Posted by: Thixia | March 5, 2008

Multiple Sclerosis: A Progressive Disease Part 1

Multiple Sclerosis: A Progressive Disease Part 1

Background
Multiple sclerosis (MS) is a progressive disease that attacks the CNS and affects multiple systems of the body through attacks on the nervous system. MS affects individuals of all races and socioeconomic groups and is seen all over the world. It is most common in white women of northern European descent. The initiating event is unknown, but a great deal of progress has been made in understanding the pathophysiology and treatment of the disease. This article discusses the epidemiology, pathophysiology, signs and symptoms, diagnosis, treatments, and outlook for the future for patients with MS.

Pathophysiology

MS is an immune-mediated inflammatory disease that attacks myelinated axons in the CNS, destroying both the myelin and the axon in variable degrees. The disease is characterized initially by episodes of reversible neurologic deficits, which, in most patients, are followed by progressive neurologic deterioration over time. The cause of the disease is not known, but it likely involves a combination of genetic susceptibility and an environmental trigger, resulting in a self-sustaining autoimmune disorder that leads to recurrent immune attacks on the CNS.

MS is currently believed to be an immune-mediated disorder with an initial trigger, which may have a viral etiology (cause or origin), although this concept has been debated for years. Identification of a single virus has not been successful to date, despite ongoing efforts worldwide. In fact, no evidence exists that MS is

contagious. Multiple viruses may initiate an immune reaction that cross-reacts with a neural antigen (eg, myelin antigens), which Talbot has called molecular mimicry. This cross-reaction may then lead to injury of the myelinated CNS axons and oligodrocytes and neurons. The oligodendrocyte is responsible for producing the protective myelin sheath surrounding the axon in the CNS and may be particularly susceptible to the immune attack. CNS infections may also lead to the transmigration of activated T lymphocytes into the CNS, which may be sufficient to initiate the autoimmune process in genetically susceptible individuals. However, the pathogenesis remains incompletely understood.

Examination of the demyelinating lesions, called plaques, in the spinal cords and brains of patients with MS shows myelin loss, destruction of oligodendrocytes, and reactive astrogliosis, often with relative sparing of the axon cylinder. However, some in some MS patients, the axon is also aggressively destroyed. These active lesions show breakdown of the blood-brain barrier with penetration of leukocytes. A combination of T cells, B cells, and macrophages is believed to be responsible for the attack on the myelin antigens. The location of lesions in the CNS dictates the type of deficit that results. As the inflammation resolves, some remyelination occurs, but most recovery of function that occurs in a patient may be due to cortical reorganization.
MS has traditionally been thought to be silent between relapses. However, MRI studies beginning in the 1980s have demonstrated that inflammatory events are occurring in the brain at 10-20 times the predicted rate indicated by the mean relapse rate. This silent disease activity is associated with cerebral atrophy, which, in most patients, is evident in volumetric studies even at diagnosis.

The initial phase of the disease is characterized by relapsing attacks of neurological disability believed to be caused by demyelination with some axonal injury, followed by partial or complete neurological recovery. This stage of the disease is called relapsing-remitting MS. As the lesion burden increases with continued relapses, patients tend to enter a phase in which relapses become less common but a slow, progressive loss of neurological function ensues. This is referred to as the secondary progressive phase of the disease and does not seem to be responsive to currently available disease-modifying agents, unlike the earlier relapsing phase. The exact mechanism of the secondary progressive phase of the disease is not known but is suggested to be due to ongoing neural degeneration. Of MS patients, 10-15% have no relapsing phase; symptoms are slowly progressive from the beginning. This form of MS is called primary progressive MS.

Frequency

Worldwide, approximately 1.1 million people are affected.

Mortality/Morbidity

Life expectancy is shortened only slightly with MS, and the survival rate is linked to disability. Usually, death is due to secondary complications (50-66%), such as pulmonary or renal causes, suicide, primary complications, and causes other than MS seen in the general population.

Race

MS is seen in all parts of the world and in all races, but whites of northern European descent have the highest incidence.

Sex
The female-to-male ratio is 2:1.

Age

The disease is usually diagnosed in persons aged 15-45 years; however, it can occur in persons of any age. The average age at diagnosis is 29 years in women and 31 years in men.

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