–244.

Weber, F, Fontaine, B, Cournu-Rebeix, I, et al. IL2RA and IL7RA genes confer susceptibility for multiple sclerosis in two independent European populations. Genes and Immunity. 2008; 9:259–263.

World Health Organization. Neurological disorders: a public health challenge. www.who.int/mental_health/neurology/neurological_disorders_report_web.pdf, 2006.

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