19
One would naturally anticipate . that, if the symptoms of the disease are due to the immediate
influence of the bodies on the brain cells, they would be demonstrable concurrently with its
outbreak, and. one as naturally regards the bodies as organisms spreading from a centre and
gaining in size until they have multiplied sufficiently to interfere with the vital activity of a large
proportion of the cells of the central nervous system, when paralysis begins.
The possibility of finding Negri bodies two days before the appearance of any symptoms, which
we have just described, only holds good for subdural infections. It is by no means easy to prove
what happens in natural, cutaneous infection, even when it occurs under supervision, on account
of the variability of the incubation period ; but analogy would lead one to suppose that microscopic
changes would be evident in the brain before the cell destruction had reached a sufficient pitch for
such a gross symptom as motor weakness to be detected. That the first symptoms are due to an
invasion of the cells of certain parts of the central nervous system, depending entirely on the
locality of the point of infection, and not to a toxin manufactured by the organism which has a
.specific action on nerve cells in general is, we think, made quite clear by the microscopic findings
in the following case.
A rabbit which had been inoculated with street virus from guinea pig No. 5 (see Table 7) in its
left sciatic nerve displayed weakness of the hind legs on the 11th day and was killed on the 12th
day and the parts sectioned. The medullated sheaths of the fibres of both sciatic nerves were
broken up and the axis cylinders of many fibres were entirely disorganised.
In the lumbar spinal cord. there was considerable cell exudation round some of the blood
vessels. Few unchanged nerve cells could be seen, but no Negri bodies. In some of the cells of
the posterior root ganglia in the lumbar region small Negri bodies were plentiful, other of the
cells were in process of being replaced. by invading leucocytes. The bladder was enormously
distended but the urine was not tested for sugar.
No Negri bodies were to be found in the cervical spinal cord, but there were degenerative
changes in the cells of the anterior horn and small hæmorrhages. No Negri bodies were visible
in the hippocampus major.
Here we have a distribution of the injuring agent corresponding to its position of entry into
the body. The pathological changes were most intense in the region nearest the original focus
of infection and became less marked the further off one looked.
Unfortunately in the series set forth in table 10 the lumbar spinal ganglia were not
sectioned, so we cannot say at what period Negri bodies reached the lower end of the cord, but
on the day the bodies were first seen in the hippocampus the cervical. ganglia were still free, so it
is fair to assume that the lumbar ganglia were not involved until later.
This case might afford ground for a modification of the view we expressed in commenting
-on table 10, that in natural rabies one would expect to be able to detect Negri bodies in the
brain before they have developed sufficiently to cause gross symptoms, were it not that even here
natural conditions are not by any means exactly reproduced, since not only was .the infective
dose larger than would be probable in nature, but also brain substance conveyed the organism
and not saliva, possibly in another stage of its life history.
It does not necessarily follow, therefore, that Negri bodies will be found in the brain of a
dog two or three days before the outbreak of natural rabies, though it is to be confidently ex-
pected that they Will. Nor does it follow because Negri bodies cannot be found in the early stages
of artificial rabies at the end of the spinal column furthest from the point of their introduction
that that portion of the nervous system is still free from disease and. non-infective. Indeed. the
. fact that the saliva has by several workers been proved to be capable of conveying rabies in
nature several days before the appearance of symptoms would go to show that the infective agent
has already spread itself widely in some guise or other.
Negri bodies have so far been found only in the cells of the central nervous system. They
cannot be recognised in the peripheral nerves nor in any organ in spite of the fact that the peri-
pheral nerves and the salivary glands are frequently capable of conveying the infection, and the
pancreas, adrenals and possibly other parts more seldom.
Stephanescu (28), however, has recently recorded the discovery of Negri bodies in the
secreting cells of the parotid of a rabid dog and von Babes, who examined her preparations,
confirmed the observation, noticing also similar bodies of various sizes in the lumen of a duct,
Without denying the merit of this discovery it is as well to mention that we have carefully
scrutinised the salivary glands in the few cases of natural rabies we have been able to secure and
also in a good many artificial infections with both street and fixed virus without coming across
.any undoubted Negri bodies even when the glands were proved to be infective.
We did find that Negri bodies were closely simulated in several instances by droplets of
secretion in the cells which take the eosin stain. The similarity was sometimes rendered even more
-marked by the occasional appearance of structure within the droplets, even to the formation of a