Some observations on the pathogenesis of eastern equine encephalomyelitis and louping-ill in young and old animals, with special reference to routes of entry of the viruses into the nervous system

Abstract

Summary Young animals infected intramuscularly with Eastern equine encephalomyelitis or louping-ill develop encephalitis sooner and die in far larger numbers than do older animals. Thus with equine encephalomyelitis 92 per cent. of three-week-old mice died by the 7th day, and only 18·6 per cent. of adult mice by the 8th day. With louping-ill 100 per cent. of two-week-old mice died by the 9th day, and only 41·8 per cent. of old mice by the 18th day. The transition between the greater susceptibility of young animals and the lower susceptibility of old animals is gradual. The difference in response of young and old animals can probably be attributed to a greater susceptibility of the cerebral tissues (ten-fold in the case of equine encephalomyelitis, a hundred-fold in the case of louping-ill), combined with the fact that virus multiplies more and circulates longer in the blood of the young. There is no evidence that hormonal factors play a part. With these two viruses no absolute difference exists in the route by which the nervous system is invaded in young and old animals. Neither virus commonly spreads by way of the peripheral nerves. There remain as alternatives (i) spread by the blood-stream, and (ii) infection by way of the nasal mucosa and olfactory apparatus. The difficulty in reaching a decision as to the route followed in the case of equine encephalomyelitis is discussed; no conclusive evidence in favour of the second alternative has been adduced. In louping-ill, on the other hand, the evidence suggests that either or both routes may be used according to circumstances. In louping-ill in old mice the nervous infection may be localised and arrested in the olfactory bulbs. Removal of the olfactory bulbs does not prevent infection of the nervous system with virus given intramuscularly; on the contrary it may enhance susceptibility both to intramuscularly and to intracerebrally injected virus. Same measures reputed to increase the passage of chemical substances from blood to brain do not alter the incidence of nervous involvement in equine encephalomyelitis or louping-ill. The development of encephalomyelitis in louping-ill is favoured when, during the period in which virus circulates in the blood, the animals are exposed to coal-gas or subjected to insulin-shock. These measures have no effect in equine encephalomyelitis, in which disease, however, the intravenous administration of adrenalin-andpituitrin tends to increase the number of cases of encephalitis and expedite their appearance in old animals only. It is probably incorrect to use the term “permeability” in relation to the passage of viruses from blood to brain; the transit is here regarded as a “growth through” the wall of the vessel. When a mouse, guinea-pig or rabbit escapes encephalitis after peripheral inoculation of the virus of equine encephalomyelitis, it does so because virus has not reached the nervous system and not because it has suffered an inapparent nervous infection. In loupingill cases of subclinical involvement of the nervous system are seen occasionally.