VISCERAL LESIONS IN POLIOMYELIJIS *

Orro Sam- MD.(From the Departmeut of Pathology of th Michad Reese Hospital, Chao, Ml.)

While poliomyelitis is the subject of much research, and many stud-ies on its etiology, its epidemiology, and its immunologc and serologicaspects are on record, recent gross and histologic studie of organsother than the brain and spinal cord are singLularly lacking. An excep-don is the recent report of Dublin and Iarson 1 upon the results of12 post-mortem e ations made during the epidemic of 1940 iPierce County, Washington. They found, in addition to the lesIonsin the brain and spinal cord, lymphoid hyperplasia of the intestinamucosa and mesenteric nodes, acute myocarditis twice, and broncho-pneumonia in three instances, with abscess formation in one. Appar-ently one of these instances of myocarditis had been previouslyreported by Larson2 (1941). Hemorrhagic pulmonary edema wasoutstanding in three cases. The liver regularly disclosed some degreeof hydropic change and, in some instances, fatty degeneration.

This study is based on post-mortem exmnations of 17 patients whodied of clinially diagnosed poliomyelitis during the recent Chicagoepidemic. The duration of the disease varied from 3 to 8 days. Thediagnosis of bulbar and spinal poliomyelitis was made in I3 cases.Bulbar poliomyelitis was diagnosed four times, and in one of theseencephalitis was also recognized clinically. There were 12 childrenunder 14 years of age, 2 adolescents, I6 and 17 years old, and 3 adults,20, 23 and 28 years old. All patients had received various amounts ofeither convalescent humnan serum or pooled normal human serum. Sixpatients received sulfadiazine. A respirator was used for 4 patients.The outstanding changes encountered at autopsy were as follows:

The hearts were dilated and often soft and flabby. The mural andvalvular endocardium was smooth. The papilary muscles and chordaetendineae were flattened. The myocardium invariably was pinlkishgray or brownish gray and of boiled appearance with loss of its normalarchitecture. Petechial hemorrhages were often encountered in theendocardium and epicardium- In one instance they were abundant andcovered practically the entire visceral pericardium.The lungs grossly dislosed several findings. In ten instances marked

edema and acute hyperemia were encountered. Slight bronchopneu-monia was detected three times and severe bronchopneumonia twice. In

* his study ws aided by a grant from the Otto Baer Fund. Research in this de-partment is in part supported by the Miae Reese Reh Foundation.

Received for publication, April x, I944.

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six lungs in which either edema and hyperemia or no gross changewas encountered, significant lesions were discovered on microscopicexamination. The bronchi and trachea showed no lesion in theseinstances. In some of these latter patients, attending physicians haddiagnosed a mucous plug in the bronchus. It was surprising that sucha mucous plug was actually encountered at necropsy only once. Mod-erate emphysema was found twice in children who, because of difficultyin breathing, had been placed in a Drinker respirator. Edema andhyperemia also were found in these lungs. Only the lungs of i patientwere free from pathologic change.

Cloudy swelling of varying degree was invariably present in theliver and in the kidneys. In the latter, however, passive hyperemiawas the outstanding finding.The intestinal tract disclosed most commonly a marked hyperplasia

of the lymph follicles and of Peyer's patches. There was also, in theseinstances, a hyperplasia of the peritoneal lymph nodes. Occasionally,hyperplasia of the Peyer's patches was so severe as to resemble thatseen in the stage of medullary swelling of typhoid fever. It may benoteworthy, however, that the hyperplasia was not observed in 3patients, the oldest in this series, who were 20, 23 and 28 years old,respectively.

Cerebrospinal lesions may be summarized only. Twelve patients dis-closed inflammatory lesions in the brain itself in addition to thelesions in the medulla oblongata and spinal cord. The regions sur-rounding the ventricles were most commonly involved. These changeswere particularly common in the vicinity of the fourth ventricle. Thecerebellum was also frequently involved. The most outstandinig sitewas the dentate nucleus. The spinal cord disclosed grossly recogniza-ble, minute and larger foci of hemorrhage within the gray matter.These lesions were encountered always, but not exclusively, in itsanterior horn. Often the posterior portions were also involved butusually to a lesser degree. The changes were marked in the cervicaland often in the upper thoracic cord, and became less pronounced orwere absent in the lower thoracic segment, but again were more promi-nent in the lumbar region.

Microscopic examination of the myocardium disclosed myocarditisin ten instances. In two the inflammatory changes were very markedand diffuse, in six they were more or less localized, and in two heartsthe changes were only slight. In the first two hearts the changes wereso severe that there seemed to be a massive extravasation of leukocytes.Many polymorphonuclear leukocytes were encountered and alsolymphocytes. The proportions of these two cell types varied markedly

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VISCERAL LESIONS IN POLIOMYELITIS

in the various sections. Red blood corpuscles also were present in theinflammatory exudate. Many heart muscle fibers were compressed bythe exudate and appeared thinned out, while others were the seat ofcloudy swelling. There was no evidence of necrosis. In the six in-stances in which the nflammatry exudate was lized, it was seem-ingly confined to the interstitial tissue. This exudate consisted oflymphocytes and only a few polymorphonuclear leukocytes. Endothe-lial leukocytes were rarely encountered. Both the right and left ven-tricles were involved. Often the inflammatory change were mostmarked in the vicnity of epicardial hemorrhages.The aortas, which grosly had disclosed no noteworthy canges, were

the seat of microscopic alterations in three instances. There was anedema-like material seen in the media separating the elastic l aeand sometims nterrupting their course. Often this material had apinkish, smudgy, fibrinoid apearance. Here and there an occasionallymphocyte could be made out. Neither the intima nor adventitiashowed any chane.

In the lungs, the lesions encountered grossly could easily be verifiedmicroscopicaly. Thus, edema and hyperemia were very often seen,and bronchopneumomain varying degrees was observed five times; inthree it was very slight. However, in six additional instances definiteinterstitial pneumonia could be demonstrated It was noted that thesmaller bronchi in these instances disclosed the presence of lympho-cytes and of polymorphonucleai leukocytes within the submucosa,whereas the lining cells of the mucosa were intact. The lumina of thesebronchi did not contain an appreciable number of inflammatory cells.The only noteworthy chage in the mucosa was a thickening of thebasal membrane. It could be demonstrated that the inflammatory cellsfrom the submucosa of the smaler bronchi extended either within oralong minute vessels into the alveolar septa, which often were crowdedwith lymphocytes, polymorphonuclear leukocytes and red blood cor-puscles. Here and there some of these inflammatory cells extendedinto the adjacent alveoli. Occasionally a thin eosinophilic, homogen-eous material could be made out lining the inner wall of the neighbor-ing alveoli. The larger bronchi and the trachea also had a thickenedbasal membrane of the mucosa and, sometimes, varymg numbers ofinflammatory cells throughout their walls. The lumina rarely containedan accumulation of mucus. As stated before, a mucous plug was en-countered grossly only once. The lining epithelial cells of the tracheaand larger and smaller bronchi were carefully examined for inclusionbodies. In not a single instance, however, were inclusion bodies en-countered.

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SAPHIR

The solitary follicles and Peyer's patches in the lower ileum andcecum were sometimes enormously hyperplastic. The hyperplasiainvolved the germinal centers. There was, however, no evidence ofnecrosis in these areas. The adjacent regions of the intestinal tractshowed no inflammatory changes whatsoever. The spleen and mesen-teric lymph nodes also disclosed follicular hyperplasia with conspicuousgerminal centers. In the midst of some of the latter, foci of necrosiswere discernible. No other change could be detected. In the remainingviscera there were no noteworthy histologic lesions.The microscopic changes in the brain and spinal cord will be enumer-

ated only, since there are many reports on record describing thesechanges and this study contributes no new details. As noted grossly,the more severe lesions in the cerebrum and cerebellum were foundin the vicinity of the ventricles, particularly about the fourth ventricle.The dentate nucleus was frequently involved. Many ganglion cellsdisclosed degenerative changes with absent nuclei and with Nissl'sgranules obscured. Lymphocytes and occasionally-in some instances,however, more pronounced-polymorphonuclear leukocytes were en-countered perivascularly. Here and there small accumulations of pro-liferated microglial nuclei could be seen. In the spinal cord the changesin general were not confined to the anterior portions of the gray mat-ter, though they were most conspicuous in these areas. The changesconsisted of marked hyperemia, minute foci of extravasation of redblood corpuscles, and perivascular infiltrations of lymphocytes, mainly,and a few polymorphonuclear leukocytes. Hemorrhage never consti-tuted a predominating feature. In the more severe examples the in-flammatory cells were found diffusely throughout the gray matter.Here and there ganglion cells, evidently necrotic, were found in themidst of the inflammatory exudate. Endothelial leukocytes, thoughin general not numerous, seemed to be relatively more frequent in theseareas. Often the regions surrounding the central canal were the seatof an inflammatory reaction. Although the white matter of the cordwas rarely involved, small infiltrations of lymphocytes occasionallywere observed. The meninges also contained inflammatory cells moreor less confined to the perivascular areas, particularly in the moresevere instances.

COMMENTAside from the known lesions in the brain and spinal cord, the more

outstanding changes encountered in these I7 cases of poliomyelitiswere myocarditis and interstitial pneumonia.

Myocarditis was found ten times. It must be stressed that in someinstances myocarditis was recognized in the first few sections exam-

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ined, but in the majority a number of blocks had to be mied beforeevidence of myocarditis was found. From this study it seems evident,and it apparently also holds true for many other infectious dissesthat myocarditis will be encountered frequently if the m isexamined histologically with the specific purpose of either ruling outor establig the presence of inflammatory alterations.

Since myocarditis is known to occur in stans of pneumonia 3 oras a result of sulfa drug m tion,4 the quetion arises as to whetheror not the myocarditis in poliomyeUits may be related to these twofactors. However, the <linical records disdosed that 4 of the Io patientsdid not receive sulfa dru, though the remainig 6 did receive sulfa-diazine. Only 4 of the patients showed at necropsy evidence of pneu-monia AUl patients were treated clinically with either pooled serum orserum taken from patients who had recovered from p mis. Itdoes not seem likely that the myocarditis signifies a so-called serumreaction, since an exudative reaction following amintion of ho-mologous human serum is allegedly very rae.5 None of the patientsshowed any clinical signs or symptoms which possibly could be theresult of an abnormal serum reaction. It should be pointed out thatthe patient who had the most severe myocarditis had received poolednormal serum and not convalescent serum. In this series there was norelationship betwreen the presence or Of and thetype of poiomyelitis, whether bulbar or spinal.An instance of polioencephalomyelitisa with optic neuritis

and myocarditis was reported as early as 1913 by Hertz, Johnson andDepree.' However, this was a cinica observation, and no autopsy wasperformed to verify the clinicl diagnos of myocarditis. Wile and I srecorded myocarditis in poliomyelitis in six of seven hearts which werespecif ly examined histologically for myocarditis. Peale and Luc-chesi 8 found myoditis of some degree on histologic mit inseven of nine hearts of patients with poliomyelitis. Larson2 statedthat since neither bronheumoia nor any other source of infectionwas found in his patient as the cause of the myocarditis, it may betheorized that the myocardial involvement was produced by the virusof poliomyelitis.The sudden death of some of these chidren can easily be explaied

by the myocarditis. Hassin 9 described a child with poliomyelitis, whopresented a clinical picture of Landrys paralysis with microscopicinflammatory changes within the muscles. The sudden death of thischild was attributed to involvement of the myocardium.

Another interesting fining in this series was the presence of aninterstitial pneumonia. It was observed that the inflammatory exudate

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spread from the submucosa of the smaller bronchi into the peribron-chial tissues and thence into the alveolar septa. The inflammatory cellswere lymphocytes and polymorphonuclear leukocytes, sometimes theformer being more numerous. This interstitial involvement of the lungwas often found in conjunction with a severe hyperemia. It is note-worthy that this type of pneumonia was encountered in those in-stances in which there was much cyanosis clinically, and when theattending physician had expected a mucous plug within the tracheaor bronchi. This pneumonia resembled so-called atypical pneumonia.However, the inflammatory cells were not principally monocytes as inatypical pneumonia. Though no inclusion bodies were found anywherein the lungs, it is possible that a virus may have caused this pneumonia.It might be of interest in future cases to conduct virus studies withmaterial taken from the lungs of patients who die from poliomyelitis.

Hyperplasia of the intestinal lymph follicles and Peyer's patches hasoften been observed and originally suggested the gastrointestinal tractas the portal of entry.10 However, the hyperplasia of the solitarylymph follicles and of the abdominal lymph nodes differed in no wayfrom that seen in many acute infectious diseases in childhood. Micro-scopically there was no evidence of acute inflammatory change in thevicinity of the lymph follicles. There were, however, occasional smallfoci of necrosis of germinal centers. It is also noteworthy that theolder patients in this series did not have this lymphoid hyperplasia.

SUMMARYThe findings at necropsy of I 7 patients dying from poliomyelitis are

recorded. The changes in brain and spinal cord were not unusual andare given only cursory mention. In ten instances myocarditis wasfound. It was detected only on microscopic examination and variedgreatly in extent and severity. Often it was noted in the vicinity ofminute or larger epicardial or endocardial petechial hemorrhages.Myocarditis was apparently in no way related to pneumonia or totherapeutic measures. The sudden death of some of these patientsmay be attributed to the myocarditis. Interstitial pneumonia was en-countered six times. It is possible that the pulmonary lesions werecaused by a virus. Bronchopneumonia was present five times. Hyper-plasia of the lymph follicles and Peyer's patches, although almost con-stant in children, is not an important feature and is not characteristicof poliomyelitis. REFERENCES

i. Dublin, W. B., and Larson, C. P. Pathologic findings in poliomyelitis. Am.J. Clin. Path., 1943, I3, I5-17.

2. Larson, C. P. Pathology of poliomyelitis. Northwest Med., I94I, 40, 448-450.

VISCERAL LESIONS IN POLIOMYELITIS 105

3. Stone, W. J. The heart muscle changes in pneumonia, with remarks on digi-talis therapy. Am. J. M. Sc., 1922, I63, 659-68.

4. French, A. J., and Weller, C. V. Interstitial myocarditis following the clinicaland experimental use of sulfonamide drugs. Am. J. Patk., I942, I8, 109-121.

S. Ratner, B. Allergy,A and Immlmotherapy. Williams & WilkinsCo., Baltimore, I943, p. 3.

6. Hertz, A. F., Johnson, W., and Depree, ]L T. Case of polioenealomyelitisaiated with optic neuritis and myocarditis. Guy's Hosp. Rep., I9I3, 67,105-107.

7. Saphir, O., and Wile, S. Myocarditis in poliomyelitis. Am. J. M. Sc., I942,203, 781-788.

8. Peale, A. R., and Lucchesi, P. F. Cardiac musde in poliomyelitis. Am. J. Dis.Child., 1943, 65, 733-738.

9. Hassin, G. B. Landry's paralysis: its clinical and pathologic featmues. J.Newopath. & Exper. Newol., 1943, 2, 293-300.

Io. Burrows, M1 T. Is poiomyelitis a disease of the lymphatic system? Arch.Jxt. MCd., I931, 48, 33-50°

For additional references that may be costed, see also Infantile Paralysis: ASymposium Delivered at Vanderbilt University, April, 1941. Pulibshed bythe National Foundation for Infantile Paralysis, Inc., 120 Braway, NewYork City.

[I ustrtion folow]

DESCRIPTION OF PLATES

PLATE i6

FIG. I. Heart with inflammatory cells principally in the interstitial tissue. Mostof the cells are lymphocytes but a few polymorphonuclear leukocytes arepresent also. Iron-hematoxylin and eosin preparation. X iso.

FIG. 2. Severe degeneration of myocardial fibers with diffuse infiltration of inflam-matory cells, mainly polymorphonuclear leukocytes. Iron-hematoxylin andeosin preparation. X I30.

FIG. 3. Myocardium. Inflammatory cells are located principally in the interstitialtissue. The inflammatory cells are both lymphocytes and polymorphonuclearleukocytes. Iron-hematoylin and eosin preparation. X 80.

FIG. 4. Heart with heavy infiltration of polymorphonuclear leukocytes and lympho-cytes. Iron-hematoxylin and eosin preparation. X I30.

FIG. 5. A field similar to that shown in Figure 4. Iron-hematoxylin and eosinpreparation. X 200.

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Saphir Vihsceral Lesions in Poliomyelitis107

PLATE I6

PLATE I7

FIG. 6. Aorta, showing edema-like material separating the elastic lamellae and thepresence of few inflammatory cells. Iron-hematoxvlin and eosin preparation.X I20.

FIG. 7. A field similar to that shown in Figure 6. Iron-hematoxYlin and eosinpreparation. X i8o.

FIG. 8. Trachea, showing hyperemia and the presence of lymphocytes and a fewpolymorphonuclear leukocytes within the submucosa. Iron-hematoxylin andeosin preparation. X I40.

FIG. 9. Small bronchus. showing infiltration of the submucosa principally withpolymorphonuclear leukocytes. and extension of the inflammatory cells betweenthe muscle fibers. Iron-hematoxylin and eosin preparation. X I50.

FIG. IO. Interstitial pneumonia. Lymphocytes and a few polymorphonuclear leu-kocytes are present within the septa, while the alveoli are empty. Gienisapreparation. X IIO.

FIG. ii. A field similar to that shown in Figure io. Giemsa preparation. X i8o.

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Saphir Visceral Lesions in Poliomyelitis

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