Encephalitis or meningoencephalitis is a rare complication (15 per million) of vaccinia (smallpox vaccination). It has been reported among vaccinees in the U.S. and many other countries, but how many are coincidental in time and how many are related to the vaccination itself is impossible to know. A number of different infectious agents and non-infectious processes can be responsible and it is often impossible to establish the etiology.

In general, this is a severe disease with high mortality and morbidity. European data indicate a higher incidence than in the U.S., but whether this reflects the use of different vaccine strains or differences in diagnostic methods is unknown. There are no known predictive antecedents.

The mechanisms for this form of encephalitis are unknown. Various hypotheses have been advanced but the one that is deemed most likely is that it represents an autoimmune process. Midbrain, cerebral and medullary lesions have been observed, and in one-fifth of the cases myelitis is predominant. Increases in CSF pressure, CSF lymphocytosis, and increases in CSF protein content all represent non-specific findings. 

One-third of all cases have proved fatal and half of all survivors have had some residual neurologic defect, ranging from a convulsive disorder to profound neurologic deficit. Many patients recover completely without discernible residua.