Hyperacute experimental allergic encephalomyelitis in rhesus monkeys as a model of acute necrotizing hemorrhagic encephalomyelitis

Abstract

A comparative study of clinical and morphological findings in three fatal cases of acute necrotizing hemorrhagic encephalomyelitis (ANHE) and hyperacute experimental allergic encephalomyelitis (HEAE) in rhesus monkeys is reported. In all cases ANHE was characterized clinically by definite prodromal respiratory infection. The course was rapidly progressive with fatal termination. The salient histopathological changes were necrosis of blood vessels with plasma exudation and fibrin impregnation, hemorrhages and inflammatory reaction in the damaged cerebral tissue. Perivascular lymphoid histiocytic infiltration with glial proliferation was also noted in all cases. Numerous compound granular cells were found in one case. HEAE was detected in five rhesus monkeys immunized with homological spinal cord emulsion with complete Freund adjuvant. The illness was acute or subacute and the course was rapidly progressive with a fatal end. There was multiple necrosis of small blood vessels with plasma exudation, fibrin impregnation and massive neutrophila infiltration of the damaged brain tissue in all rhesus monkeys with HEAE. There was also widespread glial proliferation and numerous compound granular cells alongside with necrosis of blood vessels in the brain. These findings suggest that HEAE in rhesus monkeys can be viewed as an adequate model of ANHE.

Acute haemorrhagic leucoencephalitis in a Californian sea lion (Zalophus californianus )

“…The sea lion had a severe haemorrhagic encephalitis, which was not associated with the pathogenic organisms examined. The histopathological features did not resemble those of the encephalitides previously reported in marine animals, but similar findings have been described in rhesus monkeys immunised by homological spinal cord emulsions with complete Freund's adjuvant (Ravkina and others 1979). This hyperallergic encephalomyelitis was thought to be an excellent model of human AHLE (Ravkina and others 1979).…”

“…The histopathological features did not resemble those of the encephalitides previously reported in marine animals, but similar findings have been described in rhesus monkeys immunised by homological spinal cord emulsions with complete Freund's adjuvant (Ravkina and others 1979). This hyperallergic encephalomyelitis was thought to be an excellent model of human AHLE (Ravkina and others 1979). In dogs, allergic encephalomyelitis has been experimentally induced, where perivascular areas of myelin loss were detected but haemorrhage was absent (Summers and others 1984).…”

Evidence of axonal damage in human acute demyelinating diseases

“…This condition is thought to be due to an allergic or autoimmune reaction triggered by a preceding, usually respiratory, infection. This view is based on several lines of evidence: the latent period that usually elapses between the recovery from the preceding infection and onset of neurological disease; the inability to demonstrate an infective agent in the CNS, and the close similarity of the pathology to a hyperacute form of experimental allergic encephalomyelitis induced by immunizing animals with myelin or more heterogeneous CNS antigens together with pertussis vaccine [15,16]. Axon damage has been attributed to toxic mechanisms related to necrosis of the endothelium of inflamed veins and venules and with access of circulating proteins to the brain parenchyma neighboring these vessels.…”

Case 1-1999

“…In acute hemorrhagic leukoencephalitis and experimentally induced hyperacute allergic encephalomyelitis, however, the perivascular infiltrates consist mainly of polymorphonuclear cells; perivascular hemorrhages are common, and the distinctive feature is a necrotizing vasculitis of venules. [27][28][29][30][31][32][33] This similarity of features suggests that acute disseminated encephalomyelitis and acute hemorrhagic leukoencephalitis, like the corresponding animal models, are primary immune-mediated diseases. Treatments for experimentally induced allergic encephalomyelitis have been the model for developing approaches to the treatment of multiple sclerosis.…”