Acta neuropath. (Berl.) 32, 245--255 (1975) 9 by Springer-Verlag 1975
Occipital Encephalocele A Pathologic and Anatomic Analysis * V. S. Caviness, J r . a n d P. E v r a r d Eunice Kennedy Shriver Center for lVlental Retardation, Inc., At The Walter E. Fernald State School, Departments of Neurology and Neuropathology of the Massachusetts General Hospital and Harvard Medical School, Boston Massachusetts l~eceived March 10, 1975; Accepted April 8, 1975 Abstract. The brain from an infant with a cystic occipital mass present at birth is examined in serial section. The occipital mass proved to be a rhombie roof ventriculoeele. Within the posterior fossa, it was bound to an occipital lobe eneephaloeele which issued as a diverticulum of the left lateral ventricle through a microgyrie cortical defect in the territory of the left posterior cerebral artery. The posterior medial aspects of both cerebral hemispheres were herniated downward into the widened tentorial gap. Craniolacunaewere prominent on the inner aspect of the skull. The aqueduct and central canal of the spinal cord were widely dilated, although the lateral ventricles were collapsed. I t is suggested that hydrocephalus secondary to obstruction to flow of CSF through the rhombic roof entrained a sequence of events giving rise to the rhombic roof ventrieuloeele and causing occlusion of the posterior cerebral artery and subsequent diverticulation of the lateral ventricle through an infarcted region of the posteriormedial hemisphere.
Iiey words: Eneephalocele, Occipital -- Diverticulum -- Hydrocephalus -- Ventrieulocele. E n c e p h a l o c e l e s are a m o n g t h e r e l a t i v e l y c o m m o n d e v e l o p m e n t a l m a l f o r m a t i o n s of t h e c e n t r a l n e r v o u s s y s t e m e n c o u n t e r e d in e v e r y 3000 t o 10000 live b i r t h s (Lorber, 1967). As m a n y as 80--900/0 of t h e s e occur in t h e occipital r e g i o n (Mealey, 1970). The occipital eneephaloeele is p a r t i c u l a r l y well k n o w n to tile n e n r o s u r g e o n who m a y be called u p o n to excise t h e sac, r e p a i r t h e defect or c o n t r o l t h e a s s o c i a t e d h y d r o c e p h a l u s which m a y be severe e n o u g h to cause a n a b n o r m a l l y r a p i d increase in h e a d circumference in m o r e t h a n 500/0 of eases ( B r a n d e s k y a n d Klick, 1969; K l i e k a n d B r a n d e s k y , 1969). P a r a d o x i c a l l y , t h e m o r b i d a n a t o m y of this c o m m o n , clinically i m p o r t a n t m a l f o r m a t i o n has b e e n r e l a t i v e l y n e g l e c t e d b y pathologists, a n d no c o h e r e n t view o f its p a t h o g e n e s i s has e m e r g e d from existing studies ( K a r c h a n d Urich, 1972). The p r e s e n t s t u d y is a ease analysis in whole b r a i n serial section of a n occipital lobe eneephalocele a s s o c i a t e d w i t h a r h o m b i e r o o f ventrienlocele. Cytoarehiteet o n i c a n d t o p o g r a p h i c evidence suggests a plausible m e c h a n i s m of p a t h o g e n e s i s for t h e e n e e p h a l o e e l e in t h i s a n d s i m i l a r eases. * This investigation was supported in part by Public Health Service International Postdoctoral Research Fellowship I FO 5 TW 0178301 and by NICHD grant l i D 04147 from NIIt. Dr. Caviness is a Research Scholar of the Joseph P. Kennedy, Jr., Memorial Foundation.
246
V.S. Caviness, Jr., and P. Evrard
Materials and Methods The brain and a segment of the cervical spinal cord were fixed in 10~ formalin, embedded in celloidin and sectioned serially in the sagittal plane at 35 microns (Yakovlev, 1970). Every 10th section was stained by the lqissl method and the adjacent section by the Loyez method. Every 100th section was stained with hematoxylin-eosin.
Case History This female infant was delivered without complication at term to a 26 year old para II, gravida I I woman in good health. The pregnancy had been uneventful, and there was no family history of neurologic disease. A cystic, 7 • 6 cm mass was evident in the occipital region of the infant at birth. Head circumference was 29.5 cm. The fontanels were flat; the anterior measured 1.5 • 1.5 cm, the posterior, 1 • 1 cm. There was no overt spina bifida. Details of neurological examination in the perinatal period are not known. Suckling was poor. Naso-gastric tube feeding was complicated by regurgitation and aspiration, and death occurred with cardio-respiratory arrest on the fourth postnatal day.
General Autopsy The body weighed 2640g. The eyes, ears, nose, nasal mucosa, torso and extremities were normal. Carotid and vertebral ar~ries and their principal intraeranial branches were of
normal distribution and were patent. Except for bronchopneumonia, the thoracic, abdomina~ and pelvic viscera were normal.
Pathologic and Anatomic Analysis o] the Central Nervous System The thickness of the skull was reduced, and cranial lacunae were prominent on the inner surface. The occipital mass passed through a defect in the occipital squama located to the left of midline. Extracranially it was covered by dense integument. Intracranially it was bound by dense, fibrous adhesions to the meninges of the posterior fossa and brain stem. The cyst proved to be an expansion of the roofing membrane of the fourth ventricle, and its attachment along the margin of the ventricle was readily identified. The foramina of Luschka and Magendie could not be identified by either gross or histologic examination. The rhombic ventriculocele was bound, rostrally, by dense adhesions to a second, smaller, cystic mass which proved to be an encephalocele emanating from the occipital lobe of the left cerebral hemisphere. The cavity of the second cyst was continuous, through a pedicle, with the medial aspect of the lateral ventricle at a point just caudal to the trigone (Fig. 1). The temporal lobes were herniated bilaterally into the tentorial gap where they were closely apposed to t h e mid-brain. The tentorium, which was reduced to a narrow sickle-shaped margin, was attached far caudally so that the posterior cranial fossa was abnormally small. Despite this deformation the vein of Galen, the internal cerebral vein and the lateral sinuses could be identified in their normal relative positions. The cortex of the cerebral hemispheres was normal, with the exception of bilateral anomalies in the medial and lateral oecipito-temporal and parahippocampal gyri (Fig. 2). The area of cortical abnormality on the left was more complex and more extensive. The pedicle of the encephalocele lay ventromedially at the interface of abnormal and normal cortex (Fig. 1). Its lateral aspect was formed of gliotic central white matter from which the overlying cortex was effaced. Distally neuroglial fragments were scattered through the dense fibrous tissue of the encephaloeele. The remainder of the cortical abnormality on the left as well as that on the right was of the classic, 4-layered microgyrie, cytoarchitectonic type (l~ichman et al., 1973, 1974). The cellsparse microgyric layer I I I abutted npon the mid-cortical layers of adjacent normal cortex. Further, the cellular microgyric layers I I and IV were continuous with, and cytologically identical to, the outer and inner layers respectively of adjacent normal cortex. A full thickness mural, or poreneephalic, defect lay at the posterior margin of the cortical abnormality on the left. As is frequently the case with porencephalic defects, cortex with classic, 4-layered microgyric, cytoarchitectonic pattern (Fig. 1Aand3) continued inward from the convexity to line the
Occipital Encephalocele
247
walls of the porus as well as the subjacent region of the lateral ventricle (Levine et al., 1974). Within the porencephalic defect neuronal layers of infolded cortex were usually attenuated and, in places, completely effaced. However, even near the ventricle segments of cortex with typical microgyrie features could be recognized in favorable sections (Figs. 1A and 3). In such segments the radial pattern of neuronal alignment was preserved. The morphology of the deep
Fig. 1[A. Paramedian sagittal section through left cerebral hemisphere. Mierogyric cortex (m) is folded inward to line the porus wall and subjacent ventricle. Occipital lobe encephalocele (e) communicates with lateral ventricle through a pediele (arrow). The line of attachment of the rhombic roof ventriculocele (v), removed at autopsy, lies at the margin of the distended fourth ventricle. Cresyl violet • 1,2
B Fig. 1 B. Schematic representation of the brain stem and rhombic roof ventriculocele (v) at a plane medial to the communication between encephalocele and lateral ventricle. The position of the,poreneephalie defect is crosshatched. The third nerve and its radicles issue from the elongated and attenuated meseneephalon
248
V.S. Caviness, Jr., and P. E v r a r d
l Fig. 2. Schematic view of the basal surface of the forebrain. The positions of the larger left and the right cortical defects are stippled
cellular zone was typical of neocortical layer VI, while cells of pyramidal morphology with ascending, dominant, apical dendrite typical of layers I I I and I I lay in a n outer cellular zone. Identical examples of this configuration are illustrated in Levine et al. (1974). Typically, the cortical surfaces on opposite lips of the defect were apposed a n d fused along a dense glialmesenchymal seam. Particularly at the ventricular level the infolded cortex was contorted so t h a t in individual sections segments appeared isolated from the cortical continuum. Continuity could be reconstructed from the sequence of serial sections, however, establishing t h a t there were no "heterotopias" associated with the malformation. The central nuclear structures a n d fiber tracts of the forebrain were unremarkable except for the mammillary complex where there was indistinct differentiation into the medial a n d lateral subnuclei. The subthalamic region and brain stem were elongated and attenuated. Although the collieuiar plate was flattened, the normal cellular a n d fiber p a t t e r n s were preserved. No cells of the red nucleus nor fibers of the dentato-rubral or dento-thalamie tracts could be identified in the mesencephalic tegmentum. The rhombencephalon lay fully within the small posterior fossa. The pons and medulla were angulated sharply upward along the line of exit of the rhombic roof ventriculocele (Fig. 1). Gliotic stumps of the eerebellar peduncles passed from the b r a i n stem into the fibrotie base of the overlying cystic mass. Only neuroglial fragments marked the former location of the entrapped cerebellum. All cranial nerves of the brain stem a n d their nuclei, with the exception of the fourth, were present in normal relative positions. A few cells of the griseum pontis b u t no neurons of the inferior olivary complex nor fibers of the amieulum could be identified. By contrast, the locus coeruleus was richly cellular. The position of the cord in the vertebral canal, a n d the course of the spinal roots were normal. There was no meningomyelocele. The gray columns and fiber tracts appeared normal, with the exception t h a t the spino-cerebellar t r a c t could not be identified with confidence. Clarke's column was not included in the available sections. The lateral ventricles were collapsed. The foramina of Monro aqueduct, and fourth ventricle were widely dilated, a n d a widely p a t e n t hydromyelic cavity was continuous with the fourth ventricle. The neuroglial roof of the cavity was everywhere i n t a c t (Fig.4). Throughout the ventricular system, b u t particularly in t h e aqueduct, fourth ventricle and hydromyelic cavity there were m a n y gaps in the epcndymal lining, the ependymal cells were flattened a n d sub-
Occipital Enceph~locele
249
Fig. 3. Mierogyric cortex in the depths of the porus near tip of pointer in Fig. 1A. A few pyramidal cells (arrow) typical of layer V of normal cortex survive around a capillary in the mideortical, microgyric layer III. Cresyl violet • 97.5
ependymal gliosis was intense. No ependyma was present in the region of the porencephalic defect. The choroid plexuses were fibrotic. The cells were atrophic and contained much hemosiderin pigment.
Discnssion A v a r i e t y of pathologic findings in the present case are consistently associated with congenital hydrocephalus of a d v a n c e d degree: occipital lobe eneephalocele (Monakow, 1899), rhombic ventriculocele (Brodal, 1945; Brodal and HouglieHanssen, 1959), wide communication of the central canal of the spinal cord and the fourth ventricle (Gardner, 1973; McKenzie and Emery, 1971; E m e r y and Mac
250
V. S. Caviness, Jr., and P. Evrard
Fig. 4. Transverse section through upper cervical cord. Scattered islands of ependymal cells persist at the border of the hydromyelic cavity. Cresyl violet • ]0
Kenzie, 1973), general dilatation of the spinal central canal, fourth ventricle, aqueduct, and foramina of Monro with widespread loss of ependymal cells and dense subependymal gliosis (lgussell, 1949; Bering and Sato, 1963; Weller and Wi~nicwski, 1969; Lorenzo st al., 1970), and thinning of the skull with craniolacunae (Ingraham and Scott, 1943; Cameron, 1957). Small head circumference, such as found in the present ease, is paradoxically common when congenital hydroecpha]us is associated with encepha]ocele or meningomyeloeele (Cameron, 1957; O'Neill, 1961). This cannot be attributed simply to reduced bulk of cerebrum or cerebellum, because head circumference may increase at a dramatic, abnormal rate consequent to surgical ablation of the cyst (Penfield and Cone, 1932 ; Laurence, 1958; Williams, 1973 ; Wealthall, 1973). Apparently cranial expansion is prevented by the cyst despite active hydrocephalus. Such cysts are in continuity with the ventrieular system (Monakow, 1899; Russell, 1949; Wealthall, 1973). Because they are not constrained by bony encasement, their resistence to expansion is evidently low, and expansion occurs preferentially in the cyst in response to hydrocephMie force. Similarly, a single cerebral hemisphere will expand in the region of restricted eraniectomy in hydroeephalie experimental animals (I{oehwald et al., 1972).
Occipital Encephaloceie
251
Collapse of the lateral ventricles observed in the present and other examples of occipital lobe encephaloceles in humans (Karch and Urich, 1972) is not an argumerit against hydrocephalus; it also occurs in hydrocephalic experimental animals after surgical ablation of the ehoroid plexuses of the forebrain ventricular system (Dandy and Blackfan, 19i7; Hammock and Milhorat, 1973). The collapse appears to come about as a consequence of scarring and traction along the surgical approach route in experimental animals (Hammock and Milhorat, 1973). A severe degree of traction appears to have been exerted along the cerebral peduncles, the subthalamic region and the brainstem which were attenuated and drawn down into the posterior fossa, and the brainstem was buckled upward along the line of exit of the rhombic ventriculoeele. As may be observed in experimental animals, such traction could have led to collapse of the lateral ventricles despite hydrocephalus (Hammock and Milhorat, 1973). Rhombie roof ventriculoceles expanding superiorly from the fourth ventricle as in the present case, are typically associated with the Dandy-Walker malformation of the midline cerebellum (Dandy and Blackfan, 1917 ; Taggert and Walker, 1942 ; Brodal, 1945 ; Brodal and Houglie-Hanssen, 1959). A malformation identical to the Dandy-WMker malformation in humans occurs in the hydrocephalic mouse, hy-1 (Bonnevie, 1943; Brodal et al., 1944; Brodal, 1945; Bonnevie and Brodal, 1946). In this mutant the ventriculocele which occurs as a consequence of obstruction to outflow of CSF through the roof of the fourth ventricle, causes damage to the cerebellum by direet compression as it expands. It is a reasonable inference from this animal model that rhombie ventrieuloceles encountered in human developmental pathology, the present specimen included, arise by a similar hydrocephalic mechanism (Brodal, 1945; Brodal and tIouglie-Hanssen, 1959; Evrard and Caviness, 1974). The small pyramidal neurons of layer II, the last of the neocortical neurons to complete their migrations, are in normal relative position in the microgyrie cortex. This observation requires that the microgyric cortical defects in this case was produced by an insult occurring after migration to the cortex was complete, yet before the definitive pattern of tertiary convolution was established, i.e., between the 6th and 7th fetal months (Richman et al., 1973, 1974). This inference from anatomy is supported by the correlative clinical, pathologic studies of microgyria of Hallervorden (1949) and of Bankl and Jellinger (1967). The acellular microgyric layer I I I is reminiscent of the effect of ischemie laminar necrosis (t~iehman et al., 1973, 1974; Levine et al., 1974). The posterior medial regions of both cerebral hemispheres of the present ease were driven downward into the tentorial gap and engaged by the tentorium. This may have occurred consequent to hydroeephMic force acting supratentorially as well as to traction exerted on the brainstem from below by the expanding rhombie ventrieulocele. Had the posterior cerebral arteries been critically occluded by entrapment against the tentorium, bilateral cerebral infarctions would have been expected in the territory of the cortical defects encountered in the present ease (e. g., see Fig. 84A, Escourolle and Poirier, 1971). The occipital lobe encephalocele is a diverticulum of the lateral ventricle which extrudes through the left, more severe, cortical defect. Diverticula which are identical with respect to the point of egress from the ventricle, trajectory through
252
V.S. Caviness, Jr., and P. Evrard
the tentorial notch into the posterior fosse and tendency to impinge upon the cerebellum may come about as a consequence of severe hydrocephalus acquired in postnatal life (Sweet, 1940; Childe and McNaughton, 1942; Pennybacker and Russell, 1943; Russell, 1949). Similar diverticula of the occipital horns of the lateral ventricle also arise as a relatively late complication of hydrocephalus induced in experimental animals by ~ variety of teratogenes (Carton st el., i961; Duekett, 1972). I t is thus plausible that the occipital lobe eneephalocele in the present case came about as a consequence of hydrocephalic force, with the point of extrusion determined by a defect in the cerebral wall caused by infarction. Fragments of cerebellar tissue were scattered through the area of interface between the ventriculoeele and encephalocele, and the truncated peduncles were of substantial proportion. Presumably the developing cerebellum was destroyed by entrapment between the 2 cysts during the period of rapid tissue growth in the early third trimester. The degeneration of collateral cerebellar nuclei in the brain stem is reasonably considered secondary to loss of the connections with the cerebellum (Harkmark, 1956; Evrard and Caviness, 1974). The association of rhombic roof ventriculocele, occipital encephalocele extending into the posterior fosse and damage to the entrapped cerebellum is not unusual (Cleland, 1882 ; Monakow, 1899; Karch and Urich, 1972). The character of cerebral cortex at the base of the occipital lobe encephaloceles has, in general, not been described, although mierogyria has been specifically mentioned in single cases reported by Shryok and Knighton (1940), Karch and Urieh (1972), and Engel and Buehan (1974). Transtentoria] herniation of the medial aspect of the cerebral hemispheres with critical occlusion of the posterior cerebral artery, infarction of the inferior and medial region of the cerebral hemispheres and hydrocephalic extrusion of a ventricular diverticulum through the mural defect may be a general pathogenic sequence for all such cases. Occipital Iobe eneeplla~oceles, like spinal meningomyeloeeIes, are occasionally associated with variants of the Chiari deformity (Chiari, 1895), and two views, still hypothetical, to explain the pathogenesis of meningomyelocele have been advanced to explain the origins of the encephaloceles as well. The first, originally proposed by yon 1%ecklinghausen (1886), holds that a mesenchymal defect of undetermined origin is primary and that neural tissue expands secondarily through the resulting bony defect. Even before the end of the last century this theory was considered untenable by both experimental embryologists and developmental pathologists, because of the relatively greater precocity of development of neural with respect to mesenchymal tissues (reviewed by Monakow, 1899). Subsequent studies of normal developmental sequence (Streeter, 1915) as well as experimental studies (Holtzer, 1952, 1968; Holtzer and Detwiler, 1953; Holtfreter, 1968) contribute additional evidence that neural tissue determines cellular differentiation, augments growth and confers form upon adjacent mesenchymal tissues rather than the reverse. Bony defects like that in the present case come about, presumably, as a consequence of focally directed pressure leading to bony erosion, as is known to occur in postnatal life (gupe, 1938). In general, such bony defects occur in or near the occipital fissure where bony union is delayed, presumably a point of relative weakness during early development (O'lgahiIley, 1952).
Occipit~al Encephalocele
253
The second t h e o r y holds t h a t occipital lobe encephaloceles come a b o u t as a consequence of failure of closure of the n e u r a l t u b e (Campbell, 1948). W h a t e v e r the role of such a n e v e n t i n the d e v e l o p m e n t of spinal defects, it could n o t be the morphogenetic m e c h a n i s m of the encephaloceles e n c o u n t e r e d in the p r e s e n t a n d similar specimens because the position of the defect i n no sense corresponds to the closure line of the n e u r a l t u b e (Karch a n d Urich, 1972).
References Bankl, H., Je[linger, K. : ZcntralnervSse Sch~den nach fetaler Kohlenoxydvergiftung. Beitr. path. Anat. 135, 350--376 (1967) Bering, E. A., Jr., Sato, 0.: Hydroce, ph~us: changes in formation and absorption of cerebro~ spinal fluid within the cerebral ventricles. J. Neurosurg. 20, 1050--1063 (1963) Bonnevie, K. : Hereditary hydrocephalus in the house mouse. I. Manifestations of the bymutation after birth and in embryos 12 days old or more. Skr. norske Vidensk.-Akad., I. Mat.-nat. K1.4, 1--32 (1943) Bonnevie, K., Brodal, A. : Hereditary hydrocephalus m the house mouse. IV. The development of the cerebellar anomalies during fetal life with notes on the normal development of the mouse cerebellum. Skr. norske Vidensk.-Akad., I. Mat.-nat. K1.4, 1--60 (1946) Brandesky, G. yon, Klick, A. : Encephalocele und hydrocephalus. Z. Kinderchir. 7, 583--589 (1969) Brodal, A. : Defective development of the cerebellar vermis (partial agenesis) in ~ child. Skr, norske Vidensk.-Akad., I. Mat.-nat. K1.3, 1--40 (1945) Brodal, A., Bonnevie, K., Harkmark, W. : Hereditary hydrocephalus in the house mouse. I[. The anomalies of the cerebellum: partial defective development of the vermis. Skr. norske Vidensk.-Akad, I. Mat.- nat. K1. S, 1 --42 (1944) Brodal, A., l-Iouglie-FIanssen, E. : Congenital hydrocephalus with defective development of the cerebellar vermis (Dandy-Walker syndrome): Clinical and anatomical findings in two cases with particular reference to the so-called atresia of the foramina of Magendie and Luschka. J. Neurol. Neurosurg. Psychiat. 22, 99--108 (1959) Cameron, A. H.: The Arnold-Chiari and other neuro-anatomical malformations associated with spina bifida. J. Path. Bact. 78, 195--212 (1957) Campbell, J. B. : Congenital anomalies of the neural axis. Amcr. J. Surg. 7~, 231--256 (1948) Carton, C. A., Pascal, R. R., Tennyson, V. M. : Hydrocephalus and vitamin A deficiency in the rabbit: general considerations. In: Disorders of the Developing Nervous System. W. S. Fields and M. M. Desmond (eds.), pp. 214--266, Springfield, Ill.: Ch. C. Thomas 196i Chiari, H. : Uber die Vergndcrungen des Kleinhirns, der Pons und der Medulla oblongata in Folge yon congenitaler Hydrocephalie des GroShirns. Denkschr. Akad. Wissensch,-naturw. K1.63, 71--116 (1895) Chitde, A. E., McNaughton, F. L. : Diverticula of the Ia~era[ ventricles extending into the cerebeIlar fossa. Arch. Neurol. Psychiat. (Chic.) 47, 768--778 (1942) Cleland, J. : Contribution to the study of spina bifida, encephalocele, and anencephalus. J. Anat. Physiol. 17, 257--292 (1882) Dandy, W. E., Blackfan, K. D.: Internal hydrocephalus. Amer. J. Dis. Child. 14, 424--443 (1917) Duckett, S.: Teratogenesis caused by tellurium. Ann. N.Y. Acad. Sci. 192, 220--226 (1972) Emery, J. L., McKenzie, ~N.: Medullo-cervical dislocation deformity (Chiari II deformity) related to neurospinal dysraphism (meningomyelocele). Brain 96, 155--162 (1973) Engel, R., Buchan, G. C. : Occipital enccphaloceles with and without visual evoked potentials. Arch. Neurol. (Chic.) 30, 314--318 (1974) Escourolle, R., Poirier, J. : Manuel E16mentaire de 57europathologie. Paris: M~sson and Cie 1971 Evrard, P., Caviness, V. S., Jr. : Extensive developmental defect of the cerebellum associated with posterior fossa ven~riculocele. J. Neuropath. exp. Neurol. 88, 385--399 (1974) Gardner, W. J. : The Dysraphic Sta,tes. Amsterdam: Exeerpta Medica 1973
254
V. S. Caviness, Jr., and P. Evrard
Hallervorden, J. : t3ber eine Kohlenoxydvergiftung im Fetalleben mit EntwieklungsstSrung der ttirnrinde. Allg. Z. Psychiat. 124, 289--298 (1949) Hammock, M. K., Milhorat, T. H.: Recent studies on the formation of cerebrospinal fluid. Develop. reed. Child Neurol. (Suppl.) 29, 27--34 (1973) Harkmark, W. : The influence of the cerebellum on development and maintenance of the inferior olive and the pons. An experimental investigation on chick embryos. J. exp. Zool. 181, 333--371 (1956) Hochwald, G. M., Epstein, F., ~alhan, C., Ransohoff, J. : The rble of the skull and dura in experimental feline hydrocephalus. Develop. reed. Child Neurol. (Suppl.) 27, 65--69 (1972) Holtfreter, J.: Mesenchyme and epithelia in inductive and morphogenetie processes. In: Epithelial-Mesenchymal Interactions, R. Fleischmajer and R. E. Billingham (eds.), pp. 1--30. Baltimore: Williams and Wilkins 1968 ttoltzer, H. : An experimental analysis of the development of the spinal column. Part I. Response of pre-cartilage cells to size variations of the spinal cord. J. exp. Zool. 121, 121--147 (1952) Holtzer, H. : Induction of chondrogenesis: A concept in quest of mechanisms. In: EpithelialMesenchymal Interactions. R. Fleischmajer and R. E. Billingham (eds.), pp. 152--164. Baltimore: Williams and Wilkins 1968 Holtzer, H., Detwiler, S. 1~.: An experimental analysis of the development of the spinal column J. exp. Zool. 128, 335--369 (1953) Ingraham, F. D., Scott, H.W.,Jr. : Spina bifida and cranium bifidum. Hew. Engl. J. Med. 229, 108--114 (1943) Jupe, M. H. : The reaction of the bones of the skull to intraeranial lesions. Brit. J. Radiol. 11, 146--164 (1938) Karch, S. B., Urich, H. : Occipital encephalocele: A morphological study. J. neurol. Sei. 15, 89--112 (1972) Klick, A., Brandesky, G. : Durch eine 5~embrana interventricularis bedingter Hydrocephalus mit Encephalocele. Zbl. allg. Path. path. Anat. 112, 584--589 (1969) Laurence, K. M. : The natural history of hydrocephalus. Lancet 1958 iI, 1152--1154 Levine, D. N., Fisher, M. A., Caviness, V. S. Jr. : Porencephaly with mierogyria: A pathologic study. Aeta neuropath. (Ber].) 29, 99 113 (1974) Lorber, J. : The prognosis of occipital encephalocele. Develop. med. Child Neurol. (Suppl.) 13, 75--86 (1967) Lorenzo, A. V., Page, L. K., Watters, G. V.: Relationship between eerebrospinal fluid formation, absorption and pressure in human hydrocephalus. Brain 98, 679--692 (1970) MacKenzie, N. G., Emery, J. L. : Deformities of the cervical cord in children with neurospinal dysraphism. Develop. reed. Child Neurol. (Suppl.) 25, 58--67 (1971) Mealey, J., Jr., Dzenitis, A. J., Hockey, A. A. : The prognosis of encephaloceles. J. Neurosurg. 82, 209--218 (1970) Monakow, C. yon: (~ber die MiBbildungen des Zcntralnervensystems. Ergeb. allg. Path. path. Anat. 6, 513--582 (1899) O'Neill, E. M. : Normal head growth and the prediction of head size in infantile hydrocephalus. Arch. Dis. Child. 86, 241--252 (1961) O'Rahilly, R. : Anomalous occipital apertures. Arch. Path. 58, 509--519 (1952) Penfield, W., Cone, W. : Spina bi/ida and cranium bi/idum. J. Amer. reed. Ass. 98, 454--461 (1932) Pennybacker, J., Russell, D. S.: Spontaneous ventricular rupture in hydrocephalus, with subtentorial cyst formation. J. Neurol. Psychiat. 6, 38--45 (1943) Recklinghausen, F. yon: Untersuchungen fiber die Spina bi/ida. Virchows Arch. path. Anat. 105, 243--330, 371--455 (1886) Richman, D. P., Stewart, R. M., Caviness, V.S.,Jr.: Microgyria, lissencephaly, and neuron migration to the cerebral cortex: An architectonic approach. Neurology (Minneap.) 28, 413 (1973) Richman, D. P., Stewart, R. M., Caviness, V. S., Jr. : Cerebral microgyria in a 27 week fetus: An architectonic and topographic analysis. J. Neuropath. exp. Neurol. 88, 374--384 (1974) Russell, D. S. : Observations on the Pathology of Hydrocephalus. MRC Publication No. 265. London: HMSO 1949
Occipital Eneephalocele
255
Shryock, H., Knighton, 1%.S.: Arhinencephaly with associated agenesis of the corpus callosum and other anomalies. Bull. Los Angeles neurol. Soc. 5, 192--201 (1940) Streeter, G. L. : The development of venous sinuses of the dura mater in the hmnan embryo. Amer. J. Anat. 18, 145--178 (1915) Sweet, W. H.: Spontaneous cerebral ventriculostium. Arch. Neurol. Psychiat. (Chic.) 44, 532--540 (1940) Taggert, J. K., Walker, A. E. : Congenital atresia of the foramens of Luschka and Magendie. Arch. Neurol. Psychiat. (Chic.) 48, 583--612 (1942) Wealthall, S. R. : An investigation of the factors involved in regulating ventricular size and the production of hydrocephalus. Develop. reed. Child Neurol. (Suppl.) 29, 1--11 (1973) Weller, R. O., Wigniewski, H.: Histological and ultrastructural changes with experimental hydrocephalus in adult rabbits. Brain 92, 819--828 (1969) Williams, B. : Is aqucductal stenosis a result of hydrocephalus? Brain 96, 399--412 (1973) Yakovlev, P. I. : Whole brain serial histological sections. In: Neuropathology: 1YIethods and Diagnosis, W. Tedesehi (ed.), pp. 371--378. Boston: Little Brown & Co. 1970 Dr. Verne S. Caviness, Jr. Eunice Kennedy Shriver Center for Mental l~etardation Inc. At the Walter E. Fernald State School 200 Trapelo Road Waltham, Massachusetts 02154 U.S.A.
18 Actaneuropath.(Berl.):Bd.32
Occipital Encephalocele A Pathologic and Anatomic Analysis * V. S. Caviness, J r . a n d P. E v r a r d Eunice Kennedy Shriver Center for lVlental Retardation, Inc., At The Walter E. Fernald State School, Departments of Neurology and Neuropathology of the Massachusetts General Hospital and Harvard Medical School, Boston Massachusetts l~eceived March 10, 1975; Accepted April 8, 1975 Abstract. The brain from an infant with a cystic occipital mass present at birth is examined in serial section. The occipital mass proved to be a rhombie roof ventriculoeele. Within the posterior fossa, it was bound to an occipital lobe eneephaloeele which issued as a diverticulum of the left lateral ventricle through a microgyrie cortical defect in the territory of the left posterior cerebral artery. The posterior medial aspects of both cerebral hemispheres were herniated downward into the widened tentorial gap. Craniolacunaewere prominent on the inner aspect of the skull. The aqueduct and central canal of the spinal cord were widely dilated, although the lateral ventricles were collapsed. I t is suggested that hydrocephalus secondary to obstruction to flow of CSF through the rhombic roof entrained a sequence of events giving rise to the rhombic roof ventrieuloeele and causing occlusion of the posterior cerebral artery and subsequent diverticulation of the lateral ventricle through an infarcted region of the posteriormedial hemisphere.
Iiey words: Eneephalocele, Occipital -- Diverticulum -- Hydrocephalus -- Ventrieulocele. E n c e p h a l o c e l e s are a m o n g t h e r e l a t i v e l y c o m m o n d e v e l o p m e n t a l m a l f o r m a t i o n s of t h e c e n t r a l n e r v o u s s y s t e m e n c o u n t e r e d in e v e r y 3000 t o 10000 live b i r t h s (Lorber, 1967). As m a n y as 80--900/0 of t h e s e occur in t h e occipital r e g i o n (Mealey, 1970). The occipital eneephaloeele is p a r t i c u l a r l y well k n o w n to tile n e n r o s u r g e o n who m a y be called u p o n to excise t h e sac, r e p a i r t h e defect or c o n t r o l t h e a s s o c i a t e d h y d r o c e p h a l u s which m a y be severe e n o u g h to cause a n a b n o r m a l l y r a p i d increase in h e a d circumference in m o r e t h a n 500/0 of eases ( B r a n d e s k y a n d Klick, 1969; K l i e k a n d B r a n d e s k y , 1969). P a r a d o x i c a l l y , t h e m o r b i d a n a t o m y of this c o m m o n , clinically i m p o r t a n t m a l f o r m a t i o n has b e e n r e l a t i v e l y n e g l e c t e d b y pathologists, a n d no c o h e r e n t view o f its p a t h o g e n e s i s has e m e r g e d from existing studies ( K a r c h a n d Urich, 1972). The p r e s e n t s t u d y is a ease analysis in whole b r a i n serial section of a n occipital lobe eneephalocele a s s o c i a t e d w i t h a r h o m b i e r o o f ventrienlocele. Cytoarehiteet o n i c a n d t o p o g r a p h i c evidence suggests a plausible m e c h a n i s m of p a t h o g e n e s i s for t h e e n e e p h a l o e e l e in t h i s a n d s i m i l a r eases. * This investigation was supported in part by Public Health Service International Postdoctoral Research Fellowship I FO 5 TW 0178301 and by NICHD grant l i D 04147 from NIIt. Dr. Caviness is a Research Scholar of the Joseph P. Kennedy, Jr., Memorial Foundation.
246
V.S. Caviness, Jr., and P. Evrard
Materials and Methods The brain and a segment of the cervical spinal cord were fixed in 10~ formalin, embedded in celloidin and sectioned serially in the sagittal plane at 35 microns (Yakovlev, 1970). Every 10th section was stained by the lqissl method and the adjacent section by the Loyez method. Every 100th section was stained with hematoxylin-eosin.
Case History This female infant was delivered without complication at term to a 26 year old para II, gravida I I woman in good health. The pregnancy had been uneventful, and there was no family history of neurologic disease. A cystic, 7 • 6 cm mass was evident in the occipital region of the infant at birth. Head circumference was 29.5 cm. The fontanels were flat; the anterior measured 1.5 • 1.5 cm, the posterior, 1 • 1 cm. There was no overt spina bifida. Details of neurological examination in the perinatal period are not known. Suckling was poor. Naso-gastric tube feeding was complicated by regurgitation and aspiration, and death occurred with cardio-respiratory arrest on the fourth postnatal day.
General Autopsy The body weighed 2640g. The eyes, ears, nose, nasal mucosa, torso and extremities were normal. Carotid and vertebral ar~ries and their principal intraeranial branches were of
normal distribution and were patent. Except for bronchopneumonia, the thoracic, abdomina~ and pelvic viscera were normal.
Pathologic and Anatomic Analysis o] the Central Nervous System The thickness of the skull was reduced, and cranial lacunae were prominent on the inner surface. The occipital mass passed through a defect in the occipital squama located to the left of midline. Extracranially it was covered by dense integument. Intracranially it was bound by dense, fibrous adhesions to the meninges of the posterior fossa and brain stem. The cyst proved to be an expansion of the roofing membrane of the fourth ventricle, and its attachment along the margin of the ventricle was readily identified. The foramina of Luschka and Magendie could not be identified by either gross or histologic examination. The rhombic ventriculocele was bound, rostrally, by dense adhesions to a second, smaller, cystic mass which proved to be an encephalocele emanating from the occipital lobe of the left cerebral hemisphere. The cavity of the second cyst was continuous, through a pedicle, with the medial aspect of the lateral ventricle at a point just caudal to the trigone (Fig. 1). The temporal lobes were herniated bilaterally into the tentorial gap where they were closely apposed to t h e mid-brain. The tentorium, which was reduced to a narrow sickle-shaped margin, was attached far caudally so that the posterior cranial fossa was abnormally small. Despite this deformation the vein of Galen, the internal cerebral vein and the lateral sinuses could be identified in their normal relative positions. The cortex of the cerebral hemispheres was normal, with the exception of bilateral anomalies in the medial and lateral oecipito-temporal and parahippocampal gyri (Fig. 2). The area of cortical abnormality on the left was more complex and more extensive. The pedicle of the encephalocele lay ventromedially at the interface of abnormal and normal cortex (Fig. 1). Its lateral aspect was formed of gliotic central white matter from which the overlying cortex was effaced. Distally neuroglial fragments were scattered through the dense fibrous tissue of the encephaloeele. The remainder of the cortical abnormality on the left as well as that on the right was of the classic, 4-layered microgyrie, cytoarchitectonic type (l~ichman et al., 1973, 1974). The cellsparse microgyric layer I I I abutted npon the mid-cortical layers of adjacent normal cortex. Further, the cellular microgyric layers I I and IV were continuous with, and cytologically identical to, the outer and inner layers respectively of adjacent normal cortex. A full thickness mural, or poreneephalic, defect lay at the posterior margin of the cortical abnormality on the left. As is frequently the case with porencephalic defects, cortex with classic, 4-layered microgyric, cytoarchitectonic pattern (Fig. 1Aand3) continued inward from the convexity to line the
Occipital Encephalocele
247
walls of the porus as well as the subjacent region of the lateral ventricle (Levine et al., 1974). Within the porencephalic defect neuronal layers of infolded cortex were usually attenuated and, in places, completely effaced. However, even near the ventricle segments of cortex with typical microgyrie features could be recognized in favorable sections (Figs. 1A and 3). In such segments the radial pattern of neuronal alignment was preserved. The morphology of the deep
Fig. 1[A. Paramedian sagittal section through left cerebral hemisphere. Mierogyric cortex (m) is folded inward to line the porus wall and subjacent ventricle. Occipital lobe encephalocele (e) communicates with lateral ventricle through a pediele (arrow). The line of attachment of the rhombic roof ventriculocele (v), removed at autopsy, lies at the margin of the distended fourth ventricle. Cresyl violet • 1,2
B Fig. 1 B. Schematic representation of the brain stem and rhombic roof ventriculocele (v) at a plane medial to the communication between encephalocele and lateral ventricle. The position of the,poreneephalie defect is crosshatched. The third nerve and its radicles issue from the elongated and attenuated meseneephalon
248
V.S. Caviness, Jr., and P. E v r a r d
l Fig. 2. Schematic view of the basal surface of the forebrain. The positions of the larger left and the right cortical defects are stippled
cellular zone was typical of neocortical layer VI, while cells of pyramidal morphology with ascending, dominant, apical dendrite typical of layers I I I and I I lay in a n outer cellular zone. Identical examples of this configuration are illustrated in Levine et al. (1974). Typically, the cortical surfaces on opposite lips of the defect were apposed a n d fused along a dense glialmesenchymal seam. Particularly at the ventricular level the infolded cortex was contorted so t h a t in individual sections segments appeared isolated from the cortical continuum. Continuity could be reconstructed from the sequence of serial sections, however, establishing t h a t there were no "heterotopias" associated with the malformation. The central nuclear structures a n d fiber tracts of the forebrain were unremarkable except for the mammillary complex where there was indistinct differentiation into the medial a n d lateral subnuclei. The subthalamic region and brain stem were elongated and attenuated. Although the collieuiar plate was flattened, the normal cellular a n d fiber p a t t e r n s were preserved. No cells of the red nucleus nor fibers of the dentato-rubral or dento-thalamie tracts could be identified in the mesencephalic tegmentum. The rhombencephalon lay fully within the small posterior fossa. The pons and medulla were angulated sharply upward along the line of exit of the rhombic roof ventriculocele (Fig. 1). Gliotic stumps of the eerebellar peduncles passed from the b r a i n stem into the fibrotie base of the overlying cystic mass. Only neuroglial fragments marked the former location of the entrapped cerebellum. All cranial nerves of the brain stem a n d their nuclei, with the exception of the fourth, were present in normal relative positions. A few cells of the griseum pontis b u t no neurons of the inferior olivary complex nor fibers of the amieulum could be identified. By contrast, the locus coeruleus was richly cellular. The position of the cord in the vertebral canal, a n d the course of the spinal roots were normal. There was no meningomyelocele. The gray columns and fiber tracts appeared normal, with the exception t h a t the spino-cerebellar t r a c t could not be identified with confidence. Clarke's column was not included in the available sections. The lateral ventricles were collapsed. The foramina of Monro aqueduct, and fourth ventricle were widely dilated, a n d a widely p a t e n t hydromyelic cavity was continuous with the fourth ventricle. The neuroglial roof of the cavity was everywhere i n t a c t (Fig.4). Throughout the ventricular system, b u t particularly in t h e aqueduct, fourth ventricle and hydromyelic cavity there were m a n y gaps in the epcndymal lining, the ependymal cells were flattened a n d sub-
Occipital Enceph~locele
249
Fig. 3. Mierogyric cortex in the depths of the porus near tip of pointer in Fig. 1A. A few pyramidal cells (arrow) typical of layer V of normal cortex survive around a capillary in the mideortical, microgyric layer III. Cresyl violet • 97.5
ependymal gliosis was intense. No ependyma was present in the region of the porencephalic defect. The choroid plexuses were fibrotic. The cells were atrophic and contained much hemosiderin pigment.
Discnssion A v a r i e t y of pathologic findings in the present case are consistently associated with congenital hydrocephalus of a d v a n c e d degree: occipital lobe eneephalocele (Monakow, 1899), rhombic ventriculocele (Brodal, 1945; Brodal and HouglieHanssen, 1959), wide communication of the central canal of the spinal cord and the fourth ventricle (Gardner, 1973; McKenzie and Emery, 1971; E m e r y and Mac
250
V. S. Caviness, Jr., and P. Evrard
Fig. 4. Transverse section through upper cervical cord. Scattered islands of ependymal cells persist at the border of the hydromyelic cavity. Cresyl violet • ]0
Kenzie, 1973), general dilatation of the spinal central canal, fourth ventricle, aqueduct, and foramina of Monro with widespread loss of ependymal cells and dense subependymal gliosis (lgussell, 1949; Bering and Sato, 1963; Weller and Wi~nicwski, 1969; Lorenzo st al., 1970), and thinning of the skull with craniolacunae (Ingraham and Scott, 1943; Cameron, 1957). Small head circumference, such as found in the present ease, is paradoxically common when congenital hydroecpha]us is associated with encepha]ocele or meningomyeloeele (Cameron, 1957; O'Neill, 1961). This cannot be attributed simply to reduced bulk of cerebrum or cerebellum, because head circumference may increase at a dramatic, abnormal rate consequent to surgical ablation of the cyst (Penfield and Cone, 1932 ; Laurence, 1958; Williams, 1973 ; Wealthall, 1973). Apparently cranial expansion is prevented by the cyst despite active hydrocephalus. Such cysts are in continuity with the ventrieular system (Monakow, 1899; Russell, 1949; Wealthall, 1973). Because they are not constrained by bony encasement, their resistence to expansion is evidently low, and expansion occurs preferentially in the cyst in response to hydrocephMie force. Similarly, a single cerebral hemisphere will expand in the region of restricted eraniectomy in hydroeephalie experimental animals (I{oehwald et al., 1972).
Occipital Encephaloceie
251
Collapse of the lateral ventricles observed in the present and other examples of occipital lobe encephaloceles in humans (Karch and Urich, 1972) is not an argumerit against hydrocephalus; it also occurs in hydrocephalic experimental animals after surgical ablation of the ehoroid plexuses of the forebrain ventricular system (Dandy and Blackfan, 19i7; Hammock and Milhorat, 1973). The collapse appears to come about as a consequence of scarring and traction along the surgical approach route in experimental animals (Hammock and Milhorat, 1973). A severe degree of traction appears to have been exerted along the cerebral peduncles, the subthalamic region and the brainstem which were attenuated and drawn down into the posterior fossa, and the brainstem was buckled upward along the line of exit of the rhombic ventriculoeele. As may be observed in experimental animals, such traction could have led to collapse of the lateral ventricles despite hydrocephalus (Hammock and Milhorat, 1973). Rhombie roof ventriculoceles expanding superiorly from the fourth ventricle as in the present case, are typically associated with the Dandy-Walker malformation of the midline cerebellum (Dandy and Blackfan, 1917 ; Taggert and Walker, 1942 ; Brodal, 1945 ; Brodal and Houglie-Hanssen, 1959). A malformation identical to the Dandy-WMker malformation in humans occurs in the hydrocephalic mouse, hy-1 (Bonnevie, 1943; Brodal et al., 1944; Brodal, 1945; Bonnevie and Brodal, 1946). In this mutant the ventriculocele which occurs as a consequence of obstruction to outflow of CSF through the roof of the fourth ventricle, causes damage to the cerebellum by direet compression as it expands. It is a reasonable inference from this animal model that rhombie ventrieuloceles encountered in human developmental pathology, the present specimen included, arise by a similar hydrocephalic mechanism (Brodal, 1945; Brodal and tIouglie-Hanssen, 1959; Evrard and Caviness, 1974). The small pyramidal neurons of layer II, the last of the neocortical neurons to complete their migrations, are in normal relative position in the microgyrie cortex. This observation requires that the microgyric cortical defects in this case was produced by an insult occurring after migration to the cortex was complete, yet before the definitive pattern of tertiary convolution was established, i.e., between the 6th and 7th fetal months (Richman et al., 1973, 1974). This inference from anatomy is supported by the correlative clinical, pathologic studies of microgyria of Hallervorden (1949) and of Bankl and Jellinger (1967). The acellular microgyric layer I I I is reminiscent of the effect of ischemie laminar necrosis (t~iehman et al., 1973, 1974; Levine et al., 1974). The posterior medial regions of both cerebral hemispheres of the present ease were driven downward into the tentorial gap and engaged by the tentorium. This may have occurred consequent to hydroeephMic force acting supratentorially as well as to traction exerted on the brainstem from below by the expanding rhombie ventrieulocele. Had the posterior cerebral arteries been critically occluded by entrapment against the tentorium, bilateral cerebral infarctions would have been expected in the territory of the cortical defects encountered in the present ease (e. g., see Fig. 84A, Escourolle and Poirier, 1971). The occipital lobe encephalocele is a diverticulum of the lateral ventricle which extrudes through the left, more severe, cortical defect. Diverticula which are identical with respect to the point of egress from the ventricle, trajectory through
252
V.S. Caviness, Jr., and P. Evrard
the tentorial notch into the posterior fosse and tendency to impinge upon the cerebellum may come about as a consequence of severe hydrocephalus acquired in postnatal life (Sweet, 1940; Childe and McNaughton, 1942; Pennybacker and Russell, 1943; Russell, 1949). Similar diverticula of the occipital horns of the lateral ventricle also arise as a relatively late complication of hydrocephalus induced in experimental animals by ~ variety of teratogenes (Carton st el., i961; Duekett, 1972). I t is thus plausible that the occipital lobe eneephalocele in the present case came about as a consequence of hydrocephalic force, with the point of extrusion determined by a defect in the cerebral wall caused by infarction. Fragments of cerebellar tissue were scattered through the area of interface between the ventriculoeele and encephalocele, and the truncated peduncles were of substantial proportion. Presumably the developing cerebellum was destroyed by entrapment between the 2 cysts during the period of rapid tissue growth in the early third trimester. The degeneration of collateral cerebellar nuclei in the brain stem is reasonably considered secondary to loss of the connections with the cerebellum (Harkmark, 1956; Evrard and Caviness, 1974). The association of rhombic roof ventriculocele, occipital encephalocele extending into the posterior fosse and damage to the entrapped cerebellum is not unusual (Cleland, 1882 ; Monakow, 1899; Karch and Urich, 1972). The character of cerebral cortex at the base of the occipital lobe encephaloceles has, in general, not been described, although mierogyria has been specifically mentioned in single cases reported by Shryok and Knighton (1940), Karch and Urieh (1972), and Engel and Buehan (1974). Transtentoria] herniation of the medial aspect of the cerebral hemispheres with critical occlusion of the posterior cerebral artery, infarction of the inferior and medial region of the cerebral hemispheres and hydrocephalic extrusion of a ventricular diverticulum through the mural defect may be a general pathogenic sequence for all such cases. Occipital Iobe eneeplla~oceles, like spinal meningomyeloeeIes, are occasionally associated with variants of the Chiari deformity (Chiari, 1895), and two views, still hypothetical, to explain the pathogenesis of meningomyelocele have been advanced to explain the origins of the encephaloceles as well. The first, originally proposed by yon 1%ecklinghausen (1886), holds that a mesenchymal defect of undetermined origin is primary and that neural tissue expands secondarily through the resulting bony defect. Even before the end of the last century this theory was considered untenable by both experimental embryologists and developmental pathologists, because of the relatively greater precocity of development of neural with respect to mesenchymal tissues (reviewed by Monakow, 1899). Subsequent studies of normal developmental sequence (Streeter, 1915) as well as experimental studies (Holtzer, 1952, 1968; Holtzer and Detwiler, 1953; Holtfreter, 1968) contribute additional evidence that neural tissue determines cellular differentiation, augments growth and confers form upon adjacent mesenchymal tissues rather than the reverse. Bony defects like that in the present case come about, presumably, as a consequence of focally directed pressure leading to bony erosion, as is known to occur in postnatal life (gupe, 1938). In general, such bony defects occur in or near the occipital fissure where bony union is delayed, presumably a point of relative weakness during early development (O'lgahiIley, 1952).
Occipit~al Encephalocele
253
The second t h e o r y holds t h a t occipital lobe encephaloceles come a b o u t as a consequence of failure of closure of the n e u r a l t u b e (Campbell, 1948). W h a t e v e r the role of such a n e v e n t i n the d e v e l o p m e n t of spinal defects, it could n o t be the morphogenetic m e c h a n i s m of the encephaloceles e n c o u n t e r e d in the p r e s e n t a n d similar specimens because the position of the defect i n no sense corresponds to the closure line of the n e u r a l t u b e (Karch a n d Urich, 1972).
References Bankl, H., Je[linger, K. : ZcntralnervSse Sch~den nach fetaler Kohlenoxydvergiftung. Beitr. path. Anat. 135, 350--376 (1967) Bering, E. A., Jr., Sato, 0.: Hydroce, ph~us: changes in formation and absorption of cerebro~ spinal fluid within the cerebral ventricles. J. Neurosurg. 20, 1050--1063 (1963) Bonnevie, K. : Hereditary hydrocephalus in the house mouse. I. Manifestations of the bymutation after birth and in embryos 12 days old or more. Skr. norske Vidensk.-Akad., I. Mat.-nat. K1.4, 1--32 (1943) Bonnevie, K., Brodal, A. : Hereditary hydrocephalus m the house mouse. IV. The development of the cerebellar anomalies during fetal life with notes on the normal development of the mouse cerebellum. Skr. norske Vidensk.-Akad., I. Mat.-nat. K1.4, 1--60 (1946) Brandesky, G. yon, Klick, A. : Encephalocele und hydrocephalus. Z. Kinderchir. 7, 583--589 (1969) Brodal, A. : Defective development of the cerebellar vermis (partial agenesis) in ~ child. Skr, norske Vidensk.-Akad., I. Mat.-nat. K1.3, 1--40 (1945) Brodal, A., Bonnevie, K., Harkmark, W. : Hereditary hydrocephalus in the house mouse. I[. The anomalies of the cerebellum: partial defective development of the vermis. Skr. norske Vidensk.-Akad, I. Mat.- nat. K1. S, 1 --42 (1944) Brodal, A., l-Iouglie-FIanssen, E. : Congenital hydrocephalus with defective development of the cerebellar vermis (Dandy-Walker syndrome): Clinical and anatomical findings in two cases with particular reference to the so-called atresia of the foramina of Magendie and Luschka. J. Neurol. Neurosurg. Psychiat. 22, 99--108 (1959) Cameron, A. H.: The Arnold-Chiari and other neuro-anatomical malformations associated with spina bifida. J. Path. Bact. 78, 195--212 (1957) Campbell, J. B. : Congenital anomalies of the neural axis. Amcr. J. Surg. 7~, 231--256 (1948) Carton, C. A., Pascal, R. R., Tennyson, V. M. : Hydrocephalus and vitamin A deficiency in the rabbit: general considerations. In: Disorders of the Developing Nervous System. W. S. Fields and M. M. Desmond (eds.), pp. 214--266, Springfield, Ill.: Ch. C. Thomas 196i Chiari, H. : Uber die Vergndcrungen des Kleinhirns, der Pons und der Medulla oblongata in Folge yon congenitaler Hydrocephalie des GroShirns. Denkschr. Akad. Wissensch,-naturw. K1.63, 71--116 (1895) Chitde, A. E., McNaughton, F. L. : Diverticula of the Ia~era[ ventricles extending into the cerebeIlar fossa. Arch. Neurol. Psychiat. (Chic.) 47, 768--778 (1942) Cleland, J. : Contribution to the study of spina bifida, encephalocele, and anencephalus. J. Anat. Physiol. 17, 257--292 (1882) Dandy, W. E., Blackfan, K. D.: Internal hydrocephalus. Amer. J. Dis. Child. 14, 424--443 (1917) Duckett, S.: Teratogenesis caused by tellurium. Ann. N.Y. Acad. Sci. 192, 220--226 (1972) Emery, J. L., McKenzie, ~N.: Medullo-cervical dislocation deformity (Chiari II deformity) related to neurospinal dysraphism (meningomyelocele). Brain 96, 155--162 (1973) Engel, R., Buchan, G. C. : Occipital enccphaloceles with and without visual evoked potentials. Arch. Neurol. (Chic.) 30, 314--318 (1974) Escourolle, R., Poirier, J. : Manuel E16mentaire de 57europathologie. Paris: M~sson and Cie 1971 Evrard, P., Caviness, V. S., Jr. : Extensive developmental defect of the cerebellum associated with posterior fossa ven~riculocele. J. Neuropath. exp. Neurol. 88, 385--399 (1974) Gardner, W. J. : The Dysraphic Sta,tes. Amsterdam: Exeerpta Medica 1973
254
V. S. Caviness, Jr., and P. Evrard
Hallervorden, J. : t3ber eine Kohlenoxydvergiftung im Fetalleben mit EntwieklungsstSrung der ttirnrinde. Allg. Z. Psychiat. 124, 289--298 (1949) Hammock, M. K., Milhorat, T. H.: Recent studies on the formation of cerebrospinal fluid. Develop. reed. Child Neurol. (Suppl.) 29, 27--34 (1973) Harkmark, W. : The influence of the cerebellum on development and maintenance of the inferior olive and the pons. An experimental investigation on chick embryos. J. exp. Zool. 181, 333--371 (1956) Hochwald, G. M., Epstein, F., ~alhan, C., Ransohoff, J. : The rble of the skull and dura in experimental feline hydrocephalus. Develop. reed. Child Neurol. (Suppl.) 27, 65--69 (1972) Holtfreter, J.: Mesenchyme and epithelia in inductive and morphogenetie processes. In: Epithelial-Mesenchymal Interactions, R. Fleischmajer and R. E. Billingham (eds.), pp. 1--30. Baltimore: Williams and Wilkins 1968 ttoltzer, H. : An experimental analysis of the development of the spinal column. Part I. Response of pre-cartilage cells to size variations of the spinal cord. J. exp. Zool. 121, 121--147 (1952) Holtzer, H. : Induction of chondrogenesis: A concept in quest of mechanisms. In: EpithelialMesenchymal Interactions. R. Fleischmajer and R. E. Billingham (eds.), pp. 152--164. Baltimore: Williams and Wilkins 1968 Holtzer, H., Detwiler, S. 1~.: An experimental analysis of the development of the spinal column J. exp. Zool. 128, 335--369 (1953) Ingraham, F. D., Scott, H.W.,Jr. : Spina bifida and cranium bifidum. Hew. Engl. J. Med. 229, 108--114 (1943) Jupe, M. H. : The reaction of the bones of the skull to intraeranial lesions. Brit. J. Radiol. 11, 146--164 (1938) Karch, S. B., Urich, H. : Occipital encephalocele: A morphological study. J. neurol. Sei. 15, 89--112 (1972) Klick, A., Brandesky, G. : Durch eine 5~embrana interventricularis bedingter Hydrocephalus mit Encephalocele. Zbl. allg. Path. path. Anat. 112, 584--589 (1969) Laurence, K. M. : The natural history of hydrocephalus. Lancet 1958 iI, 1152--1154 Levine, D. N., Fisher, M. A., Caviness, V. S. Jr. : Porencephaly with mierogyria: A pathologic study. Aeta neuropath. (Ber].) 29, 99 113 (1974) Lorber, J. : The prognosis of occipital encephalocele. Develop. med. Child Neurol. (Suppl.) 13, 75--86 (1967) Lorenzo, A. V., Page, L. K., Watters, G. V.: Relationship between eerebrospinal fluid formation, absorption and pressure in human hydrocephalus. Brain 98, 679--692 (1970) MacKenzie, N. G., Emery, J. L. : Deformities of the cervical cord in children with neurospinal dysraphism. Develop. reed. Child Neurol. (Suppl.) 25, 58--67 (1971) Mealey, J., Jr., Dzenitis, A. J., Hockey, A. A. : The prognosis of encephaloceles. J. Neurosurg. 82, 209--218 (1970) Monakow, C. yon: (~ber die MiBbildungen des Zcntralnervensystems. Ergeb. allg. Path. path. Anat. 6, 513--582 (1899) O'Neill, E. M. : Normal head growth and the prediction of head size in infantile hydrocephalus. Arch. Dis. Child. 86, 241--252 (1961) O'Rahilly, R. : Anomalous occipital apertures. Arch. Path. 58, 509--519 (1952) Penfield, W., Cone, W. : Spina bi/ida and cranium bi/idum. J. Amer. reed. Ass. 98, 454--461 (1932) Pennybacker, J., Russell, D. S.: Spontaneous ventricular rupture in hydrocephalus, with subtentorial cyst formation. J. Neurol. Psychiat. 6, 38--45 (1943) Recklinghausen, F. yon: Untersuchungen fiber die Spina bi/ida. Virchows Arch. path. Anat. 105, 243--330, 371--455 (1886) Richman, D. P., Stewart, R. M., Caviness, V.S.,Jr.: Microgyria, lissencephaly, and neuron migration to the cerebral cortex: An architectonic approach. Neurology (Minneap.) 28, 413 (1973) Richman, D. P., Stewart, R. M., Caviness, V. S., Jr. : Cerebral microgyria in a 27 week fetus: An architectonic and topographic analysis. J. Neuropath. exp. Neurol. 88, 374--384 (1974) Russell, D. S. : Observations on the Pathology of Hydrocephalus. MRC Publication No. 265. London: HMSO 1949
Occipital Eneephalocele
255
Shryock, H., Knighton, 1%.S.: Arhinencephaly with associated agenesis of the corpus callosum and other anomalies. Bull. Los Angeles neurol. Soc. 5, 192--201 (1940) Streeter, G. L. : The development of venous sinuses of the dura mater in the hmnan embryo. Amer. J. Anat. 18, 145--178 (1915) Sweet, W. H.: Spontaneous cerebral ventriculostium. Arch. Neurol. Psychiat. (Chic.) 44, 532--540 (1940) Taggert, J. K., Walker, A. E. : Congenital atresia of the foramens of Luschka and Magendie. Arch. Neurol. Psychiat. (Chic.) 48, 583--612 (1942) Wealthall, S. R. : An investigation of the factors involved in regulating ventricular size and the production of hydrocephalus. Develop. reed. Child Neurol. (Suppl.) 29, 1--11 (1973) Weller, R. O., Wigniewski, H.: Histological and ultrastructural changes with experimental hydrocephalus in adult rabbits. Brain 92, 819--828 (1969) Williams, B. : Is aqucductal stenosis a result of hydrocephalus? Brain 96, 399--412 (1973) Yakovlev, P. I. : Whole brain serial histological sections. In: Neuropathology: 1YIethods and Diagnosis, W. Tedesehi (ed.), pp. 371--378. Boston: Little Brown & Co. 1970 Dr. Verne S. Caviness, Jr. Eunice Kennedy Shriver Center for Mental l~etardation Inc. At the Walter E. Fernald State School 200 Trapelo Road Waltham, Massachusetts 02154 U.S.A.
18 Actaneuropath.(Berl.):Bd.32
