relatively mild viral diseases. These are not thought to be related to direct spread of the infectious agents to the nervous system. Rather, it is believed that immune cells responding to pathogen-associated antigens cross-react against myelin antigens, resulting in myelin damage.
There are two general patterns of postinfectious autoimmune reactions to myelin; unlike MS, they both are associated with acute-onset monophasic illnesses. In acute disseminated encephalomyelitis, symptoms typically develop 1 or 2 weeks after an antecedent infection and are nonlocalizing (headache, lethargy, and coma), in contrast with the focal findings of MS. Symptoms progress rapidly, and the illness is fatal in as many as 20% of cases; in the remaining patients, there is complete recovery. Acute necrotizing hemorrhagic encephalomyelitis is a more devastating related disorder, which typically affects young adults and children.
Other acquired diseases of myelin include neuromyelitis optica (NMO), an antibody-mediated demyelinating disease centered on the optic nerves and spinal cord, and central pontine myelinolysis, caused by nonimmune damage to oligodendrocytes typically after sudden correction of hyponatremia, that may result in a rapidly evolving quadriplegia.
As discussed earlier, progressive multifocal leukoencephalopathy (PML) is a demyelinating disease that occurs after reactivation of the JC virus in immunosuppressed patients.
Leukodystrophies are inherited dysmyelinating diseases caused by abnormal myelin synthesis or turnover. They are caused by mutations of genes whose products are involved in the generation, turnover, or maintenance of myelin. Some of these mutations affect lysosomal enzymes, while others involve peroxisomal enzymes; a few are associated with mutations in myelin proteins. Most are of autosomal recessive inheritance, although X-linked diseases also occur. There is typically diffuse involvement of white matter leading to deterioration in motor skills, spasticity, hypotonia, or ataxia. Several clinical features separate leukodystrophies from demyelinating diseases. The leukodystrophies typically present with an insidious and progressive loss of function, often begin at younger ages, and are associated with diffuse and symmetric changes on imaging studies.
MORPHOLOGYMuchofthepathologicchangeofleukodystrophyisfoundinthewhitematter,whichisdiffuselyabnormalincolor(grayandtranslucent)andvolume(decreased).Earlyintheircourse,somediseasesmayshowpatchyinvolvement,whileothershaveapredilectionforoccipitallobeinvolvement.Intheend,though,nearlyallofthewhitematterusuallyisaffected.Withthelossofwhitematter,thebrainbecomesatrophic,theventriclesenlarge,andsecondarychangescanbefoundinthegraymatter.Myelinlossisassociatedwithinfiltrationofmacrophages,whichoftenbecomestuffedwithlipid.Someofthesediseasesalsoshowspecificinclusionscreatedbytheaccumulationofparticularlipids.
Becauseofthecriticalroleofmyelininnerveconduction,diseasesofmyelincanleadtowidespreadandsevereneurologicdeficits.
Multiplesclerosis,anautoimmunedemyelinatingdisease,isthemostcommondisorderofmyelin,affectingyoungadults.Itoftenpursuesarelapsing-remittingcourse,witheventualprogressiveaccumulationofneurologicdeficits.
Other,lesscommonformsofimmune-mediateddemyelinationoftenfollowinfectionsandaremoreacuteillnesses.
Leukodystrophiesaregeneticdisordersinwhichmyelinproductionorturnoverisabnormal.
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