Total absence of the cerebral hemispheres

T O T A L A B S E N C E OF T t t E C E R E B R A L H E M I S P H E R E S REPORT OJ0' TWO CASES

ELOISE EBEaLING JOm~SON, M.D., MAUY WAaNER, M.D., AND J. P. SIMONDS, M.I). CHICAGO, ILL.

OTAL absence of the cerebral hemispheres is a very rare congenital anoinaly. Two cases of this condition, both associated with arhinencephaly, were studied by us in this hospital between 1944 and 1947. Because of its rarity and because of the difficulties in differential diagnosis, it seems worth while to report them. Various names have been applied to this condition, such as "cerebral agenesis" (Riese, ~ Savatier, 2 H u t i n a P ) , "aplasia of the cerebral hemispheres" (Grawitz~), and "hydranencephaly" (Watson, ~ following the terminology of Cruveilhier~). Casainajor ~ w a s satisfied with the title of "a child without a f o r e b r a i n . "

T

Author Cruvelihier tturowitz Lieen Ilberg Spiehneyer Spielmeyer Bettinger Watson t:[aler Watson Johnson, Warner, Simonds Riese Johnson, W a r n e r Simonds Watson Casamajor Edinger and Fischer

Year of Publication

A g e of Pat~ent~

1856 1936 ] 921 1899 1905 1905 1942 1946 1934 1944

StiUborn Stillborn Newborn 6 days 1 week 1 week 1 week I week 2 weeks 18 days 20 days

1934

3 weeks

1944 1937

40 days 251~ too. 3 yr.

1913

3 yr. 9 too.

Cruveilhier's case is the first record of this condition to which we had access. This was a stillborn infant. The entire mass of its brain was represented by a delicate membrane in the anterior and middle fossae of the skull and a globular mass which lay beneath the intact tentorium cerebelli. He believed that this case was one of hydrocephalus and anencephaly combined in one congenital anoInaly. Hence the name " h y d r a n e n e e p h a l y , " but in his earlier publication, he designated it as " c y s t a n e n c e p h a l i e . " The reports of Inost of the cases in the literature are very brief with relatively few clinical or pathological details. As Riese 1 has pointed out, most of the authors have been more interested in the portions of tile brain that were lacking than in those that were present. No detailed descriptions are

This group does not include such obvious monstrosities as cranioschisis. Also omitted from our collection of cases from the literature are those of Grawitz 4 and of Minekler and his coworkers, s which, although they resemble our cases in m a n y respects, presented certain differences that seemed to justify their exclusion. Articles by Savatier ~ and by Hutinal '~ on "ag6n6sie c6r6brale" and V i a n a ' s 9 paper on " h y d r a n e n c e p h a l y " were not accessible to us. We have accepted the following eases as probably belonging in the category with ours: From the Department of Pathology of Children's Memorial Hospital and the Otho S. A. Sprague Institute. 69

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available of tile tracts and nuclei in the residual brain substance, the medulla, or the cord. Riese ~ described briefly a " p r e c o c i o u s " and excessive myelinization in the brain stein in his case. Total absence of the cerebral hemispheres is incompatible with life and the infants usually survive for only a short time. Cruveilhier's + and Hurowitz's ~~ cases were stillborn, the latter b e i n g delivered b y eranioclysis. Licen's ~ ease was a " n e w b o r n . " IIb e r g ' s ~2 patient was a 6-day-old infant whose cerebrum was absent anterior to the corpus cal]osmn, the m a m m i ] l a r y bodies, the fornix, and the pineal gland. Spielmeyer TM reported t w o eases of this a b n o r m a l i t y in nonidentical t~dns that survived for about a week. B e t t i n g e r ' s 1+ and one of Watson's 5 patients lived 1 week each; H a l e r ' s ~ for 2 weeks; and another of W a t s o n ' s ~ for ;/8 days. Tile infant described by Riese I lived for three weeks. I n an addendmn to his p a p e r Watson '~ mentions an i n f a n t with this condition that survived for 2 5 8 9 months. C a s a m a j o r ' s + patient lived for 3 years and that of E d i n g e r and Fischer, ~ for 3 years, 9 months. Both the latter children developed marked muscular rigidity that had some of the characteristics of decerebratc rigidity. In our two eases the infants lived for 20 and 40 days, respectively. Among the sixteen .eases tabulated and summarized above, two were stillborn, eleven died within 1 month, and three survived for 2 5 8 9 months to 3 years, 9 months. In nine of the eleven eases in which death occurred in less than one month and in which clinical data were available, the behavior of the infants was essentially normal for the age. F o r d ~ quotes L a n g w o r t h y

OF P E D I A T R I C S

to the effect that, " T h e reflex activity of the newborn h u m a n infant could all be mediated by reflexes involving the b r a i n stem and spinal elements which have already acquired their myelin sheaths. Indeed, m a n y p a t h w a y s at b i r t h are well medullated as high as the u p p e r end of the midbrain, and the behavior of the newborn i n f a n t is essentially that of a brain stem preparation." According' to l~ord, 17 a n u m b e r of reactions arc elicited u n d e r normal conditions during only the first few months of life; that is, when the lack of myelinati0n prevents cerebral inhibitions. M a n y of these are characteristic of decerebrate p r e p a r a tions. The heads of all the above patients were a p p r o x i m a t e l y of normal size, except ~hat of Cruveilhier, a in which the head was small, and of Hurowitz, ~~ in which the head was so large that delivery required cranioclysis. The cerebral hemispheres were totally absent except possibly in the case of Riese. ~ The midbrain was defective. In most of the cases the c e r e b e l h m and pons were normal, except that in one of our patients the cerebellum was malformed. Several authors m e n tioned arhinenccphaly which w a s present in both of our eases. CASE RE.PORTS CAS~ 1 . - - T h i s white male infant, born Jan. 21, 1944, by breech delivery, was admitted to Children's Memorial Hospital in a m o r i b u n d state with slow, shallow respirations and a history of slow gain in weight. Physical examination revealed a 20day-old, small, flaccid white male inf a n t with a moderately large eggshaped head and an icteric tint to the skin. The head circumference was 1 4 ~ inches; the fontane]s were widely open and the suture lines separated.

JOHNSON

ET AL. :

TOTAL ABSENCE

The cornea of the left eye was opaque and the left pupil was pin point in size and fixed. Lateral nystagmus was observed and the reflexes were hypoactive. Diagnostic impressions were: (1) mild hydrocephalus ; (2) bilateral intrauterine corneal ulceration with secondary iridoeyelitis. Treatment consisted of C0ramine and adrenM cortical extract in addition to tile usual routine orders. Course in the Hospital.--The temperature remained subnormal. In the

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I-IElVIISPI~IERES

71

poplasia of the adrenals, congestion of the lungs, liver, spleen, and kidneys. The head appeared moderately enlarged and measured 36 era. in circumference. Both fontanels were widely patent and the anterior one 8 era. across. The lambdoidal and sagittal sutures were separated, the former by a space of about 8 ram. The scalp was retracted in the usual manner. The calvarium was opened by cutting along the suture lines. As the scissors blade penetrated the anterior fontanel,

Fig. 1 (Case 1).--Base of t h e s k u l l w i t h t h e r u d i m e n t a r y b r a i n in place. T h e t h i n m e m b r a n e w h i c h l i n e s t h e i n n e r s u r f a c e of t h e d u r a m a t e r c o n t a i n s m a n y s m a l l h e m o r r h a g e s . T h e r i g h t h a l f of t h e t e n t o r i u m of t h e c e r e b e l l u m is m a r k e d l y f e n e s t r a t e d .

first twenty-four hours, the patient had fourteen bowel movements, did not cry, but was noted to have a sucking reflex and swallowed. The baby remained in a moribund state, became apneie on the second hospital day, and died despite stimulants. Su~r~mary of Patholog~.--The important findings were limited to the brain, and these will be described in detail. Other pathologic changes were e a r l y bilateral bronehopneumonia, hy-

xanthochromic fluid poured from the opening. It was estimated that the cranial cavity contained 250 c.e. of similar fluid. The brain could not be palpated through the opening in the fontanel. The only evidence of a brain was a small walnut-sized structure reposing on the floor of the cranial cavity. The dura mater lined the inner table of the ca]varium, and was irregular, thick, and pearly-gray with small trabeculae. The anterior,

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middle, and posterior fossae and the roofs of the orbits were well formed. The brain tissue, resembled two halves of a large walnut. Removal of the tentorium revealed a small cereb e l h m extending downward and posteriorly. The entire spinal cord and

OF P E D I A T R I C S

the mass of brain tissue on the base of the skull were removed in one piece. The weight of the entire structure was 28 grams, i.e., less than 10 per cent of the normal weight of these organs for an infant of this age (382 grams). When the "nubbin" of a brain was

Fig'. 2.

. F i g . 3. ]~'ig. 2 ( C a s e 1 ) . - - U p p e r ~ig. 3 (Case 1).--Under

surface of the rudimentary s u r f a c e of t h e r u d i m e n t a r y

brain. brain.

JOHNSON

ET AL. :

TOTAL ABSENCE OF CEREBRAL H E M I S P H E R E S

removed, a tiny pair of optic nerves were seen extending f r o m a small aptic chiasm to the optic tracts. The basilar a r t e r y and the junction with the two vertebral arteries were identified, but the internal carotid arteries were not found. Attached to the dorsal aspect of the pons was a small cerebellum represented by one small lobe, and anterior to it the lamina quadrigemina. More a n t eriorly, two lateral masses were identified as the thalami and the corpora striata. The left one was larger. Attached to these masses were two soft freely movable red strands, the choroid plexus. The anterior thalamic tubercles were barely recognizable. Surrounding the specimen was a torn rim of tissue identified as meninges. There was no gross abnormality of the spinal cord except that it was unusually narrow. The olfactory nerves and the rhinencephalon were absent, but the other eleven pairs of cranial nerves could be seen extending from a fairly wellformed, small brain stem. No microscopic sections were taken. Diagnosis: (1) Arhinencephaly with total absence of the cerebral hemispheres; (2) partial agenesis Of the cerebellum; (3) hypoplasia of the adrenals; (4) absence of the internal carotid arteries; (5) acute bilateral bronchopneumonia; (6) corneal opacity of the right eye (congenital); (7) xanthochromie pleural, pericardial, and peritoneal effusions; (8) congestion of the lungs, spleen, liver, and kidneys. CASE 2.--This white female infant was admitted to the Children's Memorial Hospital on Nov. 29, 1947, at the age of 1 month, because of cyanotic spells with stiffness of the extremities, failure to eat and unusual downward gaze all of one day's duration. The i n f a n t was a six-week p r e m a t u r e baby; weight at birth was 4:5 pounds. F o r approximately one week after birth, the baby required oxygen because of persistent cyanosis. The patient had been hospitalized elsewhere for two

~3

weeks prior to tile present admission and had never cried loudly. Physical examination revealed a small 1-month-old white female i n f a n t weighing 5 pounds, 3 8 9 ounces, and having a moderately large head. The infant had good color. The arms and legs were spastic. The fontanels were open, large, and tense. There was separation of the suture lines of the skull. The circumference of the head was 1 3 ~ inches. Percussion of the skull gave a tympanitie note. The liver was palpable. The reflexes were hyperactive, and bilateral ankle elonus was demonstrated. Clinical impression: (1) -birth i n j u r y - - s u b d u r a l hematoma; (2) hydrocephalus. Treatment consisted of gavage feedings and daily subdural taps. On admission a spinal tap was done: pressure normal; P a n d y test 3 plus; spinal fluid was clear, and cell count 7. A subdura] tap was done on admission and 25 c.e. of xanthoehromic fluid were removed; 15 e.c. from the left angle of the anterior fontanel, and 10 c.c. from the right. Following the subdural taps, the condition seemed to improve temporarily; the respirations were slightly deeper and the heart rate increased toward normal. Breathing again became shallow and the patient was placed in oxygen. Examination revealed depressed breath sounds throughout the entire chest with associated r~les. Several subdural taps were done and approximately 15 c.e. were removed at each time. On examination of the fundi no retinal hemorrhages were seen. Because of the yellow subdura] fluid, a diagnosis of toxop]asmosis was considereal. Three-tenths cubic centimeter of sediment from the spinal fluid was injected intraperitoneally into each of six white m~ce and all remained healthy. No toxop]asma organisms were found in the sediment from the spinal fluid. The patient became moribund and expired on the seventh hospital day. Summary of Pathology.--The important pathologic findings in this case were limited to the brain which will

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be described in detail. Other pathologic changes include confluent bronchopneumonia which was probably the immediate cause of death, hypoplasia of the adrenals, passive congestion of the liver and spleen, accessory spleen and follicular cysts of the ovaries. The head was normal in shape and measured 32.5 era. in circumference. The anterior fontanel was 4 cm. in its greatest diameter, was slightly bulging and tense, but the cranial sutures were not widened. The small veins of the scalp were prominent. I n the skin over the anterior fontanel was an area of purplish discoloration 4 cm. in diameter and several needle puncture marks. The vertex of the skull was exposed by the usual mastoid-to-mastoid incision through the scalp. I n the scalp beneath the purplish area previously mentioned there was a dark red hemorrhage into the tissues. The skull was opened by cutting along the various sutures and the bony plates were pressed outward. Upon puncturing the m e m b r a n e composing the coronal suture, reddish-brown fluid escaped. The skull cavity was filled with an estimated 300 c.c. of this fluid. The only evidence of the presence of a brain was two elongated masses lying on the base of the skull and measuring about 1.5 x 2 x 3.5 cm. on the left side and I x 1.5 x 2.5 cm. on the r i g h t side. Covering and loosely attached to the inner surface of the dura m a t e r over the vault, sides, and base of the skull was a thin grayish-red membrane which had been cut into segments on separating the bones of the skull along the suture lines. This m e m b r a n e was carefully separated from the inner surface of the skull and was removed with the remnant, of brain to be described later. I t ranged f r o m the thinness of tissue p a p e r up to barely 1 ram. in thickness. Its internal surface was smooth. The falx cerebri and the tentorium cerebelli were present and in their normal locations. The internal carotid arteries were smaller t h a n normal but could be identified. The small r e m n a n t of brain and the m e m b r a n e were removed

OF P E D I A T R I C S

by incising the t e n t o r i u m cerebelli and cutting through the spinal cord well below the medulla oblongata. The above-mentioned membrane, the brain substance above the tentorium, the pens, cerebellum, medulla, a n d a portion of the spinal cord, all removed in one piece, together weighed 46 grams, a p p r o x i m a t e l y 11 p e r cent of the normal weight of the brain of an i n f a n t of this age (422 grams). Upon examining the inferior surface of this specimen, the olfactory nerves and their tracts could not be found. The remaining cranial nerves f r o m the second to the twelfth, inclusive, were all identified (Dr. Magoun, of the Departmerit of Neurology of Northwestern University Medical School). The optic nerves a p p e a r e d to be smaller than normal and measured barely I ram. in diameter. The vertebral and basilar arteries and vessels forming the circle of Willis were present but much smaller t h a n normal. The ehoroid plexus was easily identified and, although somewhat reduced in size, was normal in appearance. The mass which lay above the tentorium of the cerebellum was a bilobed s t r u c t u r e with the left portion larger than the right. The mass on the left measured 1.5 x 2 x 3.5 cm.; its anterior end was rounded; it was pinkishwhite in color; fairly firm in consisteney; and had roughly the shape of the basal ganglia. The mass on the right was shorter and its anterior end was i r r e g u l a r and showed several dimples. I n t h i s mass above the tentorium the following structures were identified (by Dr. Magoun) : the thalamus, hypothalamus, m a m m i l l a r y bodies, and small cerebral peduncles. The pens and cerebellum were present, normal in shape, but smaller t h a n norreal. The polls measured 10 x 12 ram., the cerebellum 2 x 3.5 x 5 era. Above and anterior to the cerebellum and on the dorsal surface, the tectum of the midbrain, the roof of the third ventricle, and one collieulus on each side were identified. I n the pia-arachnoid and in the substance of the cerebellum there were numerous bright red areas

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E T AL. :

T O T A L A B S E N C E OF CEREBRAL H E M I S P H E R E S

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Fig. 4.

Fig. 5. Fig. 4 " ( C a s e 2 ) . - - U p p e r s u r f a c e of t h e r u d i m e n t a r y b r a i n . The thin membrane which l i n e d t h e i n n e r s u r f a c e of t h e d u r a m a t e r r a d i a t e s o u t w a r d f r o m t h e m a s s o f b r a i n s u b s t a n c e . Fig. 5 (Case 2 ) . - - U n d e r s u r f a c e of the r u d i m e n t a r y brain. T h e d i s t r i b u t i o n of b l o o d v e s s e l s in t h e m e m b r a n e s u g g e s t s t h o s e of t h e p i a - a r a e h n o i d . The prominent olivary bodies a r e d i s t i n c t l y visible. T h e s m a l l o p t i c e h i a s m is s e e n n e a r t h e c e n t e r of t h e s p e c i m e n .

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T H E J O U R N A L OF PEDIATRICS

up to 5 ram. in diameter. On the anterior surface of the medulla there was no evidence of the pyramidal tracts, and the olivary bodies projected prominently.

Hypoplasia of the adrenals and kidneys. Accessory spleen. Passive congestion of the liver and spleen.

Microscopic E x a m i n a t i o n . ~ A section of the membrane stripped from the inner surface of the dura mater showed a fine weblike structure in which were several blood vessels. Along a portion of its deeper surface was a thin layer of tissue about 50 to 60 microns thick composed of small round nuclei widely separated by a fine fibrillar material but no ganglion cells. A section from the left or larger mass above the tentorinm was composed of glial tissue with a very few ganglion cells (only three found in this section). The basal ganglia were therefore very imperfectly developed. In a section of the cerebellum there was considerable recent hemorrhage both in the pia-arachnoid spaces and in the substance of the cerebellum itself. In areas not involved by the hemorrhage the cerebellum consisted of the usual three cortical layers, and the Purkinje cells appeared normal in size, shape, and number. ~ The choroid plexus in sections was normal i n structure and in appearance except that the epithelial cells covering the papillary processes contained much brown granular pigment. In a section of the upper cervical cord, the posterior columns were well developed, and the descending tracts were small. The lateral corticospinal tracts could not be identiffed. The gray matter of the posterior horns was relatively abundant; that of the anterior horns was normal in appearance.

The two cases which came to autopsy in this hospital showed striking similarities. Clinically: the patients surrived 20 and 40 days, respectively. There was a history of weight loss, respiratory distress, and feeding problems. Physical examination in both infants demonstrated nystagmus. The patient in Case 1 had a subnormal temperature. The patient in Case 2 showed some evidence of spasticity. Pathologically these two infants were almost identical. The olfactory nerves and tracts (rhinencephalon, archipallium) and the cerebral hemispheres (telenccphalon, neopallium) were absent; that is, portions of both lower and higher parts of the brain failed to develop. Arhineneephaly has been reported with other anomalies of the brai~. Shryock and his co-workersis found it associated with agenesis of the corpus cal]osum and with porenccphaly. It has been suggested that cases such as the ones here reported are extreme grades of porencepha]y. Haler, 15 who described very briefly " a specimen of a case of absence of the cerebral hemispheres, in which the infant lived two weeks" ]eft unanswered his own question " I s this a case of extreme porencephaly?" S i n c e porcncephaly is characterized by the formation of one or more spherical cavities within the brain and since the skull cavity is not itself spherical, the coalescence of multiple cavities w o u l d n o t fit smoothly on the inner surface of the skull. This might, therefore, furnish an explanation for those cases, such

Dic~gnosis.--Arhinencephaly w i t h total absence of the cerebral hemispheres. Itypoplasia of the dieneephalon and mesencephalon, ttypoplasia (or agenesis) of the pyramidal and corticospinal tracts of the spinal cord. Fluid-filled cranial cavity. Pigmentation of the epithelium of the choroid plexus. Multiple hemorrhages in the eerebellmn. Confluent bronchopneumonia. Patent d u c t u s arteriosus.

DISCUSSION

JOHNSON

E T AL. :

T O T A L ABSEI'qCE OF CEREBRAL H E M I S P H E R E S

as C a s a m a j o r ' s 7 and W a t s o n ' s 5 in which a small amount of b r a i n tissue was found in the m e m b r a n e which enclosed the fluid and was loosely attached to the inner surface of the dura mater. I n each of our cases there was a v e r y thin m e m b r a n e which could be separated f r o m the inner surface of the d u r a mater. I n o u r Case 2 in which this m e m b r a n e was examined microscopically it a p p a r e n t l y consisted of glial tissue but nothing resembling ganglion cells was found. These two cases were not simple hydrocephalus, E v e n in extreme hydrocephalus with tremendous increase in the size of the head and enormous dilatation of the lateral ventricles, there is inequality in thickness and therefore in the degree of a t r o p h y of different p a r t s of the cerebral hemispheres. I n our cases, the membrane lining the vertex, lateral aspects, and base of the skull was nowhere more t h a n 1 ram. thick. The same reasons will p r o b a b l y exclude porencephaly as the cause of the condition f o u n d in the brains of the two cases here reported. The presence of arhinencephaly in both patients and of p a r t i a l agenesis of the cerebellum in one infant s u p p o r t the view t h a t the lesion in our eases was on a developmental basis and was therefore a true total agenesis of the cerebral hemispheres. Watson 5 does not agree with this explanation and presents two reasons why agenesis does not explain the absence of the cerebral hemispheres. (1) I n his cases, the brain could be " r e c o n s t r u c t e d " by filling the m e m b r a n e which lined the cranial cavity with cotton. (2) The fact t h a t these infants had fairly n o r m a l a p p e a r i n g skulls indicates, in all probability, that

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the disturbance causing the disappearance of the previously formed cerebral hemispheres began rather late in fetal life, " a c c o r d i n g to Dr. Crosby, about the 5th month of fetal d e v e l o p m e n t . " Thereafter, according to Watson," the brain underwent regression. I t is difficult to conceive of any t y p e of disturbance that could cause such comp]ete regression of previously formed cerebral hemispheres and rhineneephalon. Watson 5 quotes I b r a h a m who described a peculiar type of liquefactive change in brains of the newborn i n f a n t as a result of circulatory changes a n d anoxia. On the other hand, Altschu] 19 has reported the ease of a 9-month-old infant with endarteritis obliterans of the cerebral arteries and m a r k e d a t r o p h y of the brain (16 per cent of normal weight). The cerebral hemispheres were present b u t small. I n both infants the arteries t h a t supply the brain were much smaller than normal, and in Case 1 the internal carotids were not found. I t would be fruitless to speculate whether the brains in these infants failed to develop because of deficient blood s u p p l y or whether the intracranial arteries did not grow because the underdeveloped b r a i n needed relatively little nourishment. I n each of our patients the adrenals were definitely smaller than those in normal i n f a n t s of corresponding age. Small adrenals are also characteristically found in cases of all types of anencephaly. 12 The diminution in the size of the adrenals was due largely to the disappearance of the wide androgenic zone which constitutes a large p a r t of the adrenals of the newborn infant. Angevine ~~ studied eighteen anencephalic monsters and f o u n d t h a t the adrenal glands were small and of

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the adult type 9ecause prenatal a t r o p h y had occurred in the developing adrenal tissue. The clinical and pathological differential diagnosis of cerebral agenesis involves a consideration of at least three diseases: subdural hematoma, toxoplasmosis, a n d hydrocephalus. During the period of hospitalization of the patient in our Case 2, all three of these conditions were considered. 1. Subdural hematoma: An infant with a subdural hematoma may exhibit many of the signs and, symptoms of the eases here presented. There may or may not be a history of birth or other trauma. A baby with a subdural hematoma may be v e r y irritable or may have convulsions; on the other hand, he m a y be stuporous or comatose. Breathing is often irregular, and eyanosis may be present. The reflexes may be hyperactive. Retinal hemorrhages a r e usually present. Bradycardia may occur. The head may be enlarged. F l u i d obtained by subdural tap m a y range from a strawcolor to reddish or red-brown, and may b e obtained from one or both sides. Pneumoencephalogram shows distortion rather than destruction of the brain with or without displacement of the ventricles. Subdural and spinal taps, ophthalmic examination, and pneumoencephalograms are very important aids in the differential diagnosis of subdural hematoma. 2. Toxoplasmosis: We have studied two eases of this disease in this hospital. The diagnosis of toxoplasmosis was considered in Case 2, because xanthochromic fluid is characteristic of toxoplasmosis of the brain. Several attempts Were made to find the microorganism in the spinal fluid sediment, but the tests were all negative.

OF

PEDIATRICS

The characteristic findings of toxoplasmosis are: (1) xanthochromie cerebrospinal fluid; (2) irregular areas of calcification in the brain revealed in roentgenograms ; (3) ehorioretinitis eentralis ; (4) hydrocephalus or microeephaly; (5) convulsions; (6) demonstration of the microorganisms, (a) by smears and (b) b y animal inoculation of sediment from the eerebrospinal fluid. The cerebrospinal fluid shows a high cell count with a predominance of monocytes, increase in total protein, and a decrease in sugar and chlorides. I f materials are available, the neutralizing antibody and complement fixation tests may be done. Since toxoplasmosis in the newborn infant is always the result of intrauterine infection, the symptoms and signs are present at birth and the infant usually dies within a few weeks or months a f t e r birth. Pneumoencephalograms reveal destruction of the brain substance. 3. Hydrocephalus: In this condition the head increases in size with wide separation of the cranial sutures and enlargement of the anterior forttanel. The veins of the scalp may be distended. Nystagmus and convergent squint may be present. An associated spina bifida or meningomyeloeele are frequent associated findings. Reflexes may be exaggerated and the muscles of the extremities rigid. A tympanitic note may be heard over the distended cerebral ventricles. The child is usually mentally retarded and lethargic. A cranial tap yields crystal-clear color1 e s s fluid. Pneumoencephalograms and the dye test may yield useful information. 4. Total cerebral agenesis: In contrast to the above three clinical and pathological entities, an infant with

JOHNSON ET AL. :

TOTAL ABSENCE Ol~ CEREBRAL HEMISPHERES

total cerebral agenesis m a y a p p e a r quite normal f o r a few d a y s or several weeks. Usually the head is not increased in size or only slightly so; the sutures m a y or m a y not be separated, and the fontanels m a y or m a y not be enlarged. A tympanitic note can be elicited over the skull. The child m a y be either irritable or in coma. H y p e r active reflexes and subnormal temp e r a t u r e s are present in some but not in all cases. One or more os the cranial nerves m a y be nonfunctioning. Decerebrate rigidity m a y be present. The intraeranial fluid is xanthoehromic as in tox0plasmosis, but the conclusive differential diagnostic features are (1) the absence of evidence of calcification in the brain by x-ray examination, and (2) failure to find the toxoplasma in the eerebrospinal fluid. SUMMARY

Two eases of total absence of the cerebral hemispheres associated with arhinencephaly are reported. These infants reached the ages 02 20 and 40 days, respectively. The weights of the brains were only 10 and 11 per cent of the normal ~or the age. The differential diagnosis of subdural hematoma, toxoplasmosis of the brain, hydrocephalus, a n d total cerebral agenesis is discussed. REFERENCES 1. I~iese, W.: Sur l'ag6n6sie c6r~brale: aggn~sie crois~o du cervelet et des noyaux centrale: myelinlzation precose des systemes conserves, L ' E n c e p h a l e 29: 466~ 1934. 2. Savatier: Observation d~ag6n6sie edr~brale sans deformation de la tote, Clin. de hop. de Pari.s 2: No. 79~ 1827.

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3. H u t i n a h Ag6ugsie e6r6brale, Rev. internat, de reed. et de ehlrurg. 20: 301, 1909. 4. Grawitz: Ein Fall von Aplasie der Orosshirnhaemisphaeren, Deutsche reed. Wchnschr. ,17: 146, 1891. 5. Watson, E. J:L" ttydranencephaly, Am. J. Dis. Child. 67: 282~ 1944. 6. Cruveilhier, J.: Anatomle pathologique du corps humaine, xxxix e Livraison, pp. 1 and 2, Planehe iv, Fig. 2, Paris 182942: and Trait6 d ' a n a t o m i e pathologique g~n6rale 3: 164j 1856, Paris. 7. Casamajor, L.: A Child Without a Brain, Tr. Am. Neurol. A. 63: 64~ 1937. 8. MincMer, J., McCurdy, T., and Iverson~ J . C . : N e b r a s k a M. J. 26: 131, 1941. 9. Viana, J. F.: tIydranencephalus; Cases, Roy. todd. panam. 1: 476, 1945. 10. tturowitz, J.: Ueber einen ungewoehnlichen Fall yon tIydromereneephalie, Sehvceiz. Arch. f. Neurol. u. Psyehiat. 38: 207, 1936. 11. Licen~ E.: Ueber elnen Fall yon Grosshirnmangel bei geschlossenen Schaedel, Ztschr. f. d. ges. Neuro]. u. P s y e h i a t . (Orig.) 64: 282, 1921. 12. Ilberg: Fehlen des Grosshirn a n d As ~ symmetrie der andere IIirnteile bei einem 6-taegigen Kind mit ausgebildeten Schaedel a n d mit Aplasle die Nebennieren, Arch. f. Psyehiat. 32: 1022, 1899. 13. Spielmeyer, W.: Arch. f. Psychiat. 39: 807, 1905. 14. ]3ettinger, It. F.: M. J. Australia 2: 375, 1942. 15. Haler, D.: Specimen from a case of absence of the cerebral hemispheres in which the i n f a n t survived for two weeks, Proe. Roy. Sot., London 28: 1075, 1934-35. 16. Edinger, L., and Fischer~ B.: Ein Mensch ohne Grosshirn, Arch. f. d. ges. Physiol. 152: 535, 1913. 17. Ford, ~'. R.: Diseases of the Nervous System in Infancy, Childhood and Ado]escence, Springfield, Ill., 1944, Charles C Thomas, pp. 5, 58. 18. Shryock, E. H , Barnard, J. F., and Knighton, R. S.: Agenesis of the C~)rpus CaUosum Associated With Poren~ eepha]y: Report of a Case~ Bull. Los Angeles Neurol. Soc. 5: 146, 1940. 19. A]tschu], t~.: Cerebral E n d a r t e r i t i s in an I n f a n t , J. Neuropath. & Expcr. Neurol., April, 1949. 20. Angevine, D. M.: Pathologic A n a t o m y of the Hypophysis and Adrenals in Anencephaly~ Arch. Path. 26: 507, 1938.