For several decades the unsolved etiogenetic and therapeutic problems of multiple sclerosis have offered the strongest challenge to research in neu- rology. The hope of decisive theoretical and practical progress increased when an experimental model presenting far-reaching conformity of structural and pathogenetic features was developed, namely chronic re- lapsing experimental allergic encephalomyelitis (CREAE). During the past years, Dr. Lassmann has contributed substantially to the adaptation of this model with the aim of comprehensive evaluation, thoroughly fol- lowing up his own ideas in numerous studies of individual aspects. The new possibility of continuous and detailed investigation of the clinical, morphological and immunological characteristics of temporal phase sequence of autoimmune demyelination has led to many new findings, corrections offormer hypotheses, and, from correlated studies of human multiple sclerosis, a series of important data concerning, for example, early manifestations of demyelination, the range of so-called acute mul- tiple sclerosis and the incidence of remyelination. Moreover, Dr. Lass- mann has analysed several special problems which became definable in the course of his own studies or in collaboration with other groups, in- cluding the initial distribution of demyelinated foci, the cerebrospinal fluid phenomena and immunological findings in the nervous tissue. The results of these separate studies also led to a deeper understanding of demyelinating processes. This monograph integrates these studies and summarizes their re- sults.

The present report, compares two murine models of virus induced chronic relapsing demyelination. MHV-induced demyelination in the BALB/c mouse results from the direct virus mediated cytolysis of oligodendrocytes. Extensive remyelination by oligodendrocytes is noted. Recurrent demyel- ination occurs in small areas. Infectious virus persists and 34 Fig. 2: Demyelination in SJL/J mice infected with TMEV. A) Multifocal areas of perivascular demyelination in the spinal cord (110 days post infection). Para- phenylene diamine stain. X 250. B) Perivascular inflammatory infiltration within the white matter of the spinal cord (22 days post infec- tion). Paraphenylene diamine stain. X600. C) Localization of TMEV associated antigen in the cytoplasm of oligodendrocytes (45 days post infec- tion). Vibratome section stained with the peroxidase-anti peroxidase technique. X 400. D) Immunoperoxidase staining of viral antigen within inner and outer loops of an oligodendrocyte (45 days post infectin) X 60,000. E) Longitudinal section showing viral antigen within Schmidt-Lanterman incisures (80 days post infection). X 49,000. viral antigens are localized within oligodendrocytes and their processes. TMEV-induced demyelination in SJL/J mice is asso- ciated with perivascular inflammatory infilrates and is dimin- ished by immunosuppressive measures. Remyelination by oligo- dendrocytes is delayed and incomplete. Chronic demyelination is widespread and associated with perivascular inflammatory infiltrates. The virus persists and viral antigen is local- ized within oligodendrocytes.