Chronic relapsing EAE time course of neurological symptoms and pathology

Summary

The inflammatory reaction in chronic relapsing EAE was studied with special reference to the alterations found in the early stages of the disease (first attack, first remission, and first relapse). The inflammatory reaction during the early stages of the first attack was dominated by polymorphonuclear leukocytes, together with edema and sometimes hemorrhage, resembling the alterations found in hyperacute or neutrophilic EAE. The tissue reaction consisted of myelin, as well as axonal damage, and involved predominately the root entry zones and the subpial white matter in the lower thoracic and lumbo-sacral spinal cord, with less severe damage in grey and white matter in other regions of the brain. During the first remission, a variable amount of perivascular inflammatory cuffs of lymphocytes and mononuclear cells were found, but cellular infiltration into the neural parenchyma was confined to a few small perivascular areas. In the first relapse, a massive invasion of the neural parenchyma by mononuclear cells was noted, leading to large plaque-like zones of demyelination in the white matter. In this stage of the disease axonal damage was rare. The lesions were predominantly confined to the lower thoracic and lumbo-sacral spinal cord, but with increasing duration of the disease, higher portions of the spinal cord, as well as brain stem, cerebellar white matter, centrum semiovale and fornix were involved, too.

Further relapses showed a similar pattern as described in the second attack, although in these animals lesions of different ages were always found. Parallel with the clinical observations, the inflammatory reaction in the central nervous system also diminished with the duration of the disease.

A comparison between Strain 13 and Hartley guinea pigs revealed a more severe reaction during the first attack in the latter, possibly responsible for the high mortality of these animals during this stage of the disease.