Multiple sclerosis

Published on 19/03/2015 by admin

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Multiple sclerosis

Demyelination is characterized by destruction of normal myelin with relative preservation of axons. By convention, the term demyelination excludes disorders in which there is a failure to form myelin normally (dysmyelination) or a loss of myelin as a result of axonal degeneration. The central nervous system (CNS), peripheral nervous system, or both, may be affected by demyelinating diseases. Disorders characterized by a loss of myelin due to an inherited defect of metabolism are considered in Chapter 22.


This is the commonest demyelinating disease of the CNS. Demyelination is typically multifocal with lesions of different ages. The classic form of the disease usually follows a relapsing and remitting or a progressive course over many years. The cause is not known, but:


Classical (also known as Charcot-type) MS is classified according to its clinical course as:

Two rare, rapidly progressive forms of MS are considered separately: acute (Marburg-type) and concentric sclerosis (Baló’s disease).

Until relatively recently, neuromyelitis optica (Dévic’s disease) was classified as a form of multiple sclerosis but in view of its distinct pathogenesis and pathology, it is now regarded as a separate disease (see Chapter 20).


Geographic and migration studies

image Prevalence varies geographically:

image Migration before 15 years of age from a high- to a low-prevalence area reduces the likelihood of developing MS.

image Migration before 15 years of age from a low- to a high-prevalence area increases a person’s risk of developing MS, even above that of the natives.

image Temporal and spatial clustering of cases in the Faroe Islands in 1943 and subsequently (‘epidemics’ of MS) suggest introduction of an infective agent by occupying British troops during the World War II. Outbreaks of MS have also occurred in Iceland and the Orkneys.

image Low vitamin D level has been implicated as one possible risk factor.

Family, twin, racial, and genetic studies

image The risk of developing MS is increased 15–20-fold in first-degree relatives of patients with this disorder.

image The concordance rate of MS is significantly higher in monozygotic twins than in dizygotic twins.

image The incidence is low in some racial groups, including African blacks, Japanese and Chinese (and probably other oriental populations), and Asians from (and probably those living in) India and Pakistan.

image Some studies suggest that apolipoprotein E ε4 carriers with MS are more likely to have severe disease, and ε2 carriers mild disease.

image The risk of MS is probably influenced by independent or epistatic effects of several genes each with small individual effects, rather than a very few genes of major biological importance.

image Genome-wide association studies have shown significant association of MS with multiple genes, most related to immune function (e.g. HLA-DRB1, IL2RA, IL7R, TAGAP, CLEC16A, CD226, CD5, IL12B, IL22RA2, TNFRSF1A, TNFRSF14, CD86, CD58, CD40, CLEC1) or signal transduction (e.g. CBLB, GPR65, MALT1, RGS1, STAT3, TAGAP, TYK2). Two genes involved in vitamin D metabolism (CYP27B1, CYP24A1) have also been associated with MS.



In fixed tissue the patches of demyelination appear as well-demarcated regions of gray discoloration (plaques), that:

image Vary in size, shape, number, and distribution (Fig. 19.1).

image May extend to the surface of the brain stem and spinal cord, forming gray depressions on external examination (Fig. 19.1).

image May be seen in the olfactory tracts and are frequently present in the optic nerves (Fig. 19.2).

image Are often present adjacent to the lateral angles of the lateral ventricles on sectioning the cerebrum (Fig. 19.3).

image Can occur anywhere in the white matter, at the junction between the cerebral gray and white matter (Fig. 19.4), and within the cortical gray matter and deep gray nuclei (Fig. 19.5), which include myelinated axons as well as neuronal somata and dendrites.

image May occur in the cerebellar white matter and peduncles, in the floor of the fourth ventricle, elsewhere in the brain stem (Fig. 19.6, see also Fig. 19.1c), and in the spinal cord (Fig. 19.6, see also Fig. 19.2a).


image Commonly presents with weakness, paresthesia, and sensory loss involving one or more limbs, optic neuritis, diplopia, incoordination, and vertigo.

image Can also cause loss of vision, dysarthria, disturbances of micturition, constipation, painful muscle spasms, trigeminal neuralgia, cognitive impairment, seizures, and Lhermitte’s sign.

image Usually associated with demonstrable foci of demyelination on MRI (gray matter plaques are more difficult to detect than those in the white matter and are best imaged using fast fluid-attenuated inversion recovery or double inversion recovery sequences).

image Particularly in progressive forms of disease, tends to cause atrophy that can affect gray or white matter and often involves the spinal cord.

image Often associated with delayed visual evoked responses.

image Usually associated with oligoclonal bands of immunoglobulins on electrophoresis of the cerebrospinal fluid.

image Can produce clinical features and CT scan and MRI appearances that mimic those of a brain neoplasm and lead to biopsy.

image Often initially pursues a relapsing and remitting course, but can be progressive from the outset and tends eventually to become progressive after initial remissions (see Classification, above). The interval between relapses is variable, and the latent phase between the onset of disease and the first relapse can be many years.

Several sets of diagnostic criteria have been proposed. Current guidelines are shown in Table 19.1.

Brain stem and spinal plaques are usually more difficult to see by macroscopic inspection than are those in the cerebral white matter. However, there may be obvious atrophy of the affected regions of spinal cord. The optic nerves and chiasm may also appear gray and atrophic, often asymmetrically.

Plaques containing many lipid-laden macrophages tend to appear slightly yellow or chalky white rather than gray (Fig. 19.7

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