ful peripheral inoculation of rabbits with a strongly neurotropic tribution of a particular nerve the

18 Pages·2007·1.6 MB·English

THE PATHWAYS OF INFECION OF THEE CENTRAL NERVOUS
SYSTEM IN HERPETIC ENCEPHALITIS OF RABBITS CON-
TRACTED BY CONTACT; WITH A COMPARATIVE
COMMENT ON MDULLARY LESIONS IN A
CASE OF HUMAN POLIOMYELITIS*
ERET W. GOODPASTURE
(Fromah WilimH.SixgerMemoialRechLaboratory,AleghenyGeneralHosp",
Pitrgh,Penusyhania)
PART I
Theinitiallesioninthecentralnervoussystemfollowingasuccess-
ful peripheral inoculation of rabbits with a strongly neurotropic
strain (Strain M) of the virus of herpes simplex is so definitely re-
lated to thenerve supplying the inoculated area and its central ter-
minaton,1 that given suitable sections of a brain thus infected it is
possible for one to determine not only by which nerve the virus
gained entrance, but in certain instances in what peripheral dis-
tribution of a particular nerve the originalinfection was located.
By a studyof the brain and spinal cord with particular reference
to the entrance and central distribution of the cranial and spinal
nerves it was thought possible to determine with certainty in this
manner the mode of entrance of the virus in cases of contact infec-
tion,shouldrabbits acquireaherpeticencephalitis throughexposure
to an infected ani
Normal rabbitsproved tobeverysusceptible to contactinfection
with Strain M virus and ahighper centof those placedin the same
cages with rabbits inoculated upon the cornea contracted in a few
days a herpetic encephalitis. The first evidence of an infection of
thebrainwas an elevationof thebody temperature. A few animals
were permitted to die of the disease and these for the most part
showed much the same symptoms without evidence of a unilateral
cerebral lesion.
When the body temperature first became elevated there were no
otherindicationsofdisease. Inthecourseofadayortwo, however,
there developed muscular weakness and tremors assocated with a
* ReceivedforpublictionJuly I2,1924.
29
30 GOODPASTURE
rathergeneral clonic contraction ofmuscles. One anima turned its
head to the right, in others the head was periodically drawn back-
ward asin opisthotonos. Thesesymptomswererapidlyfollowedby
an apparent loss of equilibrium, weakness, convulsions and death.
Itisprobable thatalargepercentifnotallofouranimals thatcon-
tracted herpetic encephalitis would have died of the disease in a
short time though the mortality rate was not determined.
Ininvestigating thepathsofentranceof thevirusintothecentral
nervoussystemitwasdesirable toexamine thebrainverysoonafter
thevirusenteredandbeforelesionsotherthan those assocatedwith
the nerve through which the virus was admitted had developed to
any great extent.
Experience with herpetic encephalitis following peripheral inocu-
lation and infection had made it appear most certain thatin an en-
cephalitis induced through infection by contact the virus would
enter the brain in the same manner, thatis, along the course of one
or more of the peripheral and probably the cranial nerves. With
this in mind most of the animals in these experiments were killed
from one to four days after the first elevation of body temperature,
and the brains fixed mmediately after exsanguinaton by injecting
Helly's fluid through the carotid arteries. The brain and spinal
cord were then removed in toto and the fixation continued for 24
hours in an ample amount of the same fluid. After washing,
blocks including an entire cross section of the brain were cut from
the olfactory and frontal lobes, the mid-cerebrum through the in-
fundibulum, midbrain, pons, medulla and spinal cord at various
levels. Microscopic sections soon revealed the two localities where
herpetic lesions were to be expected, that is, at the entrance of the
fifth cranial nerves in the pons and the ninth or glossopharyngeal
nervesinthemedulla. Insucceedingexperimentsinaddition tosec-
tions from the above-mentioned regions, serial sections were made
including intraduralportions of thefifth and ninth nerves and their
entire sites of entrance and distnbution in the brain.
In thiswayit has been possible to showthat in herpetic enceph-
alitis contracted through contact, bilateral herpetic lesions occur
at the central terminations of one or both of these nerves, usually
more marked onone side. In the case of the sensorydivisionof the
fifth nerve, lesions could be demonstrated within the nerve central
to theplane where the sheaths of Schwann disappear and before its
PATHWAYS OF INFECTION OF THE CENTRAL NERVOUS SYSTEM 31
entrance into the brain, as was likewise the case following inocula-
dons of the cornea. However, in the spontaneous or contact infec-
tions, the lesion involved a different portion of the nerve, affecting
fibers in thedorsal third, whereas following herpeticinfectionof the
cornea the ventral portion of the nerve contained the lesion. This
relation was also preserved in the descending crescentic tract, the
lesion in contactinfections occupying the dorsal horn as the bundle
of fibers coursed through the medulla.
Intwoinstances therewasalesioninorattheterminationofthat
group of fibers which enters with the motor division of the fifth
canial nerve and arises from the unipolarganglion cells situated at
thelateralanglesofthefloorofthefourthventricle, constitutingthe
mesencephalic or accessory fifth motor nucleus. In one of these
cases in which no lesion was present in the corresponding sensory
divisionofthenervetherewasnomeningits atitspointofentrance.
In all the other cases there was an acute meningitis at the entrance
ofthefifthorninthnervesorboth, aswellasanexudateinthebrain
along theirdistnbution. In those instanceswhere theglossopharyn-
geal nerves were involved destructive lesions were found in the
medulla restricted to the course of these fibers within the medulla
andin the corresponding nucleiin the floorof the fourth ventricle.
In earlier stages of the lesions intranuclear herpetic bodies, espe-
dally within neuroglia cells, are very numerous, and there is an
associated necrosis of cells with many pyknotic nuclear fragments,
and a cellular exudate in which polymorphonuclear leucocytes are
prominent. Inthemeningesatthisstage thereisusuallyinaddition
to cellular exudate, fibrin and red blood corpuscles. Fibrinous and
hemorrhagic exudate may also be a part of the lesion within the
brain.
In each instance it was possible clearly to assocate the lesions
found with the fifth or ninth cranial nerve. In one brain in which
virus evidently entered through the sensory division of the fifth
nerve, there was a question as to the origin of an acute herpetic le-
sion which was found at the site of entrance of one of the glosso-
pharyngeal nerves. Itwas notpossible todetermine with certainty
whetherthelatterwasdue tovirusenteringthrough theninth nerve
or to an extension of the infection outward along this nerve from a
descending lesion in the sensory tract of the fifth nerve. The cause
of cnfusion was due to the fact that in herpetic encephalitis con-
32 GOODPASTURRE
tracted through contact in which virus enters through the sensory
division of the fifth cranial nerve the lesion in the nerve and in its
descending tract occupies a dorsal position and passes through the
medulla onalevelwith the ninthnerve asitenters, and onlyathin
layer of fibers of the Tractus spino-cerebellaris dorsalis2 separates
them from the periphery. However, when virus enters distinctly
through the ninth nerve there is not only aperipheral lesion about
the fibers of this nerve, but also a well-marked lesion in the cor-
responding nudeus at the floor of the fourth ventride.
In later stages of the infection herpetic inclusions in the lesions
at the site ofentrancewererare ornotfound atall, the conspicuous
featurebeingthelargenumberofphagocyticmononuclearcellscon-
taining vacuoles in their cytoplasm indicating a removal of degene-
rated myelin sheaths. The initial lesions tend to heal in this way,
thoughthevirusextends rapidly to thebase of the cerebrum, where
its earlier stages of activity may be seen in the cells of the Area
praesubicularis of the Lobus piriforrmis as in R. 221.
In noinstance has alesion in the olfactory lobes been found, and
i this series of experiments the olfactory nerves may be entirely
excluded from consideration as aportal of entry for the virus.
In most of the following experiments serial sections were made
through the entrance of the fifth and ninth cranial nerves.
Expaixen i.
R I82. Adultmale.
4/17. Placedincagewith R. 260 (Herpesbotheyes).
4/19. Temp. 103.30F.
4/20. 103
.
4/21. 1030.
4/22. I03
4/23. a 102.4.
4/24. a 104.2°. On right side of tongue is an irregular ulcerated area
about 5 mm. in diameter. Saliva inoculated upon scarifiedright cor-
neaof R. 273.
4/25. Temp. 103.70F.
4/26. I0340
4/27. £
4/28. Ii00.5°. Verysickandweak. Unsteadyequihbrium,difficultyin
breathing. Died i P.M.
Autopsy negative. Brain shows a maaoscopic hemorrhage in medulla
onrightside. Lesionontonguehealed.
R. 273. Half-grownrabbit.
4/25. Right corneascarifiedandinoculatedwithsalivafrom R. I82.
PATHWAYS OF INFECTION OF TE CENTRAL NERVOUS SYSTEM 33
4/28. Right eye greatly inflamed and closed with pus. Herpetic kerato-
conjunctivitis.
4/30. Headturingtoright,partiallossofequilibrum. Herpeticencephalitis.
5/4. Recovering.
Pons.
Serial sedions throughentrance offifthcranial nser. On the right side just
mediantotheplaneatwhichthesheathsofSchwannarelostandinvolvingthe
dorsalonethirdoftherootthereisalargeareaofnecrosisandcellularinfiltra-
tioninthesensorybundleofthefifthnervebeforeitentersthebrain. Thepre-
domninantcellintheexudateisthelargemononuclearphagocyticcellfilledwith
samall vacuoles. Abouttheenteringnervethereisacellularexudateintheme-
ninges consisting chiefly of mononudears, though containing an appreciable
numberofpolymorphonudearleucocytes. Theportionofthenervecontaining
sheaths of Schwann shows no change, and the motor root appears normal
throughout. Bloodvesselswithintheponsintheneighborhoodoftheentering
nervepresentathinperivascularexudateofmononuclearcells.
Ontheleft sidethereisasimilarlesionoccupyingthecorrespondingportion
of the sensory root on this side, though the extent of injury is considerably
ller. There is a localmeningitisover the area of injury, and amoderate
perivascularinfiltrationintheneighboringpons.
Thepyramidaltractsonbothsides,butmoreconspicuouslyontheright,are
clearandthefibersappearvacuolatedwhileneurogliacellscontainintranudear
herpeticbodies.
Medulla. On the right side occupying the dorsal portion of the descending
bundleofsensoryfibersofthefifthcranialnerveisalargeareaofnecrosiswith
much hemorrhage and cellular infiltration, by both large mononuclear phag-
ocytes and polymorphonudear leucocytes. The lesion extends through to the
lateral surfaceon this side andthere is acellular andfibrinousexudate in the
meninges. Thenucleusoftheglossopharyngealnerveisnotinvolved. Thereis
asmalllesionhavingasimilarsituationinthefifthsensorytractontheleftside
andaslightperivascularexudateonthisside.
There is a cellular exudate in the meninges over the ventral surface of the
medullaand aperivascular infiltration about vesselsdipping into the cerebral
tissue.
In this case the virus entered the pons through the sensory portionof both
fifth cranialnervesandextendeddownwardbilaterallyinto themedullainthe
sensorvtracts. Incontrastwiththelesionofthistractfollowinginoculationof
thecorneathelesionissituatedintheupperpoleofthecrescentictract, andin
thedorsalportionofthenerverootbeforeitenters thebrain.
Theabsenceofinvolvementoftheregionoftheglossopharyngealnucleusex-
cludesanyprobableentranceofvirusthrough thisnerve.
Experiment 2.
R. 22I. Adult rabbit.
3/20. Placedincagewith R. 219 (Herpes righteye, inoculated3/19).
3/21. Temp. I02.5 F.
3/24. Temp. 1030.
3/28. Temp. 105.I°. Nervous and shaky. Rapid rration. Nose, mouth
andeyesnegative.
34 GOODPASTIJRE
3/29. Temp. Io4.5°. Holdsheadtoright.
3/3I. Temp.I105.3°. Holdsheadtoright. Bloodydischargefromrectum. Has
lost considerable weight, salivated. Etherized. Autopsy showed acute
intersusception of rectum. There are small hemorrhages superficially
alongthemedullaontherightside.
Pons.
Serialsectionsthroughtheponsattheentranceofthefifthcranialnerveshow
nolesionin the nerveon either side. There is slight cellular infiltration about
the lateral surfacesof the floor of the fourth ventricle and slight perivascular
infiltration. This area of inflammation on either side involves the accessory
motornucleusofthefifthnerve. No herpetic indusionsfound.
There is an acutelesion along certain fibersof the right motorbundle char-
acterizedbyedemaandcellularinfiltrationwithlargephagocyticmononuclears
containingsmallvacuoles. Thisoccursfirstaboutoppositethemainmotornu-
cleusandthecellularinfiltrationextendsupwardtoagroupofcellsattheangle
ofthefloorofthefourthventride. Thereisalessercellularinfiltration similar
indistributionontheleft. Themainmotornucleuswithitsmultipolarganglion
cellsisnotinvolvedoneithersideexcept formoderateperivascularinfiltration
on theright. No herpeticinclusionsareobserved, though theacutenessof the
lesion andits generalappearanceindicateits herpeticorigin.
Section of the medullaon alevel with the entranceof the glossopharyngeal
nerveshowsatthepointofentranceofthisnerveontherightsidealargeacute
destructive herpeticlesion with necrosis, hemorrhage, and cellularinfiltration.
Largemononuclearphagocytescontainingvacuolespredominate, though there
are many polymorphonuclearleucocytes. Thislesionextendsinward anddor-
sally across the fifth sensory tract for a considerable distance along the course
oftheninth nerve, thefibersofwhich aredestroyed. Thereisaninterruption
of themassive destruction separating the moreperipherallesionfrom the area
oftheninth andtenthnucleilaterallyatthefloorofthefourthventricle. This
areashows awidespreadbut circumscribed destructivelesion. The entire area
stains lightly and there is destruction within it of nerve fibers and neuroglia,
most of the ganglion cells escaping. An abundant cellular exudate is present
consisting for the mostpart oflarge mononuclear phagocytes. There is also a
thick mantleofmononuclearcellsabout thebloodvessels.
Ontheleftsideinthesamesectionsthereisalesionofthesamedistribution
though not so extensiveanddestructive.
Serialsectionsanteriortothisregionshow a continuationof theareaofnec-
rosis and infiltration at the floor of the fourth ventricle but becoming smaller
andmoredeeplysituated. Itcomestolieratherdeeplyinthemedullaandmore
laterally, finally disappearing altogether further anteriorly. There is no evi-
denceofaprimarylesionin the descending tractsof thefifthnerve.
Posteriorlyfromthepointofentranceoftheninthcranialnerve,thelesionat
the floorofthe fourthventride extendsthroughoutthelimitsof the tenth nu-
cleus, but diminishingin severity.
Thesectionsindicatethatthevirusenteredthebraininthiscaseprncipally
ifnot altogether alongtheglossopharyngealnervesproducing alesion at their
entrance andinvolvingthenucleioftheninthandtenthnervesonboth sides.
In the previous sections thelesionsarelargelyin astateofrepairbyphago-
cytosis.
Cerebrum through the infundtibuium. Sections through the cerebrum on a
PATHWAYS OF INFECTION OF THE CENTRAL NERVOUS SYSTEM 35
level with the infundibulum show an extensive acute herpetic encephalitis.
Thereisacellularexudatein themeniges abouttheinfundibulum.
Theacuteberpeticlesionissharplycircumscrbedoneach side andmoread-
vanced on the right side. Thecortical cellsof the Areapraesubicularis of the
Lobus piriformis2contain intranuclearherpetic indusionsofvarious sizesand
on the right many of these cells areundergoing necrosis and are calling out a
mononuclearcel exudate. Theareainvolvedissharplylimitedby theFissura
rhinica. On the left side the herpetic lesion has an identical distnbution, but
intranuclear bodies are less numerous and there is as yet very little necrosis.
Sections through theolfactorylobesandtractsshownolesion.
Experiment3.
R 245. Normallarge adultnon-pregnantfemale.
4/3. Placedincagewith R. 242 (Herpesrighteye,inoculated4/3).
4/4. Temp. 102.8°F.
4/5. 102.8".
4/7- I03.3°.
4/8. I110033.
4/9- 103.I .
4/10. z04.9°. Eyesdear. Nodischarge fromnose.
4/II. 103.7
4/12. 1024.
4/I4. z05.80. Eyes, nose andmouth dear. Verynervous, clonic con-
tractions ofmuscles, sick. Etheized. Pharynx, naso-pharyn=, larynx,
buccal mucosa, trachea, esophagus and stomach are smooth and pale,
showingno evidenceofinflammation. Autopsy negative.
Olfactory Lobes. Sections through the olfactory lobes and tracts show no
lesion.
Cerebrum. Sectionsthroughthecerebrumpassingthroughtheinfundibulum
shownolesion.
Pons. Sections through thepons at the entrance of the fifth nerves show a
largedestructiveherpeticlesionoccupyingthepositionofthedorsalthirdofthe
sensory divisionon therightsidecentralto theplanewhere Schwann'ssheath
islost. Thereisdestructionoffibersandmyelinsheaths, andacellularinfiltra-
tion, withmononuclearphagocytespredominating.
Medulla. Serialsectionsthroughthemedullaattheentranceoftheninthand
tenthcranialnervesshowasmallherpeticlesionineachdescendingtractofthe
fifth cranialnerve. Thereis alsoa slight cellularexudate andperivascularin-
filtration in thenudeiof theninth andtenth nerves at the floorof thefourth
ventride, butnolesioninrelationtothesenervesastheyenterthemedulla.
Ceical Cord showsnolesion.
In this case the virusentered thebrainmainly through the sensory division
of the right fifth cranialnerve, andprobably to alessextent through theleft.
Possibly virusenteredalso toacertainextent through theninthnerve.
Experiment4.
R. 246. Lirgeadult non-pregnant female.
4/3. Placedin cagewith R 244 (Herpesrighteye, inoculated4/3).
4/4. Temp. 102.80F.
36 GOODPASTURE
4/5. Temp. 102.8°.
4/7 103.I
4/8. 102.8°.
4/91103.10.
4/10. 102.70.
4/II. I03 .
4/X2. I03.80.
4/I4. ' I05.x. Eyes, ears and nose dean. No noticeable symptoms.
3 P.iwL Temp. I064°, respirations rapid. No evidenceofmuscularin-
volvement. Et Autopsynegative.
Sections through the olfactory and frontal lobes, cerebrum at the infundi-
bulum, andcervicalspinalcordshownolesions.
Ponsat enfance offiftk ne. Ontheleftsideoccupying thedorsal thirdof
thesensorydivisionofthefifthnervejustcentraltotheplanewherethesheaths
ofSchwannarelost,thereisalargeacuteherpeticlesionshowingdestructionof
fibersandmyelinsheaths, andcellularinfiltrationprindpallywithlargemono-
nuclearphagocytesfilledwithvacuoles. Thereis alsoamoderatemononuclear
cellexudateinthemeningesoverthisarea. Thereisnolesionofthemotorroot.
Fromthepointofentranceintotheponsofthefifth nerveupwardandinward
to the angle of the floor of the fourth ventricle there is a mononuclear peri-
vascularinfiltration; andinvolving theregionof theaccessory motornucleus,
the Nudeus ventralis Bracchii conjunctivi and the Bracchium conjunctivum
cerebelli there is a diffuse cellular infiltration and focal groupsoflarge mono-
nuclearphagocytes.
Ontheleftsidethereisnolesioninthesensorydivisionofthefifthnerve. In
themotornerve,however,inthebundleoffiberswhichpassesbeyondthemain
motornucleustoendintheaccessorymotornucleusattheangleofthefloorof
thefourthventricle,thereisanacuteherpeticlesionatapointjustdorsaltothe
mainmotornucleus. Heretherearenumerousneuroglia cellscontainingintra-
nuclearbodiesandaninfiltration with mononuclearphagocytes. Thereis also
a perivascular infiltration in theneighborhood ofthelesion.
Sections through the pons at the entrance of the eighth nerve show only a
lesioninthedorsalhornofthecrescenticsensorytractofthefifth nervein the
left side, a descending continuation of the lesion in the nerve at its entrance.
There isnosimila lesionontherightside.
Medula. Serial sections through the medulla show a moderate cellular in-
filtrationofthemedianportionon each sideandhereandthereafocusofleu-
cocytes. Attheentranceoftheglossopharyngealnerveintheleftsidethereisa
destructiveherpeticlesion extendinginwardalongthecourseofenteringfibers
through thesensory tract of the fifth nerve. About the entrance of the nerve
thereisacellularexudatein themeninges.
Withanarrowinterruption thelesioninvolvestheninthandtenthnuclei at
thebaseofthefourthventricle. Herethelesionislargelyinterstitialconsisting
ofadestructionoffibers, myelinsheaths andneuroglia, andacellularexudate
andperivascularinfiltration.
Asimil thoughlessextensivelesioninvolvestheentranceoftheninthnerve
ontherightside,andthecorrespondingnudeusonthisside.
In this case virus entered the pons through the sensory division of the left
fifth cranial nerve, andprobably throughthosefibersofthemotordivisionsof
thisnerveoneachsidewhichterminateinitsmesencephalicoraccessorynuclei.
PATHWAYS OF INFECTION OF THE CENTRAL NERVOUS SYSTEM 37
Inthemedulla,virusenteredthroughtheglossopharyngealnerveoneachside
producing thegreaterinjury ontheleftside.
Experiment 5.
R. 247. Normallarge adultmale.
4/3. PlacedincagewithR. 243 (Herpesright eye, inoculated4/3).
4/4. Temp. I02.90 F.
4/5. a I02.8'.
I03.2'-
4/7. a
4/8. a I03.3'.
4/9. I03°0
4/10. a aI030
4/II. a I02.4
4/I2. I02.6
4/14. a I02.4.
4/15. a 102.80.
102.40.
4/19. a Remained normal.
Experiment 6.
R. 268. Pregnant white adult female.
4/I8. Placedin cagewithR. 267 (Herpesrighteye, inoculated4/I8).
4/19. Temp. I030 F.
4/20. I03.10.
4/2I. a1030
4/22. aI030
4/23. I03*.1
4/24. I03.4.
4/25. a I03.I -
4/26. a I02.80.
4/29. a I03°. Placed in cage with R. 283 (Herpes right eye, inocu-
lated4/29).
4/30. Temp. I02.80.
s/I. a I02.80.
5/2. a 102.80.
5/3. a I02.50.
5/14. a I04.80. Aborted young almost term. Holds head backward,
weak andshaky. Emaciated.
0/I6. Dead, encephalitis. Autopsy grosslynegative.
Experiment 7.
R. 270. Young adult rabbit.
4/20. Placedincage withR. 269 (Herpes right eye, inoculated4/20).
4/22. Temp. I02.80F.
4/23. a I02.80.
4/24. a I03'.
4/25. a 102.80.
4/26. a I03.20.
4/28. a I0o6. Etherized. Eyes, ears,nose, andmouth clean. Autopsy
negative.
38 GOODPASTURE
Potsatentranceoffifth cranialxiges. Ontherightsideinvolvingthedorsal
half of the sensory division of thefifth nerve there is alargediffuse and very
acute herpetic lesion. Innumerable neuroglia cells contain herpetic inclusion-
bodiesandthereisamoderatepolymorphonudear andmononuclearleucocytic
exudateandmanysmallhemorrhages. Abouttheentranceofthenervethereis
amononuclearcellexudatein themeninges. Nolesionisobservedin thefifth
nerveontheleft, andthereisnootherlesioninthebrainatthislevel.
Sectionsoftheponsattheentranceoftheeighthcranialnervesshowanacute
herpeticlesionsimilartothatfoundintheabovesections,occupyingthedorsal
horn of the right descending tract of the sensory division of the fifth canial
nerve. Atthislevelthereisasimila lesioninthecorrespondingrightdescend-
ingsensory tract. Both theselesionsareveryacute, presentingnumerous cells
with herpetic indusions in their nuclei, and a cellular exudate in which poly-
morphonuclearleucocytesareprominent.
MeduUla. Sections through the medulla inlduding the entrace of the ninth
canialnerveshowonbothsidesanacuteherpeticlesionattheentranceofthese
nerves,andtoalesserdegreeinthecorrespondingnudeiatthefloorofthefourth
ventricle. Inthemeningesattheentrances thereisanacuteexudateofmono-
nuclearandpolymorphonuclearleucocytes. Withinthemedullarytissuealongthe
distnrbutionofthefibersofthesenerves,butmostmarkedattheperiphery,there
is an acute herpeticlesion. Innumerableneurogiacell nudeicontainherpetic
inclusionsandsimlarinclusionsarefoundinneurogliacellsintheninthnucleus
ontherightside. Inbothninthnucleithereisamoderatediffusecellularexu-
date. Nolesionsareobserved elsewhere.
In this caseherpetic virus entered thebrain through the sensory division of
the right fifth cranial nerve, and through both glossopharyngeal nerves. The
lesionseverywherearevery acute.
Experiment8.
R. 272. Adult rabbit.
4/25. Placedincagewith R. 271 (Herpes right eye, inoculated4/24).
4/26. Temp. I03°F.
4/29. £ I04
4/30. I044°
5/I1. s 104.30. Etherized. Autopsynegative.
Microscopic Notes. Sections through frontal lobes, cerebrum at infundibu-
lum, ponsandmedullashownoevidenceofherpeticinfectionofthebrain.
Thisanimaldidnothaveherpeticencephalitishistologically. Therapidonset
ofelevatedtemperatureandthefactthatthefeverremainedlowforthreedays
suggeststhatsomeothercausethananherpeticinfectionwasresponsibleforit.
Experiment 9.
R. 278. Adultpregnantfemale.
4/26. Placedincagewith R. 274 (Herpesbotheyes,inoculated4/25).
4/29. Temp. 102.5°F.
4/30. 1024°.
5/I. £ 103.9
5/2. 102.6