Journal of Neuropathology and Expezimental Neurology Vol. 55. No.3 Cop yright 't"J J996 by the American Assoc iation of Neuropathologists March. 1996
pp. 348-356
Ependymal Changes in Sudden Infant Death Syndrome
JOAQuiN LUCENA, MD AND FEux F. CRUZ-SANCHEZ, MD, PHD, MRCPATH
Abstract. The ependyma may befall a variety of pathogenic noxae during fetal life. resulung in histological changes which may pers ist after birth but arc without clinical manifestations. Eight of a senes of 19 children who died suddenly and unexpectedly, where no explanation as to the cause of death wa s found at autopsy. were shown to have diverse histological features involving the ependyma. Five IJ.m paraffin-embedded brain tissue sections including frontal. temporal. oc cipital, and ventricular horns as well as the fourth ventricle were stained with hematoxylin-eosin (H&E) and luxol fast blue (LFB) . Immunohistochemical stams using antibodies to glial fibrillary acidic protein (G FAPl. virnentin and Sol 00 were also performed, Findings included areas of denuded and/or desquamated ependyma. rosettes in different stages of formation. vacuoles and/or pseudocysts, inflammatory changes consisting in macro- and microglial nodules in the subependyrnal layer. and gliosis. Chronic brain edema was seen in 4 cases. Our findings indicate that ependymal changes in sudden infant death syndrome (S IDS) cases belong to the prenatal or early postnatal period, thus providing. indirectly. a morphological substrate for the previous existence of a noxa that may also affect other CNS areas. and thus being in the position to produce cardiorespiratory control dysfunction .
Key Words: Ependyma: Neuropathology; Sudden infant death syndrome.
INTRODUCTION
The ependyma is an epithelial lining of neuroectodermal origin which borders the ventricular system including the central canal of the spinal cord . Severa) noxae may affect the ependyma and adjacent tissue both during gestation and al so subsequently. Changes of ventricuLar volume and/or ischemic and inflammatory processes and toxic agents may lead to structural changes, and it is known that the ependyma of humans and other mammalians does not regenerate at any age (I). Many pathological processes exert their effects during fetal development , producing some structural changes which may remain after birth even though clinically silent. At times, some of the resulting histological changes may be pointers to the original disease process.
Sudden infant death syndrome (SIDS) is defined as "the sudden death of an infant under one year of age which remains unexplained after a thorough case investigation, including performance of a complete autopsy, examination of the death scene and review of the clinical history" (2).
Current hypotheses suggest that SIOS results from abnormalities of central nervous system (CNS) structures regulating respiration and cardiovascular activity during sleep (3, 4). These abnormalities have been re-
From the Neurological Tissue Bank, Hospital Clfnico-Universiry of Barcelona (FCS) and Anatomical Forensic Institute. Barcelona (l L) .
This study was supported by the BIOMED-! program (PL931359) from the Commission of the European Communities. by a framework a~ment between Carburos Met:ilicos S.A. and Hospital Clinic for research in brain banking and by Comissto Interdepartarnental Per Recerca i Tecnologia (CfRIT) Generalitat de Catalunya.
Correspondence to: Dr FF Cruz-Sanchez. Banco de Tejidos Neurol6gicos. Servicio de Neurologia, Hospital Clfnico, Villnrroel 170. 08036 Barcelona. Spain.
lated 10 impairment in brain development mainly associated with maternal and environmental conditions traditionally known to be risk factors (5). However, in most instances, morphological findings confirming a particular association are found lacking .
Subtle tissue changes in various organs including the CNS have been described in SIDS (5). Increased brain weight (6), white matter lesions (7, 8) , and brainstern gliosis (9. 10) have all been reponed, but ependymal changes have not. None of the histological findings have ever been thought sufficient to explain SIDS deaths; however, tissue findings can be an indication of the impairment of several pathophysiological mechanisms involved in normal eNS development (5).
The present study describes pathological changes affecting the ependyma in 8 sros cases collected according LO a recently published research protocol (11). Similar findings have, to our knowledge, not been reported. These results further add to the hypothesis that some neuropathological changes found in SrDS are shared with those of other described developmental brain disorders (12) and dysfunctions (5).
MATERIALS AND METHODS
Twenty-eight infants who died unexpectedly between 1991 and 1994 were studied from a pathological point of view. including a detailed neuropathological examination. Age ranged from 19 to 330 postnatal days; 20 were males and 8 females. Death was explained in 9 cases (32%) (I I). The remaining 19 cases (68%) showed clinical. pathological , and medico-legal diagnost ic criteria of SIDS (2).
Brains were removed shortly after death and fixed in a 10% formaldehyde solution for 3 weeks (w) . The average postmortem delay was 14 hours (h). Subsequently, brains were cut coronally, sampled. and examined histologically according to a standardized protocol (l I). Eight cases (42%) showed diverse pathological features involving ependyma
348
349 THE EPENDYMA IN srns
TABLE I Some Clinical and Morphometrical Data of 8 SillS Cases
Bilth Moth. Head Head Brain Age Deliver weight APGAR Gesta age eire. eire. weight
N days. weeks g score tion years em (I) cm (2) g
I f 83 35 twin 1,160 g 6-8 2nd 26 yr 29 41 479 g 2 m 223 39 .2,800 g 8-10 3rd 36 yr 47 970 g 3 m 64 40 39 650 g 4 f 62 38 2,900 g 8-10 l st 27 yr 38 670 g 5 f 163 36 2,600 g 7-9 3rd 34 42 680 g 6 m 54 40 3,120 g 10-10 8th 38 yr 37 39 507 g 7 m 49 38 3,250 g 9-10 4th 32 yr 34 39 574 g 8 m 165 37 3,030 g 10-10 1st 22 yr 32 41 746 g
N: number of case and sex; f: female; m: male. Age: age at death. Deliver: gestation age at delivery. Gestation: number of pregnancies. Moth. age: age of the mother. Head eire (I): head circumference at birth; Head eire (2): head circumference at death.
TABLE 2 Ependymal Histological Features in 8 SillS Cases
Histological features 2 3 4 5 6 7 8
Ependymal epithelium Denuded ependyma + + ++ ++ Desquamated ependyma ++ + ++ + ++ ++
Hypertrophy
Rosettes +++ ++ ++ +++ ++ + Demiroseues ++ ++ ++ Ependymal rests +++
Subependymal layer Reactive or inflammatory changes
Microglial nodules ++ ++ ++ ++ Macroglial nodules ++ ++ ++ Gliosis ++ ++ ++ ++ ++ +++ ++ Residual germinal matrix + ++ +++ Perivascular infiltrates + Hemosiderin-laden macrophages + + ++
Non-inflammatory changes Vacuolation + ++ ++ ++ ++ Pseudocysts ++ + ++ + ++
Other CNS changes
Chronic edema ++ ++ +++ ++ Old subarachnoidal hemorrhagic
changes ++ Microglial nodules +
-: absent; +: mild or scant)'; + +: moderate; + + -t-: severe or abundant.
and were further studied. These cases were compared to 6 the ABC complex (all of them from Dako) were also percontrols whose death was explained but where the CNS was formed. not involved. Clinical data of these 8 cases are shown in Table I. RESULTS
Five urn sections of paraffin-embedded brain tissue from In spite of the absence of macroscopical abnormali
frontal, temporal, and occipital regions including ventricularties, including hydrocephalus, SIDS cases showed sevhorns and the fourth ventricle region were stained with heeral histological changes involving the ependyma whichmatox ylin-eosin (H&E) and luxol fast blue (LFB). Immuare summarized in Table 2. Most changes were found innohistochemical stains using polyclonal antisera for the glial
fibrillary acidic protein (GFAP, I :200) and S- 100 protein (S frontal and occipital horns. Controls did not show sig100. I :500), a monoclonal antibody for virneruin (I: 100). and nificant changes affecting ependyma. Table 3 shows the
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350 LUCENA AND cRuz-sANcHEZ
TABLE 3 Topographical Distribution of Histological Features in Ependyma of 8 SillS Cases and 6 Controls (C'I'L)
Frontal hom Temporal hom Occipital hom Fourth ventricle
Features SillS cn SillS en SillS cn SillS cn Denuded ependyma 4/8 ·0/6 0/8 0/6 4/8 0/6 [/8 0/6 Desquamated ependyma 5/8 0/6 1/8 0/6 4/8 0/6 0/8 0/6
Rosettes 4/8 0/6 2/8 0/6 4/8 t/6 3/8 0/6 Demirosettes 2/8 0/6 2/8 0/6 2/8 0/6 0/8 0/6 Ependymal rests 0/8 0/6 118 0/6 0/8 0/6 0/8 0/6
Microglial nodules Macroglial nodules
4/8 2/8
0/6 0/6
1/8 1/8
0/6 0/6 .
3/8 3/8
0/6 0/6
0/8 0/8
0/6 0/6
Gliosis 7/8 2/6 5/8 1/6 5/8 0/6 1/8 0/6 Residual germinal matrix 3/8 2/6 0/8 1/6 2/8 t/6 0/8 0/6 Peri vascu lar infiltrates 1/8 0/6 0/8 0/6 0/8 0/6 0/8 0/6 Hemosiderin-laden rnacrophages 3/8 0/6 0/8 0/6 t/8 0/6 0/8 0/6 Vacuolation 5/8 2/6 2/8 116 4/8 t/6 0/8 0/6 Pseudocysts 5/8 0/6 1/8 · 0/6 3/8 0/6 0/8 0/6
Immunohistological findings
GFAP 1/8 2/6 1/8 1/6 0/8 1/6 1/8 0/6 Vimentin 7/8 3/6 5/8 3/6 5/8 4/6 4/8 2/6 5-100 8/8 6/6 8/8 6/6 8/8 5/6 6/8 5/6
regional distribution of histological features including immunohistological findings in SIDS and controls.
In 4 cases, some areas of the ventricular surface appeared denuded, probably due to necrosis of epithelial cells (Fig. IA). In addition, 6 cases showed ependymal cells separate from the ventricular wall (Fig. IB). In most cases, these changes were accompanied by rosettes, macro/microglial nodules and gliosis in the subependymal layer. The presence of ependymal rosettes was a common feature. It was observed in different stages of their formation (Fig. 2). In some cases, rosettes formed sequestration and/or diverticuli of the ependymal surface. In other cases rosettes were derived from a space of discontinuous ependyma which formed a loop penetrating into the cerebral parenchyma. In 3 cases, demi-rosettes often appeared as a row of sub ventricular ependymal cells parallel to the surface (F ig. 3). Red blood cells, fibrin , and lymphocytes (l case) filled the central space.
In one case, 'abu ndan t immunohistochemistrynegative "curled" ependymal rests were observed in the white matter surrounding the lateral ventricle of the temporal horn, which were labeled " displaced ependymo-choroidal epithelial clusters" (Fig. 4) .
Ependyma from SIDS and controls showed irnmunoreacti vity for S- tOO and vimentin (Fig . 5) ~ $-100 expressed a cytoplasmic and nuclear pattern of immunestaining while vimentin showed a somatic pattern of positivity with perinuclear accentuation. Few epithelial cells showed somatic pattern of GFAP immunostaining (Fig. 6).
Micro- and macroglial nodules and gliosis of the sub-
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ependymal layer (Fig. 7) were observed. Some GFAPpositive glial nodules were of small size and located under the ependyma, occasionally protruding from and through the denuded spaces (Fig. 8) . Other nodules appeared larger and were composed of macroglial cells and were surrounded by GFAP-positive reactive astrocytes. In most cases, glial proliferation caused thickening of the germinal matrix and appeared to be GFAP positive (Fig . 6A). In one case, very few peri ventricular small vessels surrounded by mononuclear cells were
·seen. Hemosiderin-laden macrophages were fo und in three cases in the gliolic zone. In ' j cases, there was tis sue rarefaction of the 'subependymal white matter forming vacuoLes or spongiform changes. In 5 cases, large spaces resembling pseudocysts were also found. A degree of vacuolation up to the production of desquamation and stripping of the ependymal surface were seen (Fig. 9). Another pathological feature affecting the remaining central nervous system tissue was chronic edema (3 cases) with the presence of large astrocytes (Fig. 10), some with intracytoplasmic vacuoles and "lipidization." One case showed arachnoidal fibrous thickening and hemosiderin-laden macrophages. In one case, very few microglial nodules were seen in the white matter of the frontal part of the centrum semiovaie .
DISCUSSION
Previous studies have described two main categories of findings at the level of the eNS in SIDS, e.g, " de layed maturation" and .. solely pathological. " Maturation defects ranged from high dendritic spine density in neurons from hypoglossal nuclei (12), delayed ce
351 THE EPENDYMA IN SIDS
Fig. I. Ependymal surface in SillS cases: A (Top) . denuded ependyma (Case I, frontal hom). B (Bortorn). Ependymal cells separated from the brain tissue surface (desquamation) (Case 5, occipital hom). A: HE X200, B: HE X400.
rebral myelination (8), to atrophy of arcuate nuclei (13) and thickening of the cerebellar external granular layer (II, 14). Pathological changes such as gliosis (10), microglial proliferation (IS), and peri ventricular and subcorticalleukomalacia (7) have been related to different causes (5, 11) . Furthermore, neurochemical studies in SIDS have demonstrated neurotransmitter changes in the brainstem (16) which may have its morphological counterpart (5, 12, 17).
Ependymal changes observed in our cases were of some standing and consisted of a whole encompassing spectrum from damage to the ependymal epithelium to rosette formation. Denuded and desquamated ependyma, rosette and derni-rosette formation, ' thickening of subependymal layer with glial proliferation. as well as features consistent with previous hemorrhage are' pathological changes which may disturb the effective circulation and reabsorption of cerebrospinal fluid (CSF) (18) and/or alter the secretory function of ependyma in fetal life (1). Some changes could be related
Fig. 2. Different stages in ependymal rosette formation (Case 3, frontal born): A (Top). Loop formation which penetrates into the cerebral parenchyma (HE x6(0). B (Center). Sequestration of the surface ependyma (HE X400). C (Bottom). Discontinuous ependyma and rosettes in the subependyrnal layer: (HE X 400) .
to the increase in CSF voLume and/or pressure, leading to desquamation and to denuded ependyma, which may affect the normal milieu between ventricles and cerebral parenchyma (19, 20). However, ventriculornegaly
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352 LUCENA AND cRuz-sANCHEZ
Fig. 3. Ependymal derniroserte showing lymphocytic infiltrates in the open side space (upper) (Case 6, temporal hom). (HE x 400).
was not observed in any of the cases studied. Edema and vacuolation of the subependyrnal layer could be representative of degrees, or be the forerunner to the desquamation of the ependyma. Further studies of CSF in SIDS and controls, such as protein estimation and others, may be of value in the recognition of abnormalities in the flow of ventricular fluid and its composition .
Other mechanisms lending support to our f ndings include ventricular hemorrhage in early postnatal life
.as well as viral infections of the mother during pregnancy, causing damage to ependymal cells and subependyrnal tissue with the formation of micro/macroglial nodules and gliosis (18) . Most changes observed in our cases may be markers of pathological processes occurring in the perinatal period. Subventricu lar glial nodules may be the end result of the damage from a variety of causes (I). Residua of germinal matrix. hemosiderin-laden rnacrophages, and periventricu lar pseudocysts are pathological features related to focal, subependymal hemorrhage probably occurring in the perinatal period (21) . Ependymal rosettes and dernirosettes are secondary to ependymal damage (1. 20) and ependymal rests are rare features explained by the aberrant differentiation of some cells of the matrix layer (22).
Immunohistochemistry has been thought to be a suitable tool for the study of phenotypic differentiation of eNS tissue (23) and some types of brain tumors (24), thereby linking the an tigenic expression to ontogenesis (25). However, in the case of immature tissue and/or embryonal tumors such a link is difficult to substantiate (26, 27) . Despite the fact that some authors have found a possible link between the ependymal expression of virnernin to pathophysiological mechanisms of some
J Neuropaihol £rp Neural. Vol 55. March. 1996
Fig. 4. Displaced ependyma-choroidal epithelial rest or cluster in the cerebral white matter. (Case 7, temporal lobe) (GFAP x 100).
congenital disorders, (28) our results are inconclusive; the only positive assertion that can be made is that S 100 is a specific marker for the ependymal line, in agreement with other authors who studied ependymalderived tumors using the same antibody (29) . Ependymal remnants were consistently negative with all antibodies used, thus suggesting that they may represent the forerunners of ependyma, e.g. a preceding step in the ontogenesis .
Ependymal epithelium-like choroid plexus epithelium has absorptive properties (30). Its differentiation depends on an inductive action of the primitive ventricular neuroepithelial cells from the neural rube. The findings of GFAP expression in some epithelial cells could be explained on the basis of these concepts in a similar way of GFAP expression in choroid plexus cells (31). GFAP expression in ependyma and choroid plexus cells could be related to the ontogeny of the epithelium and/or to the product of degeneration in relation to age or to the type of cerebral pathology (edema, infarct, hemorrhage) . Assembling of GFAP in the same intermediate filaments has also been found using immuno-electronmicroscopy (32).
Features related to chronic edema were present in some cases. The presence of large hypertrophic astrocytes (some of them showing cytoplasmic vacuoles and lipid accumulation) is evidence of a reaction to brain damage (15, 33), including edema secondary to hypoxic mechanisms (34).
Astrocytes could phagocytose myelin or may be laden with lipids of yet unknown origin (35, 36) . Some authors have suggested that lipid-containing cells in infant brains may be the result of white matter damage in the periventricular region (37).
Very few histopathological features may be secondary
353 THE EPENDYl\1A IN SIDS
A
B
Fig. 5. Irnmunosrainings for 5-100 (A) and virnentin (B). Note the intense immunoreactivity of the ependymal epithelium for both antibodies showing a nuclear and somatic pattern for S-loo (arrows) (A) and a somatic pattern with perinuclear accentuation for virnentin (arrows) (B). (Case 8, temporal hom). A and B: X4oo .
to an acute process (see case 7) which is probably related to an infection at an ear ly stage of development. However, this case shared other changes such as chronic edema. vacuolation, and pseudocysts, which could explainchronic evolution of the initial morbid processes.
Ependymal changes in SillS were compared with 6 controls which did not show significant features affecting ependyma. Using a similarly sized group of controls is
difficult. SIDS is the first cause of postneonataJ infant mortality in developed countries. Deaths by accidents in the first year of life are. fortunately, very rare in developed countries and they are frequently related to intracranial damage. On the oilier hand, pediatric clinical autopsies are scarce in the first year of life.
Neurological tissue banks facilitate such research as in the research of other neurological disorders (38). In
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354 LUCENA AND CRUZ-SANCHEZ
Fig. 6. Immunostainings for GFAP showing intense positivity in few epithelial cells (arrows) and in the germinal matrix (bottom in the figure) (A) as well as in the subependymaJ layer (B). Note the presence of some hypertrophic astrocyies (large arrows). (Case 8, frontal hom). A and B: X400.
Europe. a brain bank network has been developed (0
serve as a bridge between clinicians and neuroscientists in the study of etiology and pathogenesis of central nervous system disorders (39). One of the objectives of this action is to acquire and adequately preserve brain tissue for SIOS research (II). Nevertheless, finding adequate controls is one of the most crucial difficulties in neuropathological SIDS research.
j Neuropatbol Exp Neural. Vol 55. March, 1996
SIDS has been considered a sleep-related disorder of cardiorespiratory control (3). Currently. it is thought that prolonged episodes of apnea during sleep are the final pathway resulting in these dramatic deaths (40). The age at death in SillS (90% under 6 months) suggests an important underlying mechanism involving growth and development (41).
In the first 6 postnatal months, the nervous system
355 TIIE EPENDYMA IN SIDS
Fig. 7. Macro-microglial nodule into the subependyrnal layer. (Case 2, frontal hom) (HE X200).
Fig. 8. Two GFAP·po.siove glial nodules protruding into a denuded ependymal space. (Case 3, occipital hom) (GFAP >(600) .
shows important maturative changes which are related to cardiorespiratory control (5); thus, SIDS occurs in a vulnerable postnatal period for the CNS. Epidemiological risk factors in SIDS indicate a non-optimal intrauterine environment supporting the hypothesis that brain dysfunction is originated in utero (5, 41). Other authors suggested prenatal virus infection (11, 16, 42). Variend and Pearse (43) observed that microglial nodules in a group of SIDS cases were related to an unrecognized intrauterine cytomegalovirus infection. Experimental studies demonstrated the potential for viruses to induce defects on the developing nervous system even with minor or clinically inapparent maternal or neonatal infection (20). Our findings further support these hypotheses , indicating the presence of histological changes of long standing and suggesting a prenatal or an early postnatal origin which
Fig . 9. Tissue rarefaction and spongy form changes in the subependymal layer. (Case 4, occipital hom) (HE x 200).
Fig. 10. Large reactive asrrocytes in the cerebral white mat ter showing intracytoplasmic vacuoles and cytopathological aspeel of lipidized cells. (Case 6. white matter of the centrum semiovale) (GFAP X 400).
may underlie CNS dysfunction invol ving cardiorespiratory control.
Most of our findings are in keeping with a pathological process involving the ependyma in SillS. Nevertheless, none of the infants presented clinical signs/symptoms before death and neither the eNS histopathological findings nor other findings were sufficient to explain death. The study and further characterization of these ependymal changes may well be of help in recognizing possible pathological processes which may alter the normal development of some CNS structures in a particularly vulnerable period.
REFERENCES l. Sarn at HB. Ependymal reactions 10 injury. A review . J Neuropathol
Exp Neurol 1995:54:1-15
J Neuropathol Exp Neurol, Vol 55. March. 1996
356
- i
LUCENA AND CRUZ--SA,NCHEZ
2. Willinger M. James LS. Catz e. Defining the sudden infant death syndrome (SIDS): Deliberations of an ex pen panel convened by the National Institute of Child Health and Human Development. Pcdiatr Pathol 1991: 11:677-84
3. Steinschneider A. Weinstein SS!, Diamond E. The sudden infant death syndrome and apnea/obstruction during neonatal sleep and feeding. Pediatrics 1982;70:858-63
4. Schechtman VL, Harper RM. Wilson AJ. Southall DP. Sleep apnea in infants who succumb to the sudden infant death ·synd rome. Pediatrics 1991;87:341-46
5. Kinney HC, Filiano J. Harper RM. The neuropathology of the sudden infant death syndrome. A review. J Neuropathol Exp Neural 1992:51: 115-26
6. Shaw CM, Sieben JR. Haas IE. Alvord Ee. Megalencephaly in sudden infant death syndrome. J Child Neurol 1989;4:39--42
7. Takashima S. Amstrong D. Becker LE. Huber J. Cerebral white matter lesions in sudden infant death syndrome. Pediatrics 1978;62: 155-59
8. Kinney HC. Brody BA. FInkelstein OM. Vawter G~ Mandell ~ oules FR. Delayed central nervous system myelination in the sudden infant death syndrome. J Neuropaihol Exp Neural 199150:29----48
9. Naeye RL. Brainstern and adrenal abnormalities in the sudden infant.dearh syndrome: Am J Clin Pathol 1966;66;526---39
10. Ki nney HC. Burger pe. Harrell FE. Hudson RP. ..Reactive gliosis" in the medulla oblongata of victims of the sudden infant death syndrome. Pediatrics 1983:72: 181-87
I I. Lucena J. Cruz-Sanchez FE The interest of the neurological tissue preservation for the investigation of sudden infant death syndrome. J Neural Transm I 993;(suppI)39: 193--205
12, Quattrochi JJ. McBride PT. Yates AJ. Brainsiern immaturity in sudden infant death syndrome: A quantitative rapid Golgy srudy of dendritic spines in 95 infants. Brain Res 1985:325 :39--48
13. Ftliano 11. Kinney He. Arcuate nucleus hypoplasia in the sudden infant death syndrome. J Neuropathol Exp Neurol 199251 :394-403
14. Lucena J. Tolosa E. Cruz-Sanchez FE Pathological study of the cerebellar cortex in sudden infant death syndrome. (Abstract) Brain Pathology 1994;4:396
15. Esiri 1\-1M. AI Izz.i MS. Reading Me. Macrophages, microglial cells and I-U-A-DR antigens in fetal and infant brain. J Clin Pathol 1991 ;44: 102---6
16. Kopp N, Chigr E Najirni M. et al, Le systerne nerveux central dans la mort subite du nourrisson: Donnees anatornochimiques. In: Dean M. Gilly R, eds. Mort Subite du Nourrisson. Progres in Pediatrie 6. Paris: Doin, 1989: 121-32
17. Takashima S. Becker LE. Delayed dendritic development of cute cholarninergic neurons in the ventrolateral medulla of children who died of sudden infant death syndrome. Neuropediatrics 199 1:22: 97 -99
18. Takano T. Mekata Y. Yamane T. Shimada M. Early ependymal changes in experimental hydrocephalus after mumps virus inoculation in hamster'>. Acta Neuropathol 1993:85:521-25
19. Johnson R1: Johnson KP. Hydrocephalus following viral infection: The pathology of aqueductal stenosis developing after experimental mumps virus infection. J Neuropathol Exp Neural 1968:27:591---606
20. Johnson RT. Effects of viral infection on the developing nervous system. N Engl J Med 1972:287:599--604
21. Valdes-Dapena M. McFeely PA. Hoffman ill. et aI. Histopathology atlas for the sudden infant death syndrome. Washington DC: Armed Forces Institute of Pathology: 1993
22. Tennyson YM. Pappas GO. Ependyma. In: Minckler J. ed, Pathology of the nervous system, Vol I New York: McGraw Hill. 1968:518-30
23 . Cruz-Sanchez FF, Rossi ML. Hughes IT. Coakham HB, Figols J. Eynaud PM. Choroid plexus papillomas: An immunohistological study of 16 cases. Histopathology 1989: 15 :6 1---69
24. Cruz-Sanchez FF, Garcia Buchs M. Rossi ML. et aI. Epithelial differentiation in gliomas. meningiomas and choroid plexus papillomas . Virchows Archi v B CeU Pathol 1992:62:25-34
25. Cruz-Sanchez FE Haustein J. Rossi Mi.. Cervos-Navarro J. Hughes IT. Ependyrnoblastorna: A histological , immunohistological and ultrasrrucrural study of five cases. Histopathology 1988: 12: 17-27
26. GuiloLa F. Immunohistochemistry in childhood brain rumors: What are the facts? Childs Nerv Syst 1990;6: I 18-22'
27. Cruz-Sanchez FE Rossi L'vIT... Hughes IT. Moss Tl-I . Differentiation in ernbrional neuroepithelial tumors of the central nervous system. .!:
Cancer 1991 :67(4}:965-76 28 . Samar HE. 0' Agostino A. Focal ependymal overexpression of vi·
mentin in Aqueductal Stenosis and Chiari malformations. Brain Pa thology (Abstract) 1994;4 :392
29. Cruz-Sanchez FE Rossi MI., Hughes n: Cervos-Navarro J . An immunohistological study of 66 ependymomas. Histopathology 1988;13,443-54
30. Russel D. Rubinstein U. Pathology of tumors of the nervous systern. London: Edward Arnold. 1989:394
3 I. Cruz-Sanchez FE Rossi ML. Choroid plexus papillomas (correspondence). Histopathology 1990; 17:185---89
32 . Wang E. Caincross JG. Lienz RKH. Identification of glial filament protein and virneruin in the same intermediate filament syste m in human glioma cells. Proc Natl Acad Sci 1984:S I :2l02---6
33 . Esiri MM. Urry P. Keeling J. Lipid-containing cells in the brain in sudden infant death syndrome. Devel Med Child Neural 1990 ;32: 319--24
34. Gadsdon DR. Emery JL. Farry change in perinatal and unexpected death. Arch Dis Child 1976;5 1:42-48
35 . Kepes J. Rengachary SS. Lee SH. Astrocytes in hernangyoblastoma of the central nervous system and their relationship with stromal cells. Acta Neuropathol (Berlin) 1979:47:99-104
36 . Cruz-Sanchez FE Rossi NfJ, Rodriguez Prados S. Nakamura N, Hughes IT Coak.ham HE. Hemangioblastoma: Histological and im munohistological study of an enigmatic cerebellar tumour. Histol Histopath 1990;5:407-l3
37. Banker BO. Larrcche Je. Peri ventricular leukornalacia of infancy. Arch Neurol 1962:7:386
38 . Cruz-Sanchez FF, Tolosa E. The need of a consensus for brain banking . J Neural Transm 1993:39(suppl): [--4
39. Cruz-Sanchez FE Ravid R. Cuzner ML. The European brain bank network (EBBN) and the need of standardized neuropathological criteria for brain tissue cataloguing. In: Cruz-Sanchez FF.et al, eds, Neuropathological diagnostic criteria for brain banking. Amsterdam: lOS Press. 1995 : 1-3
40 . Shannon DC . Kelly Of-!. SIDS and near SIDS . N Engl J Med 1982 :30:959--65
41. Valdes-Dapena M. Sudden infant death syndrome: Overview o f recent research developments from a pediatric pathologists perspec tive . Pediatrician 1988: 15:222-30
42. Summers CM. Parker. Je. The brainstem in sudden infant death syndrome. A postmortem survey. Am J Forensic Med Pathol 1981 :2: 121-27
43 . Variend S. Pearse RG . Sudden infant dealb syndrome and cytomegalic inclusion disease. J Clin Pathol 1986:39:383---36
Received May 15. 1995 Revisions received October 20. 1995 and November 10. 1995 Accepted December 5. 1955
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