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Arquivos de Neuro-Psiquiatria

Print version ISSN 0004-282XOn-line version ISSN 1678-4227

Arq. Neuro-Psiquiatr. vol.63 no.3a São Paulo Sept. 2005

http://dx.doi.org/10.1590/S0004-282X2005000400011 

Brain tissue aspiration neural tube defect

 

Aspiração de tecido cerebral em casos de defeitos de fechamento do tubo neural

 

 

Luiz Cesar PeresI; Gustavo Henrique T. de Sales BarbosaII

Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto SP, Brazil
I
Associate Professor
II
Resident in Pathology. Grant support: FAEPA - Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, Brasil

Correspondence

 

 


ABSTRACT

The study aimed to find out how frequent is brain tissue aspiration and if brain tissue heterotopia could be found in the lung of human neural tube defect cases. Histological sections of each lobe of both lungs of 22 fetuses and newborn with neural tube defect were immunostained for glial fibrillary acidic protein (GFAP). There were 15 (68.2%) females and 7 (31.8%) males. Age ranged from 18 to 40 weeks of gestation (mean= 31.8). Ten (45.5%) were stillborn, the same newborn, and 2 (9.1%) were abortuses. Diagnosis were: craniorrhachischisis (9 cases, 40.9%), anencephaly (8 cases, 36,4%), ruptured occipital encephalocele and rachischisis (2 cases, 9.1% each), and early amniotic band disruption sequence (1 case, 4.5%). Only one case (4.5%) exhibited GFAP positive cells inside bronchioles and alveoli admixed to epithelial amniotic squames. No heterotopic tissue was observed in the lung interstitium. We concluded that aspiration of brain tissue from the amniotic fluid in neural tube defect cases may happen but it is infrequent and heterotopia was not observed.

Key words: brain heterotopia, neural tube defect, brain tissue aspiration.


RESUMO

O objetivo do estudo foi identificar qual a freqüência de aspiração de tecido cerebral e a existência de heterotopia nos pulmões de casos humanos de defeito de fechamento do tubo neural através da reação imuno-histoquímica para proteína fibrilar glial ácida (GFAP) em cortes histológicos de todos os lobos de ambos os pulmões de 22 casos de fetos e neonatos com defeito de fechamento do tubo neural. Havia 15 casos femininos (68,2%) e 7 masculinos (31,8%), com idade gestacional variando de 18 a 40 semanas (média= 31,8), sendo natimortos e neomortos 10 (45,5%) cada e 2 (9,1%) abortos. Os diagnósticos foram: Craniorraquisquise (9 casos, 40,9%), anencefalia (8 casos, 36,4%), encefalocele occipital rota e raquisquise (2 casos, 9,1%) e 1 (4,5%)caso de seqüência de disruptura amniótica precoce. Somente 1 caso (4,5%) apresentou células positivas dentro de bronquíolos e alvéolos em meio a células epiteliais amnióticas. Não se observou heterotopia no interstício pulmonar. Concluímos que a aspiração de tecido encefálico do líquido amniótico pode ocorrer em casos de defeito do fechamento do tubo neural, mas são infreqüentes e heterotopia não foi observada.

Palavras-chave: heterotopia cerebral, defeito do fechamento do tubo neural, aspiração de tecido cerebral.


 

 

Brain tissue nodules in the lungs are rare and seen generally associated with neural tube defects1. Its pathogenesis is controversial and speculative. The two major hypotheses are aspiration of brain fragments after disruption in neural tube defect (NTD) cases2 and neural tissue migration defects during embryogenesis3. Neoplasia4 and brain tissue embolism2,5-8 have also been speculated but they do not explain such cases.

The main goal of this study was to determine how often could brain tissue be identified in the bronchial tree and lung parenchyma of NTD fetuses and newborn submitted to postmortem examination with conventional hematoxylin and eosin staining and immunohistochemistry for glial fibrillary acidic protein (GFAP) in order to determine if aspiration of disrupted brain could explain the occasional finding of brain tissue heterotopia in the lung.

 

METHOD

We analyzed retrospectively the lungs of 22 fetuses and newborn with NTD submitted to postmortem examination at the Department of Pathology, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil. One section of all lobes of each lung was histologically processed, embedded in paraffin from which 4 mm sections were examined by light microscopy using hematoxylin and eosin staining and immunohistochemistry for GFAP with the avidin-streptavidin method. The study was approved by the Ethics Committee of the University Hospital of our institution.

 

RESULTS

Table shows the clinical data, diagnosis and GFAP result for the 22 cases analyzed. There were 15 (68.2%) females and 17 (31.8%) males. Ten (45.5%) cases were stillborn, 10 (45.5%) cases were early neonatal deaths and 2 (9.1%) were abortuses under 19 weeks of gestation. Of the 10 neonatal death cases, 8 survived less than one hour, one survived 13 hours and another one 2 days. Gestational age ranged from 18 to 40 weeks, with a mean of 31.8 weeks. Craniorrhachischisis was the most prevalent diagnosis, with 9 cases, corresponding to 40.9%, followed by anencephaly, with 8 (36.4%) cases, ruptured occipital encephalocele and rachischisis, with 2 (9.1%) cases each and one case (4.5%) of early amnion band disruption sequence with destruction of the face, calvarium and brain. No brain tissue heterotopia was found in the lung parenchyma in any of the analyzed cases. Only case nr 13, a 28 week-old female stillborn fetus with craniorrhachischisis (4.5%) presented fragments of tissue positive for GFAP inside bronchioles and alveoli admixed to epithelial squames from the aspirated amniotic fluid (Figure). The hematoxylin and eosin stained section of this case showed small intraluminal masses of cells with round to oval nuclei and flat squames immersed in an amorphous background that did not present recognizable glial and neuropil features. Bronchial cartilage was also positive for GFAP in some cases.

 

 

 

 

DISCUSSION

Brain tissue heterotopia is a rare lesion and this fact has influenced our understanding of its pathogenesis. In the beginning of the 20th century it was interpreted as a neoplasia4 latter discarded9. Embolism of brain tissue may be seen after traumatic breech delivery7 and trauma to the head8 in any age. The brain tissue in this instance is found inside blood vessels and death occurs shortly leaving no time for implantation, if it was possible at all. Aspiration of brain fragments2,5-8 and modeling or migration defects are the most likely explanations10,11.

In this study, only one case in 22 (4.5%) showed brain tissue inside the bronchioles and alveoli. This tissue was admixed to the common epithelial squames from the amniotic fluid forming small masses. Its true nature was clearly depicted by the immunostaining for GFAP and would possibly have been missed if only hematoxylin and eosin stained sections have been used. Neuron specific enolase has been used to show neuronal differentiation1 and other antibodies such as neurofilament and synaptophysin may also be used. In fact, the routine use of immunohistochemestry in the lungs of cases presenting open NTD would allow the diagnosis of both aspiration, as seen in the present study, and interstitial implantation1.

There was no implantation or growing of the brain tissue but its presence indicates that aspiration may well be a mechanism that makes it possible. Anyway, the cases studied here had a gestational age higher than that expected for implantation to arise since the chance of brain tissue disruption is higher in early gestation. However, respiratory movements are fewer and the lungs exhibit only budding bronchi by the time brain fragments could be found more often in the amniotic fluid.

Brain fragments in the amniotic fluid are well documented in the literature with the transformation of early exencephaly to late anencephaly in animal models12. These fragments could surely be inhaled as well as swallowed by the fetus since respiratory movements and swallowing is present as early as 12 weeks of gestation13. Implantation of such fragments would require viable brain fragments and an adequate implantation surface. Soon after disruption at least part of the brain tissue fragments may well be viable. As the finding of brain tissue heterotopia is rare implantation is probably the limiting part of the process.

Swallowing of amniotic fluid is physiological and so brain fragments present in it could theoretically implant over the gastrointestinal mucosa and yet there is not a single report of its occurrence, maybe indicating that there are no favorable conditions for its implantation. Is the airway mucosa different? In case there are special conditions for its implantation, differently from other sites, why is it so rare? These questions are still unanswered demanding further studies.

An argument favoring implantation is its occurrence with ruptured teratomas, when glial elements may spread over and grow on the peritoneum14. In fact, there is a report of brain tissue implants over the abdominal surface of the diaphragm in a case of NTD and gastroschisis15 and more recently appeared a report on a fatal case of multiple brain tissue heterotopia in an otherwise normal baby, product of monochorionic monoamniotic gestation in which his twin brother presented anencephaly16.

Whereas, some cases reported in the literature indicate that aspiration may not be the only mechanism. The finding of brain nodules in the lung in cases with no open NTD10,17 may favor other mechanisms such as modeling or migration defect.

In conclusion, the data presented in this study show that aspiration of brain tissue fragments do occur and favors the aspiration hypothesis although we could not find evidences of viable tissue in order to implant and grow and also the aspirated fragments were inside airspaces not in the interstitium. Since there is yet no animal model for brain tissue heterotopia and human cases are rare other mechanisms such as a modeling or migration defect must not be discarded.

Acknowledgements - The authors thanks Mrs. Deise Lucia Cheska Simões for the technical help.

 

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Correspondence to
Dr. Luiz Cesar Peres
Departamento de Patologia
Faculdade de Medicina de Ribeirão Preto, USP
Avenida Bandeirantes 3900
14049-900 Ribeirão Preto SP - Brasil
E-mail: lcperes@fmrp.com.br

Received 15 September 2004, received in final form 17 December 2004. Accepted 7 March 2005.

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