Irrespective of the clinical setting in which it occurs, disseminated encephalomyelitis in its severe form is of grave import because of the significant rate of neurologic defects in patients who survive. In children, recovery from the acute stage is sometimes followed by a permanent disorder of behavior, developmental delay, or epilepsy but there are many exceptions in milder disease; paradoxically, most adults make good recoveries. The cerebellitis and acute ataxia that follow chickenpox and other infections are more benign, normally clearing over several months, and may represent a different process, as discussed further on.
The pathogenesis of disseminated encephalomyelitis is still unclear despite its obvious association with preceding viral infections. In the postexanthem cases, a definite interval usually separates the onset of disseminated encephalomyelitis from the onset of the rash; also, the pathologic changes are quite different from those of viral infections and virus is rarely if ever recovered from the CSF or brains of patients with disseminated encephalomyelitis. For these reasons, it is believed that the disorder represents an immune-mediated complication of infection rather than a direct infection of the CNS, a process comparable to the Guillain-Barré syndrome. However, as discussed in Chap. 32, new molecular techniques have been used to detect fragments of DNA from varicella zoster virus, Mycoplasma, and other organisms in the CSF, so that the question of pathogenesis cannot be answered with finality. Nevertheless, Waksman and Adams found the pathologic changes in these 2 circumstances—postinfectious demyelination and direct viral infection of the CNS—to be quite different.
A laboratory model of the disease, EAE, has been produced by inoculating animals with a combination of sterile brain tissue and adjuvants. The experimental disease appears most commonly between the 8th and 15th days after sensitization (see in the following text) and is characterized by the same perivenular demyelinating and inflammatory lesions that one observes in the human disease. Presumably the lesions are the result of a T-cell–mediated immune reaction to components of myelin or oligodendrocytes. Evidence of antibody binding, complement activation, and eosinophilic infiltration has led to the notion that ADEM is a humoral disorder, in contrast to the cellular mechanism that has been proposed for MS, but confirmation of this notion is required (see
Lucchinetti et al, 2000 and 2002). Furthermore, a proportion of cases display the earlier mentioned anti-MOG antibody; however, the titer of these antibodies drops rapidly after the onset of the acute attack, making their role in pathogenesis uncertain.
The notion that EAE and disseminated encephalomyelitis have a similar pathogenesis received support from the observations of R.T. Johnson and colleagues. They studied 19 patients with postinfectious encephalomyelitis complicating natural measles virus infections. Early myelin destruction was demonstrated by the presence of MBP in the CSF, and lymphocyte proliferative responses to MBP were found in 8 of 17 patients tested. Similar responses were observed in patients with encephalomyelitis after rabies vaccine and after varicella and rubella virus infections, suggesting a common immune-mediated pathogenesis. Moreover, the patients with postmeasles encephalomyelitis showed a lack of intrathecal synthesis of antibody against measles virus, indicating that the neurologic disease was not dependent on viral replication within the CNS.