Multiple Sclerosis

Muhammad Usman
Introduction
● Multiple sclerosis (MS) is a chronic disease affecting the central nervous system (the brain
and spinal cord). MS occurs when the immune system attacks nerve fibers and myelin
sheathing (a fatty substance which surrounds/insulates healthy nerve fibers) in the brain
and spinal cord. Multiple sclerosis is the most common central nervous system disorder to
affect young and middle-aged adults.Because the disease process has such protean
manifestations and a variable course, demyelinating disorders have a broad clinical
spectrum, ranging from a single benign episode to one that is potentially fatal.
Epidemiologic studies demonstrate that MS is more prevalent in northern latitudes, twice
as common in women, and most often presents during the third and fourth decades.
Caucasians are twice as likely as people of color to acquire MS in the United States and
Canada. Interestingly,when MS develops among Asian populations, it predominantly
affects the optic nerves and spinal cord with much less involvement of the brain in
contrast to North American and European persons.Individuals born in a northern latitude,
who are race and age-matched, gain the innate diminished risk of equatorial region
habitats if they move south before age 15 years.
● Other persons who also move from the north to the south, but do not do so until after age
15 years, maintain their innate higher risks.Although there are some yet to be precisely
identified genetic predisposing factors for MS, these alone cannot account for the above-
defined variabilities, as genetically comparable populations vary in MS prevalence
depending on place of birth and age of migration.
Genetic Factors
● There is no well-defined typical genetic pattern defined on review of the natural
heritability of MS. However occasional familial disease clusters do exist. The risk of MS
in a first-degree relative of an affected individual (estimated at 1 in 500–1000) is
approximately 20 times that in the general population. Of patients with MS, 10–15% have
at least one affected firstdegree relative, but the risk is not much different for parent–child
relationships than for other relationships, thus negating typical dominant, recessive, or sex-
linked inheritance. The risk of MS in first-degree relatives is never greater than 5%,except
in monozygotic twins, where concordance rates are approximately 25%.
● It is unlikely that any single gene is responsible for conferring susceptibility; therefore, a
polygenic mode of transmission is assumed. Comparison of concordance rates between
half siblings reared together and those reared apart demonstrates no significant difference,
suggesting that environment does not account for the slightly higher rate of MS in half-
siblings of affected persons. Furthermore, it does not matter whether the shared biologic
parent is the mother or the father. Thus, a mitochondrial inheritance pattern is most
unlikely.
Pathology
● With classic MS, the primary process is one of demyelination leading to loss of myelin
from central nervous system (CNS) axons. Myelin loss (a nonspecific term) occurs
concurrently with other pathologic processes that also affect the axons, glial elements, or
vasculature. CNS oligodendrocytes are responsible for the elaboration of brain myelin.
This is a predominantly lipid-based (70%) structure, with the remainder being protein
based. One part, myelin basic protein, is particularly immunologically susceptible and
experimentally encephalitogenic.
● Inspection of the gross brain of an MS subject does not demonstrate any sign of
abnormalities that would indicate the presence of the myriad histologic changes that are to
be found on microscopic evaluation. However, the optic nerves, optic chiasm, and spinal
cord may be atrophic to the native eye. Sometimes, areas of patchy demyelination are seen
on the basis pontis surface, the cerebellar peduncles, and the surface of the medulla and
floor of the fourth ventricle.Coronal brain sections reveal changes similar to those noted
on MRI, where variously sized MS plaques are apparent.Recently acquired lesions are
pink and soft, whereas chronic MS lesions are gray, translucent, and firm.It is often
difficult to correlate the multiple lesions found at autopsy or by MRI throughout the
neuraxis with a patient’s history.
● Sometimes classic MS plaques exist in patients who were never clinically suspected of
harboring it.Microscopic analysis demonstrates that many plaques have no relation to
specific nerve tracts. Often, the plaques have a perivenular and paraventricular
distribution. Myelin loss from a nerve fiber is distinct and best defined by toluidine blue
stains. Macrophage accumulation is a frequent accompaniment.Active plaques contain
myelin debris. Severe loss of oligodendrocytes within MS plaques is associated with the
concomitant nonspecific finding of hypertrophic astrocytes. Signs of leptomeningeal
inflammation, not unlike that found in acute disseminated MS, may be evident.There is
also a very significant component of axonal and neuronal damage in multiple sclerosis.
This is particularly relevant to the long-term outcome and eventual disability. One can find
evidence of axonal injury early on in the disease process.This is found in areas of obvious
demyelination as well as areas of white and gray matter that appear normal to gross inspection.
It is proposed that an antigen-specific destructive component related to both T cells and
autoantibodies as well as the effects of activated macrophages and microglia lead to very
significant axonal damage in the pathogenesis of MS. Mitochondrial function may also be
impaired as various cellular substrates further contribute to this pathologic component.
Clinical subtypes
The natural history of MS varies with the subtype of disease.Functional consequences may
relate to some degree of axonal loss occurring after demyelination.
● Benign MS
● Relapsing–Remitting MS
● Secondary Progressive
● Primary Progressive
Differential diagnosis
● Because MS can affect any area of the CNS from the optic nerves to the distal spinal cord,
patients present with extremely varied manifestations occurring over a wide age range
from mid childhood into the early sixth decade. Whenever one is confronted with an acute
neurologic process primarily affecting the CNS in a previously healthy young person, the
physician must always consider if this could be the initial presentation of MS. There is a
very broad differential diagnosis predicated on the patient’s initial symptomatology.
Management and therapy
Immunomodulatory Therapy
Medical management of MS was once limited to palliative care.Although symptom treatment
remains integral to MS care,immunomodulatory therapies are changing treatment.
Pharmacologic interventions modify the course of MS through the reduction of relapse rate and
MRI lesion burden, both of which are likely to affect disease progression.Five drugs are
approved by the USFDA for treatment of
RRMS: interferon beta-1b, intramuscular interferon beta-1a,
glatiramer acetate, subcutaneous interferon beta-1a, and natalizumab infusion.
Diagnostic Approach
● Although there are no specific criteria for making the diagnosis of MS, MRI is the most
helpful diagnostic adjunct. When typical MRI findings are found in the presence of a
classic history and physical findings, there is little need to resort to other testing modalities
in most clinical settings.
● Although MRI provides a superb diagnostic testing modality, it always needs to be
accompanied by an appropriate clinical setting to make an unequivocal diagnosis of MS.
Clinicians utilize a set of consensus criteria that continually evolve as new technological
advances become available.
Thank you!..