Experimental allergic encephalomyelitis (EAE) has been used for years as an experimental model of MS. It can be induced in mice, rats and guinea pigs by intradermal injection of whole CNS tissue or myelin basic protein (MBP). Two weeks after the injection, the experimental animals develop ascending paralysis. The injection of MBP triggers a cell-mediated immune reaction against the recipient's myelin. MBP-specific T-cells traverse brain capillaries. Interaction of these cells with MBP activates them and results in secretion of cytokines, damage of the blood-brain barrier, and recruitment of macrophages. Microscopical examination shows perivenular lymphocytes, similar to acute MS, but little or no demyelination. EAE can be induced by injection of MBP-specific T-cells. Classic EAE is a monophasic reaction. A chronic relapsing EAE has been induced in guinea pigs. EAE can also be induced by other myelin proteins that are chemically different from MBP, and by nonmyelin proteins such as S100 protein. Injection of MOG (myelin oligodendrocyte glycoprotein) along with transfer of anti-MOG lymphocytes can cause demyelination. While EAE proves that an autoimmune reaction can cause inflammation in the white matter, the analogy with MS stops there. The immunology and pathology of MS are far more complex than EAE.

ACUTE DISSEMINATED ENCEPHALOMYELITIS

ADEM ADEM. Multiple demyelinative lesions.

ADEM ADEM. Multiple demyelinative lesions.

Acute disseminated encephalomyelitis (ADEM), also known as postinfectious, postvaccinal, or allergic encephalomyelitis, is an acute demyelinating disease, which most commonly affects children. It develops usually a few days to four weeks following a nonspecific upper respiratory infection or after infection with a variety of other viral and bacterial agents, including Epstein-Barr virus, cytomegalovirus, or mycoplasma pneumoniae, and following vaccinations. Sometimes it appears without a preceding infection. After an initial phase characterized by malaise, fever, headache, stiff neck, and drowsiness, multifocal deficits (hemiplegia, ataxia, sensory abnormalities, visual loss) appear within hours or a few days. Ataxia is especially common in ADEM following varicella. The MRI shows multiple bilateral hyperintense lesions in the centrum semiovale and deep nuclei. Some large confluent lesions resemble brain tumors because of perilesional edema and mass effect. Most ADEM cases are monophasic and have a favorable outcome, especially after treatment with high dose IV corticosteroids. However, a few cases are severe or even fatal.

Pathologically, ADEM is characterized by perivenous inflammation (T- lymphocytes and macrophages), demyelination, and axonal loss. Acute hemorrhagic leukoencephalitis (Weston-Hurst syndrome) is a fulminant, frequently fatal form of ADEM with extensive, confluent white matter lesions, characterized by vascular necrosis, acute inflammation, hemorrhage, and edema.

ADEM is not an infection. It is thought to be a T-cell mediated immune reaction triggered by the preceding viral infection or vaccination. Similarity between viral and myelin proteins probably accounts for some ADEM cases. In this scenario, sensitized T-cells attack not only the pathogen but also neural tissues that contain similar proteins. Rabies vaccines prepared from brains of inoculated sheep are contaminated with CNS tissue. ADEM following such vaccination is analogous to EAE. It is due to sensitization against myelin antigens that are present in the vaccine. Alternatively, CNS tissue and vascular damage that occur in the course of some infections exposes CNS (myelin) antigens to the immune system. Autoreactive T-cells, generated in this process invade the brain and destroy myelin.