Mark Mumenthaler, M.D., Heinrich Mattle, M.D. Fundamentals of Neurology. – P. 156-159.
The common feature of all diseases affecting myelin is a pathological abnormality or total destruction of myelin sheaths, primarily in the central nervous system. Deficient myelin formation is caused by congenital enzyme defects in a small subgroup of these diseases (the leukodystrophies), but, in most of them, myelin is lost later in life, for reasons that are currently not well understood. Immunological (autoimmune) processes and metabolic disturbances appear to play important roles. The most common demyelinating disease is multiple sclerosis.
Multiple sclerosis (MS) is a chronic disease of the central nervous system. It usually presents with episodic neurological deficits, which, later on in the course of the disease, tend not to reverse fully, leaving increasingly severe residual deficits whose summation causes progressively severe disability.
The clinical manifestations are very diverse because widely separated areas of the CNS are affected and the temporal course of the disease is variable.
“Disseminated encephalomyelitis” is a synonym for multiple sclerosis. In French, the disease is called “sclerose en plaques,” as it was named by Charcot; related terms are used in the other Romance languages.
Epidemiology. The incidence in temperate zones is four to six new cases per 100 000 persons per year and the prevalence is greater than 100 per 100 000. MS is particularly common in northern Europe, Switzerland, Russia, the northern U.S.A., southern Canada, New Zealand, and southwest Australia. Women are affected about four times as commonly as men. The initial attack usually occurs in the second or third decade, only rarely in a child or older adult.
! After ischemic stroke, multiple sclerosis ranks second among all neurological diseases as a cause of chronic disability.
Pathological anatomy. There are disseminated foci of demyelination in the central nervous system (brain and spinal cord), sometimes with destruction of axons as well. Local, reactive gliosis is found at the sites of older foci. Thus, “sclerosis” develops at “multiple” locations, giving the disease its English name.
Pathogenesis. The pathogenetic mechanisms underlying MS are still poorly understood. The most promising hypothesis at present is that an infection of neurons and glia occurs in childhood, after which the genome of the pathogenic organism remains in the nervous system. The pathogenic genome is then reactivated on multiple occasions through influences of various kinds; this reactivation, in turn, impairs the functioning of the oligodendroglia, producing episodes of demyelination. According to this hypothesis, CNS demyelination and the generation of antibodies against myelin are merely secondary consequences of the disease process, rather than the cause of MS. An effect of the primary infection outside the central nervous system might explain the lymphocyte abnormalities that are also observed in MS.
Another hypothesis is that an infection induces a (cellmediated) autoimmune reaction against normal or virally infected components of the nervous system. In any case, multiple sclerosis clearly involves a reactive process that can be set in motion by more than one precipitating factor. This explains why foci can arise in such diverse locations in the central nervous system and why the temporal course of the disease is so variable.
Many different exogenous factors have been proposed as putative causes of MS, but no clear causal relationship has yet been demonstrated for any of them.
Course. The temporal course of multiple sclerosis (Fig. 8.1) can be characterized:
_ by the episodic appearance of new neurological deficits (relapsing type), which can then:
_ by episodic worsening at first, followed by steady progression (secondary progressive type);
_ by steady progression from the beginning (primary progressive type), as is most commonly seen in older patients with paraparesis; or
_ by steady progression with interspersed episodes of acute worsening (progressive relapsing type).
Clinical manifestations and neurological findings. The general clinical features of MS are summarized in Table 8.1.
The neurological deficits present in each individual patient depend on the number and location of the demyelinating foci. The following are among the more characteristic disease manifestations and physical findings: