E A R L Y NEONATAI~ P E R I O I }
t~EPORT OF A CASE
JAMES F. JOI~,,SON, M.D., BIN~HAM~0~, N. Y., A N n P H I L I P M. STI~r M.D., N E W YORK, N. Y. H E virus of poliomyelitis is gen-
T erally believed to enter the human
b o d y by way of tile a l i m e n t a r y canal including tile n a s o p h a r y n x and to travel along nerves to the central nervous system. This belief does not predicate the presence of the virus in the blood stream. However, so-ealled systemic manifestations occurring' toward the end of the normal incubation period might be due to a t e m p o r a r y viremia, and certainly the occurrence of prenatal infection would indicate the passage of the virus to the unborn baby through the placenta f r o m the m o t h e r ' s blood stream. I n this p a p e r is presented a discussion of evidence in the literature t h a t bears on the possibility of a viremia occurring in poliomyelitis, p a r t i c u l a r l y during pregnancy, and a case report of an app a r e n t p r e n a t a l poliomyelitis infection. Poliomyelitis occurs more f r e q u e n t l y in p r e g n a n t women t h a n would be predicted f r o m statistical ehance; the disease occurs in all trimesters, i' ~' a, ~, ~, G The infant is usually normal, although there appears to be an increased incidence of abortions. ~' ~ Autopsies on stillborn infants under these circumstances have failed to reveal evidenee of poliomyelitis) From a stillborn i n f a n t (the mother having' developed p a r a l y t i c poliomyelitis t e n days p r i o r to p a r t u r i t i o n ) , H a r m o n and I~Ioyne~ inoculated a spin.a] cord suspension intracerebrally into monF r o m the New 5~ork ttospital-Cornel] lVfedieal Center, D e p a r t m e n t of Pediatrics.
keys, with negative results. H o r n ~ recently reported 180 eases of poliomyelitis occuring during preg~ancy and reviewed a total of 522 cases reported in the world literature. F r o m this survey and extensive personal experience it was her impression t h a t infants do not contract the disease in utero. Only m~e i n f a n t in her series developed poliomyelitis, oil the tenth d a y of life, the mother having developed clinical signs on the fifth day after delivery. I n the American literature, no authentic instance is recorded in which the clinical picture of poliomyelitis was present in an i n f a n t .at the time of birth.S, 9, ~ Baskin and associates u found seven reported instances of poliomyelitis developing in the neonatal period, with corrobmative clinical and laboratory findings. They presented an infant (the mother having acute paralytic poliomyelitis of four d a y s ' duration at the time of the birth), who developed fever at 31/2 days, and died on the seventh day of life. A u t o p s y revealed lesions charaeteristic of acute polioeneephalomyelitis. Tissues f r o m the infant produeed lesions typical of poliomyelitis, in C y n o m a l g u s monkeys. B a s k i n ~ located only one other infant (reported by F r o v i g ~2) in whom the clinical symptoms developed prior to the fifth day of life. Kreibich and Wolf in Germany, ~a in 1950, reported a newborn infant who had repeated asphyxial attacks, showed
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marked flaccidity of the extremities, and died twelve hours after birth, the mother having developed poliomyelitis three weeks before parturition. Examination of the spinal cord revealed lesions characteristic of poliomyelitis. These reports have more than academic significance. The minimal incubation period of the disease in human beings has been generally estimated to be five days. *~, *~ Instances of poliomyelitis in which symptoms begin before the fifth day of life must have had an incubation period less than this commonly accepted minimum or the infants must have been infected transplacentally. Transplacental infection would imply that the virus was transmitted through the niother's blood stream. Poliomyelitis virus has been demonstrated in the blood of experimentally infected monkeys in isolated instaneesf~, ~6, ~, ~s Melniek~9 recovered a single strain of the virus from-the blood of four of ten monkeys .after intracerebral and/or intraperitoneal inoculation. German and Trask, ~~ in rhesus monkeys, severed all cutaneous, muscular, and nervous connections (including periarteriaI sympathectomy) of .an entire leg, leaving only the femur, femoral artery, and vein; following inoculation into the skin of the extremity, generalized poliomyelitis developed even more rapidly than in normal animals. All workers agree that correlation of'the pathogenesis of poliomyelitis in experimen"cal animals (usually introduced by intracerebral or intraperitoneal inoculation) with the naturally occurring disease is not strictly .valid because of the highly artifieiM methods usually necessary to induce experimental infection.
Recovery of poliomyelitis virus from human blood has been recorded twiceY ~,~ Ward and collaborators demonstrated poliomyelitis virus in one of 111 eases of paralytic and abortive poliomyelitis. Jungeblut points out that in only twenty of these was the blood drawn on the first day of the elinieM disease and that only two of this group were of the paralytic type. The single positive specimen was obtained a few hours after the onset of symptoms in a child with abortive poliomyelitis. From the blood of a patient with the clinical picture of mild paralytic iooliomyelitis/ Koprowski and associates reported isolation from the blood of an agent having the characteristics of poliomyelitis virus. Because of the extreme rarity of this finding, Ward and co-workers doubted its importance in the pathogenesis of the human disease. They were inelined to ascribe instances of visceral involvement or viremia to overflow of virus from. actively involved tissues. Jung'eblut ~, ~ believes that viremia probably exists.in the early stage of infection. Following the experiments of Howe and Bodian, ~ most authors agree that, once in the nervous system, the virus proceeds along nervous pathways. The frequent dem.onstration of viscerM lesions in human poliomyelitis, and their demonstration i~. experimental animMs even with standard strains of poliomyelitis virus 23 have seriously challenged the concept of strict neuro~ tropism. These observations suggest that generalized dissemination of the virus occurs early in tile pathogenesis of the human disease. The recent report of Wenner and Rabe, ~6 in which poliomyelitis virus was demonstrated in the lymph nodes of six of nine pa-
tients dying of poliomyelitis, supports this idea. These authors suggest that the virus m a y be absorbed through the intestinal wall and pass by the intestinal lymphatics to the blood stream and interstitial tissues, and later localize in l y m p h nodes and nervous tissue. The question of hematogenous dissemination is closely related t o current work on classification of poliomyelitis v i r u s . 2 3 , 24, 27, ~s, ~9 W h e r e viruses such as Coxsaekie and the eneephalomyoearditis (EMC) groups stand in relation to poliomyelitis and the eneephalitides r e m a i n s to be demonstrated. CASE REPQRT
W. W., New York Hospital No. 584203, a white female infant, was admitted on Oct. 19, 1950, at the age of 5 days, by t r a n s f e r f r o m the hospital of b i r t K The chief complaint was paralysis of the legs and abdomen. She was said to have been born spontaneously .at term and to have cried spontaneously; no cyanosis had been noted and the early neonatal period was supposedly uneventful. She was examined for the first time on the f o u r t h d a y of life, at which time the referring pediatrician found weakness of the right side of the abdomen and the right thigh, without other pertinent physical findings. The mother, aged 39 years, had a miscarriage in 1945, cause unknown; the second p r e g n a n c y in 1947 resulted in a normal child. D u r i n g the present pregnancy, the mother h a d been well until six weeks prior to delivery, when she developed pain in the muscles of her back and shoulders, followed in a few days by the symptoms of a mild coryza. These symptoms subsided gradually during the next two weeks and during the last month of the p r e g n a n c y she seemed well. The sibling had s y m p t o m s of coryza at the same time as the mother. Further questioning revealed that a boy in the a p a r t m e n t house in which the family lived developed poliomyelitis during
this period, six weeks prior to the bil~ch of this infant; one week later, five weeks prior to the birth, the brother of this boy a]so developed para]ytie poliomyelitis. There was no f u r t h e r pertinent family history. E x a m i n a t i o n on admission revealed a 3,800-gram infant in good general condition. Most strikingly, the midportion of the right abdomen bulged laterally when she cried. The lower extremities were maintained in a froglike position. She appeared to be able to extend both thighs, but was unable to adduet the hips or to flex the hips f u r t h e r t h a n that entailed by the frog position. No knee or ankle jerks could be elicited. The u p p e r extremities seemed normal, and the biceps and peroneal reflexes were normnl. Response to p i n p r i c k was present. There were no other abnormal findings. The peripheral hemogram on admission revealed hemoglobin 18.2 grams; red blood count 5.4 million; ~ h i t e blood count 10,400, with Iymphoeytes 60 per cent, monoeytes 2 per cent, bands 4 per cent. Urinalysis was normal. IVIazzini test was negative on Oct. 20, 1950. Sedimentation rate on October 26 was 16 mm. per hour; on November 10, 21 mm. per hour. P r o t h r o m b i n time was 63 per cent of adult normal; bleeding time 1 minute 20 seconds; clotting time (capillary) 5 minutes 35 seconds on November 6. U r e a nitrogen was 24 mg. p e r cent; blood sugar 68 mg. p e r cent; serum protein 5.7 Gm. per cent; serum calcium 10.0 mg. per cent; serum phosphorus 6.9 rag. per cent; serum carbon-dioxide combining power 25.3 m.mols p e r liter; serum chlorides 112.0 meq. per liter; serum potassium 5.8 meq. p e r liter; serum sodium 138.3 meq. p e r liter. Serological test for toxoplasmosis was negative (Dr. Heinz Eiehenwald). Nose and throat culture revealed the usual flora.; stool culture, no pathogens. Spina.1 fluids on October 20 were crystal clear, with 16 white blood cells per cubic millimeter, 100 p e r cent lymphoeytes; sugar 34 rag. p e r cent; protein 169 rag. per cent; culture nega-
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live; Wassermann negative; Pandy 2 plus. On Octpber 23, crystal clear, following bloody tap; 159 fresh red blood cells, 10 white blood cells per cubic millimeter; protein 160 rag. per cent; culture negative; Pandy 1 pins. On October 30, clear, faintly yellow; red blood cells 160, 8 white blood cells per cubic millimeter; protein 123 rag. pet' cent; Pandy 1 plus. On November 10, crystal clear; 270 fresh red blood cells, 6 white blood cells per cubic millimeter; sugar 54 mg. per ten.t; Pandy I plus. Physical examinations during hospitalization continued to reveal a weakness of the abdominal wall on the right side and weakness of adduction of both thighs. Examination on October 24 showed absent knee jerks and ankle jerks bilaterally, and weakness of hip adduction, greater on the right side than left; hip flexion and abduction seemed normal bilaterally. There was also weakness of knee extension bilaterally; the feet moved normally. After hospital release, the infant was followed in the Department of Physical Therapy for the supervision of home exercises. At 6 weeks of age, there was residual weakness of the right abdomen and left thigh. At 10 weeks of age the abdominal reflexes appeared normal, and there was no bulge; there was still slight weakness in addnetion of the left hip and limitation in extension of the left knee. When seen at the age of 6 months, only the residual weakness in the left lower ex.. tremity persisted. In the laboratory of Dr. Robert 9 Ward, suspensions of a stool specimen from this infant, taken during the first week of hospitalization, produced no disease when injected intracerebrally into monkeys. COMMENT
In the face of negative results with intraeerebral inoculation of the stool suspension into monkeys and negative spinal fluid and routine cultures, the diagnosis remains unproved in this in-
rant showing m.ild paralysis with sub-. sequent almost complete recovery. The unusual history, the fact that the birth occurred toward the close of a poliomyelitis epidemie, the pleocytosis and increased albumin content of the spinal fluid, with subsequent fall in these values, and the selective flaccid paralysis of certain skeletal muscle groups of tile abdomen and extremities, with later improvement, make the probable diagnosis poliomyelitis. No examination of tlle infant was performed at the time of birth but the fact that the entire postnatal course of this infant was asymptomatic and afebrile, suggests that the paralysis may have been present unnoted at birth: intrauterine infection may have occurred at the time of the illness of the mother, six weeks ante tiartmn, lit is well known that pleocytosis and increase in albumin content in the s p i n a l fluid may persist for many weeks following the acute phase of the illnessY ~ If this is indeed an instance of poliomyelitis, it would appear to be the first instance recorded of poliomyelitis in the early neonatal period in which the mother was clinically well during and following parturition. SUMMARy
The case history is presented of an infant showing the elinieaI picture of paralytic poliomyelitis at the time of the first physical examination on the fourth day of life. Laboratory data, particularly the spinal fluid findings, were consistent with although not completely confirmative of this diagnosis. The ante-partum history and the clinical .features of the ease suggest that this may have been an intrauterine infection. Based on this report and a discussion of the literature, the by-
JOHNSON AND STIMSON: t ) o t h e s i s is s u g g e s t e d c l i n i c a l l y t h a t a viremia may at times be present in poliomyelitis.
1. Brahdy~ M. B., and Lenarsky~ M.: Acute E p i d e m i e Poliomyelitis Complicating Pregnancy, J. A. 1V[. A. 101: 195, 1933. 2. Kleinberg, S, and Horwitz, T.: The Obstetric Experiences of Women Paralyzed by Acute Anterior Poliomyelitis, Surg., Gynee. & Obst. 72: 58, 1941. 3. Weaver, H. M., and Steiner, G.: Acute Anterior Poliomyelitis During Pregnancy, Am. J. Obst. & Gynee. 47: 495, 1944. 4. Baker, M. E., and Baker, I. G.: Acute Polimnyelitis in Pregnancy. Minnesota Med. 30: 729, 1947. 5. [[Iorn, P . : Pregnancy Complicated by Anterior Poliomyelitis, Ann. West. Med. & Surg. 5: 93, ]95]. 0. Weinstein, L., Aycoek, W. L., and Feemster, R . F . : The Relation of Sex, Pregnancy and Menstruation to Susceptibility in Poliomyelitis, New England J. Med. 245: 54, 1951. 7. Harmon, P. II., and Hoyne, A.: Poliomyelitis and Pregnancy, J. A. M. A. 123: 185, 194g. 8. Mouton, C. M., Smillie, J. G., and Bower, A.G.: Report of Ten Cases of Poliomyelitis in I n f a n t s Under Six Months of Age, J. PEDI~.T. 36: 482, ]950. 9. Baskin, J. L., Soule, E. II., and Mills, S. D.: Poliomyelitis of the Newborn, Am. J. Dis. Child. 80: 10, 1950. 10. Shelokov, A., and Weinstein, L.: Poliomyelitis in the Early Neonatal Period: Report of a Case of Possible Intrauterine Infection. J. P~DIAT. 38: 80, 1951. 11. Baskin, J . L . : Poliomyelitis of the Newborn (Correspondence), Am. J. Dis. Child. 80: 999, 1950. 12. Frovig, A. G.: Poliomyelitis in Mother and Newborn Child With Multiple Appearances of the Diseas% Nord reed. 34: 1115, 1947. 13. Kreibiet b tI., and Wolf, W.: Ueber einen Fall yon diaplazentar Poliomyelitis Infektion des Feten in 9. Schwangersehaftsmonat~ Zentralbl. f. Gyniik. 72: 694, 1950. 14. Casey, A. E.: The Incubation Period in Epidemic Poliomyelitis, J. A. lVf. A. 120: 80G 1942. 15. F]exner, S., and Lewis, P. A.: Experimental Epidemic Poliomyelitis in Mow keys, J. Exper. Med. 12: 227, 1910. 16. Zappert, J., yon Wiesner, R., and Leiner, K.: Studien fiber die tteine-Medinsche t(rankheit, Leipzig and Wien. 1911, F.
Deutieke, p. 171 (quoted by Clark and associates*r). Clark, P. F , Fraser, F. g., and Amoss~ H.L.: The Relation to the Blood of the Virus of Epidemic Poliomyelitis~ J. Exper. Med. 19: 223, 1914. Sabin, A. B., and Ward, R.: Insects and Epidemiology of Poliomyelitis, Science 95: 300~ 1942. Melniek, J. L.: Poliomyelitis Virus in the Blood StreaIn in the Experimenta] Disease, Pron. Soc. Exper. Biol. & Med. 58: 14, 1945. German, W. J , and Trask, J . D . : Cutaneous Infectivity in Experimental Poliomyelitis; Increased Susceptibility After Neurosm'gieal Procedures, J. Exper. ~ed. 68: 125, 1938. Ward, R., Horstmann, D. M., and Melniek, J.L.: Tile Isolation of Poliomyelitis Virus From Human Extra-~eural Sources. YV. Search for Virus. ln the Blood of Patients, J. Clin. Investigation 25: 284, 1946. Koprowski, 7H., 2#orton~ T. W , and McDermott, W.: Isolation of Poliomyelitis Virus From H u m a a Serum by Direct Inoculation Into a Laboratory Mouse, Pub. tIealth Rep. 62: 1467, 1947. Jungeblut, C'. W.: Newer Knowledge on the Pathogenesis of Poliomyelitis, J. PEDIAT. 37: I09, ]950. Jungeblut, C. W.: Further Experiments With Columbia SK Marine Poliomyelitis Virus, Bull. lkTew York Aead. Med. 26: 571, ]950. tIowe, H. A., and Bodian, D.: Neural Mechanisms in Poliomyelitis, New York~ 1942, Commonwealth Fund. Wenner, [H. A., and Rabe, E . F . : The Recovery of Virus From l~egional Lymph Nodes of F a t a l Biuman Cases of Poliomyelitis, Am. J. M. So. 222: 292, 1951. Paul, J. R.: Immunologic Types of Poliomyelitis Viruses. In: Poliomyelitis, Papers and Discussions presented at the First International Poliomyelitis Conference, Philadelphi G 1949, J. B. Lippincott Co., p. 2771. Pappenheimer, A. M., Daniels, J. B., Cheever, F. S., and Weller, T. 7K.: Lesions Caused in Suckling Mice by Certain Viruses Isolated From Cases of Socalled Non-Paralytic Poliomyelitis and of Pleurodynla~ a. Exper. MYed. 92: 169~ ] 950. Melniek, J. L.: The Poliomyelitis, Eneephalomyoearditis and Coxsaekie Group of Viruses, Bact. Rev. 14: 233, 1950. Andelman, M. B., Fishbein, W. I , and Casey, A. E. : Spinal Fluid Protein in the Retrospective Diagnosis of Subeliuieal Poliomyelitis, South. M. J. 39: 706, 3946.