J. clin. Pathi. (1954), 7, 1.

ACUTE HAEMORRHAGIC LEUCO-ENCEPHALITISBY

T. CRAWFORDFroan the Department of Pathology, St. George's Hospital Medical School, London

(RECEIVED FOR PUBLICATION AUGUST 25, 1953)

It was in 1940 that Weston Hurst (1941) encoun-tered two cases of fatal encephalitis which heregarded on clinical and pathological grounds asrepresenting a previously unidentified entity towhich he gave the name of acute haemorrhagicleuco-encephalitis. To quote Hurst's originaldescription, the disease was "an acute 'cerebralcondition, virtually localized as far as the cerebrumwas concerned to the white matter, and developingmore or less abruptly in apparently normalindividuals. Perivascular necroses, perivascularand focal demyelination, haemorrhages, oedema,and cellular infiltration were the chief componentsof the pathological picture."

In the 12 years since Hurst's paper appearedremarkably few similar cases have been reported,and in fact only five further examples have beendescribed under the same name. These have beenrecorded by Henson and Russell (1942), Shallardand Latham (1945), MacArdle, van Bogaert, andLhermitte (1949, two cases) and by Greenfield(1950). It so happens that three characteristicexamples of the disease have occurred in theneurosurgical department of St. George's Hospitalover a two-year period, and it seems probable thatthe condition is not such an extreme rarity as thesmall number of recorded cases would indicate.The object of the present communication is to puton record these three further cases (bringing thenumber recorded up to 10) and to draw the atten-tion of general pathologists to the existence of thisvariety of encephalitis. The descriptions of thedisease which follow are based on the three newcases together with the seven previously reported.More detailed summaries of the three cases areincluded in an appendix to this paper.

Clinical FeaturesThe salient clinical features are summarized in

Table I. The age of the patients has varied from2 years 10 months (Case 2 of the present series) to51 years (Greenfield, 1950), but seven of the 10patients were young adults in the third and fourth

A

decades. The sex incidence shows a male prepon-derance with seven male and three female patients.The duration of the disease has proved variable.In seven cases the onset of neurological signs was

TABLE ISUMMARY OF CLINICAL COURSE

Duration (Days)

Author Age Sex Pro- Inter- Neuro-(yrs.) dromal Inalr logicalStage vlStage

Hurst (1941):Case 1 33 F Right flaccid 0 0 2

paralysis,speech loss,coma

2 33 M Sore throat, fever, 10 11 6speech loss,,fit, coma

Henson and 21 M Cold, right hemi- 3 8 5Russell paresis, decere-(1942) brate rigidity

Shallard and 7 F Cold, right hemi- 2 0 4Latham paresis, coma,(1945) flaccidity

MacArdle etal. (1949):Case I 22 M Fits, coma, right 0 0 4

hemiplegia2 37 F Confusion, speech 0 0 5

loss, right-sidedfits, coma

Greenfield 51 M Bronchitis, drow- ?15 0 4(1950) siness, right-

sided fits, coma

Presentauthor:

Case I 28 M Cold, vomiting, 4 8 4coma, ventri-cular shift toright

2 .. 210/12 Laryngitis, vomit- 3 0 5ing, fits, lefthemiplegia,coma

3 .. 31 M Bronchitis, drow- 2 3 5siness, coma

preceded by a prodromal period of upper respir-atory infection lasting from as little as two daysup to about 15 days, and in four cases theprodromal infection was separated from theencephalitic stage by a few days of apparentrecovery. The longest survival after the onset of

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T. CRAWFORD

neurological signs was six days, while Hurst'soriginal patient died after only 42 hours' illness.A detailed account of the symptoms and signs

is beyond the scope of this paper. Striking features,however, are the early onset of coma and the fre-quent gross asymmetry of the signs. This asym-metry has been conspicuous in nine of the 10 casesand has sometimes led to needling of the brain insearch of an abscess or other focal lesion. Sixcases have shown right hemiparesis with earlyspeech involvement.

Clinical PathologyIt is unfortunate that few laboratory tests have

been recorded on material obtained from thesepatients during life-a fact no doubt associatedwith the rapid downhill course of most cases. Suchinformation as is available is summarized in TableII. In the cerebrospina) fluid the cell count varied

TABLE 11CLINICO-PATHOLOGICAL FINDINGS

Cerebrospinal Fluid Blood

Author Cells Poly- Protein White Poly- Urine(per morphs (mg. (pcerls morphs

c.mm.) ()100, Ml. (per.)Hurst (1941):

Case I - -

,,2.. -_ - 22,900 -_

Henson and 0 - 40 12,000 82 AlbuminRussell +(1942) 6 33 35 - - Casts + t-

Shallard and 200 90 30 - -

Latham(1945)

MacArdle etal. (1949):Case ..I - - - _

to 2 6 - 55 - - Albumin

Greenfield 342 84 60 - -__(1950)

Presentauthor:

Case 1 220 84 80 - - No protein2.. 2 - 30 30,000 81

",3.. 150 71 140 - _

from normal up to a count of 341 per c.mm. andthe elevated counts were always associated withconsiderable numbers of polymorphonuclearleucocytes, the proportion of these cells alwaysexceeding 70% with total counts over 100 perc.mm. The cerebrospinal fluid protein level wasalso moderately elevated in most cases, the highestlevel noted being 140 mg. per 100 ml. (presentseries, Case 3). The cell and protein increaseswere approximately proportionate except for thecase of Shallard and Latham (1945) in which thecerebrospinal fluid showed a cell count of 200 per

c.mm. (90% polymorphs) but a protein level ofonly 30 mg. per 100 ml. Three observations ofthe cerebrospinal fluid sugar and chloride levelsfall within normal limits. Blood counts were

recorded in only three cases, two showing a highand the third a moderate leucocytosis, while twodifferential counts both revealed polymorpho-nuclear increase. Examination of the urine was

not recorded in five of the cases. Of the others, one

showed heavy albuminuria with casts (Henson andRussell, 1942) and one slight albuminuria (Mac-Ardle et al., 1949, Case 2). In the three cases of thepresent series protein was absent from the urineat a single examination in each.

The Naked-eye LesionsThe meninges have usually shown no naked-eye

change, but sometimes they appear congested(Henson and Russell, 1942; present series Cases1 and 3). Greenfield (1950) noted some creamyexudate over the convexity of the left frontal lobe.The most characteristic lesion is seen in the whitematter of the cerebral hemispheres and takes theform of haemorrhages varying in size from minutepoints up to areas a few millimetres in diameter,which, in the more severely involved regions, maybecome confluent (Fig. 1). These more affectedparts show asymmetrical oedematous swelling with

..,1J... t _. 4X 5 6 7 8. 9 10 1 1L2i3 1415 16FIG. I.-Three pieces of the left cerebral hemisphere from Case 1.

Petechial haemorrhages, in places confluent, are scatteredthroughout the white matter and there is haemorrhage in thetrack of an exploratory needle.

L21 3LL4 51L6L 8iL9 1O IFIG. 2.-Cerebellum and brain-stem from Case 3. There are numerous

petechial haemorrhages in the white matter.

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g;~ ~~,,,*a,wsQ^

'V AA*1C

FIG. 3.-Ball and ring haemorrhages in the 4L.t &;Vparietal white matter (Cas 1) Phoie

FIG. 4.-Disrupted capillary in the centre of a X z <s Z Fball haemorrhage (Case 1). Picro-Mallory r$

FIG, 5.-Leucocytic exudate, chiefly polymor-phonuclear, in the sheath of a small vein -..

(Casec2). Haematoxylin and eosin x 180. ALtfi *

X ~~'t 'w-z>'i.--0-.

<irNb. S

'a. *. - b * *, b; ¢ o- ..

FIo. 5

FIG. 4

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FIG. 8

FIG. 6

FIG. 6.-Fibrin impregnation of the walls ofvenules in the white matter (Case 2). Acid-picro-Mallory x 175.

FIG. 7.-Fibrin impregnation extending throughthe vessel wall into the adjacent whitematter (Case 1). Acid-picro-Mallory x 312.

FIG. 8.-Fibrin deposit around the lining of avenule and extending through the wail tothe perivascular sheath (Case 1). Acid-picro-Mallory x 312.

FIG. 9.-Fibria-plugged capillaries in the whitematter (Case 2). Acid-picro-Mallory x 130.

FIG. 10.-Multiple foci of demyelination in thecerebellar white matter (Case 3). Loyezx 35.

FIG. 1 .-Demyelination in an area of haemor-rhage (Case 3). Loyez x 100.

FIG. 12.-Perivascular demyelination (Case 3).Loyez x 120.

FiG. 7

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4~~~~~~~~~4

6' 4*-*., .* --0.

FIG...

--5:i- ; S

* A^ S . * *1

*~~~~~~~FG p

FIG. 10

FIG. 11 Fio. 12

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T. CRAWFORD

pinkish or grey discoloration and the most severelyhit area may be of an almost gelatinous consis-tency.The distribution of these lesions is highly

characteristic and is summarized in Table II1. Thehaemorrhages involve the white matter only, thegrey matter showing nothing more than somevascular engorgement. The central white matterof one or both cerebral hemispheres is regularlyinvolved and in most cases has shown the mostsevere lesions. The haemorrhages may extendinto the white cores of the convolutions, but theU-fibres between adjacent convolutions are usually

TABLE IIIDISTRIBUTION OF NAKED-EYE AND MICROSCOPICAL

LESIONS

Author

Hurst (1941):Case I

, 2

Henson andRussell (1942)

Shallard andLatham (1945)

MacArdle et al.(1949):

Case 1

,, 2

Greenfield (1950)

Present author:Case 1

,, 2 .

, 3 ..

Areas Affected

Left centrum semi-ovale, corpus callosum,cerebellar peduncles, pons, cerebellum*

Left centrum semi-ovale, corpus callosum, rightcentrum semi-ovale,* mid-brain,* pons*

Central third of white matter of both cerebralhemispheres, corpus callosum,* pons*

Central white matter of left cerebral hemisphere.cerebellum*

Central white matter of both hemispheres,cerebral peduncles, pons, cerebellum*

Central white matter of both hemispheres, leftmore affected than right

Central white matter of both hemispheres.corpus callosum, pons*

White matter of both hemispheres, mid-brain,pons

Left temporal white matter, central white matterof both hemispheres

Central white matter of both hemispheres, mid-brain, cerebral peduncles, cerebellum, pons

* These regions showed microscopical lesions only.

spared. The corpus callosum has shown naked-eye lesions in half the cases. The level to whichthe lesions descend has varied greatly in the 10cases. They have been noted in the cerebralpeduncles in three cases and in the pons in four,but Case 3 of the present series is the first in whichthey are recorded in the white matter of thecerebellar hemispheres (Fig. 2), though other cases

have shown microscopic lesions there.

HistopathologyThe distribution of the microscopic lesions

(Table III) is more widespread than of the naked-eye lesions, but the former, like the latter, are

virtually limited to the white matter. They extendover a wider area of the hemispheres and to a

lower level in the brain stem, the cerebellum beingquite frequently involved (three cases). It is con-venient for descriptive purposes to consider the

different types of microscopic lesion separately.but it must be emphasized that a combination oflesions may occur at a single site: for example.haemorrhage, demyelination. and n.urofibril dis-integration.

Haemorrhage. The haemorrhages are themost conspicuous lesion in ordinary preparations.Their structure is best studied in less severelvaffected areas where they are small and discrete.Two types are described : ball haemorrhages andring haemorrhages (Fig. 3). The ball haemorrhageis a minute sphere of extravasated blood, andserial sectioning will usually reveal a disruptedcapillary in its centre (Fig. 4), but the ring haemor-rhage has a non-haemorrhagic centre in which itis often possible to find a capillary plugged withfibrin. Owing to the rapidly fatal course of thedisease the extravasated red corpuscles appearintact in sections and have not lost their haemo-globin.Two types of exudate may also be distinguished.

cellular exudate and serous exudate. A moderatecollection of leucocytes may be seen in the pern-vascular space around many of the small venulesin an affected part (Fig. 5). In transverse sectionthe cells often form an asymmetrical buLlge, break-ing out from the vessel sheath and spreading intothe adjacent brain tissue. A high proportion ofthe cells are neutrophil polymorphonuclear leLuco-cytes. There is a varying admixture of lympho-cytes and histioeytes, but plasma cells and eosino-phils have not been noted.The appearance referred to as " serous exudate

is a rather striking finding seen in all three casesof the present series and well illustrated by Hensonand Russell (1942). It consists of homogeneous.indifferently staining material distending the pern-vascular sheath and in places bursting oLIt into theadjacent white matter. Sometimes there is con-siderable contamination with red blood corpuscles.

Lesions in Blood Vessels.-The lesions in theblood vessels constitute what are perhaps the mostcharacteristic microscopic features of the disease.The small venules of the white matter are thevessels most affected but there are lesions also inthe capillaries and sometimes in small arterioles.The most characteristic lesion is shown in Fig. 6.It consists of impregnation or replacement of thetissues forming the vessel wall with material givingthe staining reactions of fibrin, while similarmaterial is present in varying amounts in theperivascular space. A modification of this lesionis depicted in Fig. 7 in which the fibrinimpregnation extends beyond the vessel wall and

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ACUTE HAEMORRHAGIC LEUCO-ENCEPHALITIS

perivascular space far into the surrounding whitematter. Sometimes the fibrin-impregnated tissueforms a halo outside an intact vessel wall andsheath, while another appearance (Fig. 8) is ofa plastering of fibrin around the inside of thevessel wall often extending through the thin wallto the perivascular sheath. Endothelium maygrow over the deposit to line the new narrowedlumen, and the whole appearance is then remin-iscent of the description given by Duguid andAnderson (1952) of hyaline sclerosis in the splenicarterioles.

Capillary disruption and obstruction in associa-tion with the haemorrhages have already beenmentioned. Groups of fibrin-plugged capillariesmay also be found without'any apparent relation-ship to haemorrhages (Fig. 9).The application of myelin stains to this material

reveals the presence of widespread foci ofdemyelination (Fig. 10). Closer inspection showstwo types of demyelinated area-irregular patchesin and around the areas of haemorrhage (Fig. 11)and narrow zones around small blood vessels (Fig.12). Cells are scanty in the demyelinated areas.Appropriate staining methods show disruption ofthe neurofibrils in relation to many of the foci ofdemyelination. Microglial proliferation occurs inthe affected areas and in the cases of longer stand-ing fat phagocytes collect around the degeneratefoci.

Cellular degeneration affecting pyramidal andPurkinje cells, astrocytes, oligodendroglial cells,ependymal cells, and cells of the choroid plexuswas noted by Henson and Russell (1942), buthas not usually been conspicuous.

DiscussionThe addition of these three further cases to the

small group of cases already published strengthensHurst's contention that acute haemorrhagic leuco-encephalitis is a specific disease entity distinctfrom other forms of encephalitis. The specificpathological features which justify the classifica-tion of a case into this type of encephalitis aremultiple capillary haemorrhages, focal and peri-vascular demyelination, and the characteristicfibrin impregnation of the vessel walls, with apredominantly polymorphonuclear exudate allvirtually limited in their incidence to the whitematter.

Search of the literature shows few cases otherthan the seven already considered which fulfilthese conditions. Adams, Cammermeyer, andDenny-Brown (1949), however, described underthe name of "acute necrotising haemorrhagic

encephalopathy" four cases which, though differ-ing from the accepted cases in detail, did showthese main points. Two of the cases occurred inthe United States of America and two in Norway.There were three male patients (aged 33, 34, and46 years) and one female patient (aged 56 years).All showed a prodromal period of upper respir-atory infection and all died within 30 to 60 hoursof the onset of neurological features. The maindifferences from the 10 cases discussed above arein the cerebrospinal fluid findings and in the dis-tribution of lesions. The two cases in whichcerebrospinal fluid cell counts are recorded showedcounts reaching 5,000 and 1,600 per c.mm. with100% and 85% polymorphs. Some ratherequivocal findings of pyogenic cocci in the tissuesof the former leave doubts as to its true nature.In addition in two of the cases the white matterof the cerebral hemispheres was spared and lesionsoccurred only in and below the mid-brain.As regards the differential diagnosis, acute

haemorrhagic leuco-encephalitis has to be distin-guished from other causes of multiple petechialhaemorrhages and other causes of multiple fociof demyelination. Once microscopic sections areavailable the combination of haemorrhages,demyelination, and fibrin impregnation in andaround the vessel walls leaves little doubt of thenature of the disease. The closest mimicry of thenaked-eye lesions is sometimes seen in cerebral fatembolism in which haemorrhages may be limitedto the white matter. Other forms of brain purpurausually involve grey and white matter alike.The aetiology of the disease and the pathogenesis

of the lesions form an interesting speculation. Themain aetiological possibilities to be considered are(1) invasion of the brain tissue by bacteria or virus,(2) direct action of circulating toxins on the braintissue, and (3) acquired sensitivity of the braintissue to. a circulating antigen. Bacteria have notbeen demonstrated in any of these cases andsearch for a virus has not been reported. InCase 3, however, of the present series some cerebraltissue was obtained immediately after death andtwo injections of this material were given into thethalamic areas of a rhesus monkey. The monkeyshowed no abnormal signs apart from slightpyrexia for two days. It was killed 31 days afterthe first injection but the brain and cord showed noevidence of disease. Passage was not carried out.In addition the structural lesions (particularly thevascular disruption and the polymorphonuclearexudate) and the distribution of the lesions areunlike the findings in any known virus disease.The possibility of direct toxic action is supported

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by Hurst's observation (1940) that chronic cyanidepoisoning in monkeys could lead to focal demye-lination, but in none of the cases of acutehaemorrhagic leuco-encephalitis has there beenevidence of any direct toxic action of this kind.The third possibility acquired sensitivity to acirculating antigen has certain points in itsfavour. The frequent onset of the brain lesionssome days after a respiratory infection is in keep-ing with the time interval observed with otherhypersensitivity states. In particular the lesionsare similar to those seen in arsphenamine enceph-alitis. Russell (1937) described three cases of thiscondition and drew attention to the evidencesuggesting that it was a sensitization phenomenon.More recently Cavanagh (1953) has describedsomewhat similar lesions in a patient who diedwith evidence of hypersensitivity following admin-istration of streptoniycin and para-amino-salicylicacid. Furthermore the vascular lesion resemblesclosely that occurring in polyarteritis nodosa andproducible experimentally in animals by therepeated injection of foreign protein (Klinge.1929), while the demyelination can be imitatedexperimentally in animals by multiple injections ofemulsions of brain tissue, with or without certainadjuvants (Rivers, Sprunt, and Berry, 1933: Riversand Schwentker, 1935; Kabat, Wolf, and Bezer,1947; Lumsden, 1949). The dangers inherent inassuming that similar histological lesions are ofsimilar pathogenesis are well known: neverthelessthis similarity of the lesions in the human diseaseto experimental hypersensitivity lesions and tolesions occurring in drug sensitization is the onlypositive guide to aetiology in this instance. Clearly,more information is needed on many aspects ofthe problem, but at present such evidence as thereis suggests that the lesions result from hyper-sensitivity of the brain tissue to a circulatingantigen acquired during some upper respiratoryinfection.

SummaryThree new cases of acute haemorrhagic leuco-

encephalitis are described, bringing the total ofrecorded cases up to 10. The disease occurs pre-dominantly in young adult males.The encephalitic stage, which is rapidly fatal, is

often preceded by a prodromal period of upperrespiratory infection.

Polymorphonuclear leucocytosis in the bloodand cerebrospinal fluid is the most striking featureof the clinical pathology. The brain lesions arelimited to the white matter and are often maximalin the centrum ovale of the hemispheres. They

take the form of capillary haemorrhages, poly-morphonuclear and serous exudate, fibrin impreg-nation of vessel walls, capillary plugging, focaldemyelination, and microglial proliferation.The nature of the lesion is uncertain. Search

for a causative virus in material from one case wasnegative. 'There is some evidence that the lesionsmay be associated with acquired sensitivity of thebrain tissue to a circulating antigen.

I wish to thank Mr. Wylie McKissock, neurosurgeonto St. George's Hospital, for permission to make useof his case records, and Dr. F. 0. MacCallum of theCentral Public Health Laboratory for carrying out theanimal inoculations with materiai from Case 3.

APPENDIX

Summaries of Case Histories and Post-mortemFindings

Case I. A man. aged 28 years. a radio-operator(aircraft). 12 days before admission to hospital devel-oped a feverish cold which lasted four days. Hereturned to work but six days later became suddenlyseverely ill with vomiting, headache, and fever. Oiladmission two days later he was semi-conscious,aphasic. and incontinent. Neurological examinationshowed a small haemorrhage in the right fundus, equalbut sluggishly reacting pupils, and right upper motorneuron facial weakness. The tendon reflexes wereincreased on the right side and the plantar responsewas extensor on the right. flexor on the left. A radio-graph of the skull showed a slight pineal shift to theright. A left temporal-lobe abscess was suspected butexploration proved negative. Ventriculography showeddepression of the body and anterior horn of the leftlateral ventricle. Cerebrospinal fluid obtained fromthe right lateral ventricle was under increased pressureand gave a white cell count of 220 per c.mm. (poly-morphs 84°o) and protein level of 80 mg. per 100 ml.He gradually became more deeply comatose and diedfour days from the onset of neurological signs.At post-mortem examination there was evidence of

acute bronchitis but otherwise the findings were limi-ted to the brain and are summarized in Table 111.Microscopic examination showed widespread haemor-rhagic, exudative. and demyelinating lesions of thetypes described in the text above. Fibrin infiltrationin and around the vessel walls was a conspicuousfeature.Case 2.-A boy, aged 2 years 10 months. was healthy

until July 19, 1952, when he developed cough andhoarseness. Two days later he became restless andflushed and vomited repeatedly. That evening hedeveloped left-sided convulsions and was admitted tohospital. The temperature was 104.6° F. and he hada left hemiplegia and injected tonsils. A white bloodcount gave 30,000 per c.mm. (polymorphs 810,'). Theears were normal. He was given penicillin and his

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temperature fell to normal, but coma and hemiplegiapersisted and he was transferred to the neurosurgicalcentre on July 24 as a possible case of brain abscess.Neurological examination there showed response topainful stimuli only. There was moderate neck rigid-ity but Kemig's sign was negative. The eyes deviatedto the left and upwards, the left pupil larger than theright, the right pupil only reacting to light; the fundiwere normal. Other cranial nerve functions werenormal. There was paralysis of the left arm and legwith increased tone ; abdominal reflexes were presentbut reduced on the left; the right plantar responsewas flexor, the left extensor. The cerebrospinal fluidat first (July 21) showed no abnormality and was notre-examined. Ventriculography (July 24) showed somedisplacement of the ventricles to the left but needlingthe right hemisphere did not reveal an abscess. Thedepth of coma increased and he died on July 27.Post-mortem examination revealed extensive pul-

monary oedema with patchy bronchopneumonic con-solidation. The brain showed bulging of the righttemporal region and on sectioning there was ill-defined,pinkish-grey discoloration of the white matter in thisarea. Close inspection showed many minute haemor-rhagic points in the white matter of both hemispheres.Microscopic examination of the discoloured areashowed haemorrhages varying from minute groups ofred cells up to areas about 3 mm. in diameter. Manyof the haemorrhages had a perivascular distribution,and many of the venules and arterioles showed fibrinimpregnation of their walls. Cellular exudate wasscanty, but here and there the vessels were surroundedby cuffs of polymorphs and mononuclear cells. Ex-tensive demyelination was present in the discolouredarea and many smaller foci of demyelination occurredin adjacent areas of white matter and in the rightcentrum semi-ovale. The mid-brain, brain-stem, andcerebellum were not involved.

Case 3.-A man, aged 31 years, was employed as acost accountant. On December 24, 1952, he developeda severe cough and vomited twice. The cough con-tinued and on December 27 he had severe frontalheadache with further vomiting. Two days later he

drowsy and later unable to recognize his family.Following admission to a local hospital where lumbarpuncture was performed (cerebrospinal fluid reportedas "cloudy, protein 270 mg. per 100 ml.") he wastransferred to the neurosurgical centre as a case ofbrain abscess on December 31. He was then deeplycomatose, and examination of the nervous systemgave the following positive findings: extensor spasmsof upper limbs on painful stimulation; considerableneck rigidity; pupils contracted and unreactive; limbsextended and spastic but reflexes present and equal;abdominal reflexes absent; right plantar responseflexor, left extensor. There was no evidence of otitis,and other systems proved normal. Ventriculographyshowed a normal ventricular system and the ventri-cular cerebrospinal fluid contained 150 cells per c.mm.(polymorphs 70%) and 140 mg. protein per 100 ml.His temperature fluctuated from 990 F. to 101.6° F.In the early part of his illness he was treated withpenicillin and later with streptomycin, but he neverregained consciousness and he died on January 3,1953, at 11 a.m., five days after the onset of signs ofinvolvement of the nervous system.At post-mortem examination there was extensive

bronchitis and bronchiolitis with patchy broncho-pneumonic consolidation of the lower lobes of thelungs. Other positive findings were limited to thebrain and are summarized in Table III. Microscopicexamination of the brain showed all the types oflesion described above.

REFERENCESAdams, R. D., Cammermeyer, J., and Denny-Brown, D. (1.949).

J. Neuropath., 8, 1.Cavanagh, J. B. (1953). Journal of Clinical Pathology, 6, 128.Duguid, J. B., and Anderson, G. S. (1952). J. Path. Bact., 64, 519.Greenfield, J. G. (1950). Brain, 73, 141.Henson, R. A., and Russell, D. S. (1942). J. Path. Bact., 54, 227.Hurst, E. W. (1940). Aust. J. exp. Biol. med. Sci., 18, 201.- (1941). Med. J. Aust., 2, 1.Kabat, E. A., Wolf, A., and Bezer, A. E. (1947). J. exp. Med., 85,

117.Klinge, F. (1929). Beitr. path. Anat., 83, 185.Lumsden, C. E. (1949). Brain, 72, 198.MacArdle, J.. Bogaert, L. van, and Lhermitte, F. (1949). Rev.

neurol., Paris, 81, 709.Rivers, T. M., and Schwentker, F. F. (1935). J. exp. Med., 61, 689.- Sprunt, D. H., and Berry, G. (1933). Ibid., 58, 39.Russell. D. S. (1937). J. Path. Bact., 45, 357.

atham, 0. (1945). Med. J. Aust., 1, 145.

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