obstetrical pathology

I have added the pancreas to the autopsy manual. My resources for creating these pages is currently limited. I am more than willing to have colleagues add their knowledge and suggestions to these pages by emailing me. I am posting the autopsy manual as a basis to develop a shared autopsy protocol for the stillborn research project (see research menu). Some conditions that cause perinatal death of liveborn infants, such as fetal hydrops, oligohydramnios and fetal growth restriction, also increase the risk of stillbirth. The manual considers findings and causes in these conditions, although briefly. The manual also does not develop an integrated picture of disease. I plan for the regular obstetrical pathology pages to accomplish that goal such as pages on maternal diabetes, macrosomia and the mechanisms of fetal growth restriction. 

            The stillbirth research protocol will include in situ MRI of the umbilical cord in fetal death, and a clinical history that looks in more detail at immediate factors that might in aggregate compromise the fetus and lead to a positive feedback loop that causes hypoxic or acidotic death. The primary goal of the study is to improve understanding and hopefully prevention of stillbirth of currently unknown cause. However, as in any perinatal autopsy, there is the hope that more general knowledge of intrauterine disease will also be found, such as insight into how intrauterine factors cause adult disease or how sublethal events might lead to or predispose to permanent neurologic injury. For an example of the former, I recall Dr. Mike Ross presenting at a NICHD Diabetes in Pregnancy meeting data on a rat model of maternal hyperglycemia that seemed to change the satiety response of the offspring. He presented slides showing associated brain abnormalities in the arcuate and related hypothalamic nuclei. I could not find a publication cite for this work, but if the results held, it would be possible to prospectively look for similar brain changes at autopsy of infants of diabetic mothers. 

I have added a new page to the autopsy manual on the thymus. My goal with the autopsy manual is to provide a basis for analysis of stillborn autopsies. As such, topics of malformation are covered only superficially if at all. In infants with malformations, it is important to discover the mechanism of death as the malformation per se is not a cause of death. Some malformations may predispose to intrauterine death such as those causing oligohydramnios. However, I am also seeking to understand the biological significance of the organ findings in order to integrate them into a more complete picture of the timing and mechanism of death. The manual will reflect those concerns.

            There are now new menu “widgets” to make accessing the pages easier. 

            I have posted an addition to the autopsy manual on the adrenals. I want to expand the autopsy section as a basis for a protocol for the proposed stillbirth study. Unfortunately, I had already discarded most of the organ and malformation specific images that I had, including hydrops, triploidy, etc. I will need help to expand the types and numbers of images. I think published images are critical to helping standardize pathological diagnoses. A single example of a lesion does not in itself present the variety seen in actual cases.

            Some of the text is probably dated, and I do not yet have access to a library. I still wanted to start the process of posting subheadings to the manual, hence the new page. I also added the Chronic Histiocytic Intervillositis page to the new research menu. The proposed research project is at the end of the page. 

            I have updated the e-book work in progress, but I still need to improve the formatting and navigation. I have renamed the “page” as “Chronic Histiocytic Intervillositis”. It is not yet the time to create an open source digital placental pathology book. In writing the draft, I did see how important it is to have many case  illustrations, even better if they could be whole slides. I think for pathologists to understand CHIV, they need to see a broad sample of the overlying pathologies and of the difficulties in assigning percentage borders to the diagnosis.

I still want to find participants for a multi-institutional study of CHIV. As with the stillbirth study, I hope to pilot a study at Magee after I start there in February. A draft of the proposal for the study is in the  “Massive Chorionic Intervillositis” page. I am also posting same draft proposal below on this blog. I still need to add references, and the proposal is incomplete. I am open to comments and suggestions. Thanks. 

Draft of a Proposal to Study CHIV

Background: 

            The lesion is defined by a consensus to have clusters of monocytes in more than 5% of the intervillous space. The monocyte clusters should contain at least 80% monocytes. There  may be heterogeneity in the distribution of intervillous monocytes. The lesion has an association with increased perivillous fibrinoid and villitis of unknown etiology. There is no clear association of obstetrical outcome with these histological features, although there is some evidence that monocytes filling more than 50% of the intervillous space are associated with more severe outcomes.

            Associated clinical outcomes include a high incidence of fetal loss at all gestations, but greater in the first and second trimester, fetal growth restriction, and recurrence in multiple pregnancies. The growth restriction is often early onset and may be associated with oligohydramnios. There may be an elevation of maternal serum alkaline phosphatase above normal pregnancy values.

            An immune origin of the lesion has been hypothesized. There may be an association with maternal autoimmune disease, especially anti-phospholipid syndrome, and with anti-HLA antibodies. The microvillous border of syncytiotrophoblast can be immunostained with c4d, a marker of antibody initiated fixation of complement. 

            Many treatment regimens have been used to prevent recurrent fetal loss, and anecdotally have resulted in a live born infant. These have included combinations of low dose aspirin, low molecular weight heparin, prednisone and hydroxychloroquine. No treatments have been demonstrated to be superior. 

            There is no standard pre-delivery method to diagnosis the lesion in an index pregnancy. Measures of early onset growth restriction are consistent with the lesion in pregnancies after a primary histologic diagnosis. The histologic lesions show variety and it is possible that the lesion is a common pathway of different etiologies. Only one, malaria, has been specifically identified. A better understanding of the pathogenesis of the lesion is needed.

            The goal remains to find a specific test for the lesion prior to delivery, and an effective treatment. Even though the lesion is infrequent (less than .5% prevalence), it can cause recurrent fetal losses in some mothers. 

Aims of the study

            Part 1: Retrospective study of the histology: 

1. Develop a quantifiable method of measuring intervillous monocytes, perivillous fibrin/fibrinoid, and VUE
2. Utilize CD 68, anti T cell, and c4d staining on cases and develop quantifiable measures.
3. Correlate the quantified measures of part 1.2  with obstetrical outcomes: first trimester fetal death, second trimester fetal death, third trimester fetal death, fetal growth restriction in the second trimester, fetal growth restriction in the third trimester, history of recurrent pregnancy loss, and history of recurrent CHIV. 
4. Correlate quantified histologic measures with treatment, and if possible from placental samples from the same patient before and after treatment.

            Part 2: Prospective study of mothers with a history of previous CHIV or with early onset severe fetal growth restriction.

1. Obtain maternal serum at first visit, at time of delivery, and before and after start of treatment to test for markers of the disease including alkaline phosphatase, serum complement panel, and red cell c4d. 
2. Perform an auto-antibody panel including anti-phospholipid and anti-HLA
3. Save serum to explore other markers of monocyte activation, of syncytial trophoblast injury, or of auto/allo-antibodies to trophoblast antigens
4. In addition to routine specimen processing, prepare tissue of further basic research on CHIV including frozen placental tissues, and monocyte extraction from placenta

Part 3: Prospective Clinical trial

1. Trial comparison of at least two therapy regimes against historical controls 

Methods:

Part 1.1 

            The slides from cases of previously diagnosed CHIV (and gestation matched controls) are scanned and areas are selected that do not contain lesions or non-placental tissue. The size of the areas on each sample slide are calculated. The number of intervillous monocytes, foci of VUE, and area of pervillous fibrinoid are calculated for each area and summed area of each case. A shared software solution will be developed to use image analysis to perform this procedure. The range of values for the measured variables for each case in different slides of the same sample will also be recorded.

Part 1.2 

            From the same cases above, additional slides will be cut for immuno-staining with CD68, T-cell markers, and c4d along with controls. The same procedures will be used to select areas to evaluate as in part 1.1 . Then, software will be developed to count each of the CD68 cells in the intervillous space, the T-cells in the villi, and linear extent of c4d staining along the villous surface.

Part 1.3

            The various histological measures will be compared to the major clinical outcomes:  first trimester fetal death, second trimester fetal death, third trimester fetal death, fetal growth restriction in the second trimester, fetal growth restriction in the third trimester, history of recurrent pregnancy loss, and history of recurrent CHIV. Statistical analysis will look at independence of the variables, and the best cluster of variables to “predict” the clinical outcome and, if possible, using ROC analysis to create a diagnostic score.

Part 1.4 

            Using the best cluster of variables to “predict” outcome, the measure of these variables in the specimens before and after treatment in an individual patient are tested against the null hypothesis that treatment did not alter the diagnostic score. 

Part 2.1

            The serum values will be compared to controls without evidence of early growth restriction, or history of CHIV, and to cases with evidence of early growth restriction with and without the diagnosis of CHIV. The goal is to find a correlation of the serum markers with the diagnosis of CHIV.

Part 2.2

            These antibody screening will be from routine clinical laboratory procedures. The prevalence of such antibodies in CHIV will be calculated. In addition, cases with autoantibodies will be stratified in comparisons with obstetrical outcomes, measures of alloantigen response, and of treatment outcomes in part 3.

Part 2.3 and part 2.4 

            Future studies into the pathogenesis of the disease depend on researcher initiative. A sample proposed study that hypothesized an alloantibody to a paternal microvillous antigen, could utilize frozen section slides of placentas including those from the patients and controls. An Fc receptor blocker would be applied to the slides, and then CHIV and control serums applied to the slides. They would then be rinsed, and a fluorescent labeled anti-human IgG would be applied. Positive fluorescent staining would be evidence of specific anti-trophophoblast antibody if the control serums were negative. Further studies could be designed to identify the antigen.

Part 3: The high recurrence of fetal death in mothers with identified CHIV in a prior pregnancy precludes an untreated group given anecdotal reports of successful treatment. A panel of obstetricians would decide on the best way to approach comparing randomly assigned treatment groups. The results of the study would also be stratified by various anatomic and clinical pathological variables elucidated in parts 1 and 2. 

Statistical analysis:

Institutional resources:

Sample patient consent:

Since last week, I added some photomicrographs, but stopped at case 4. There are 14 cases completed, with 47 images. I stopped uploading because adding one at time creates a long list that would be hard to navigate. The idea was to have a way to choose a case and enter that case via a header. For pathologists to understand the difficulties of interpreting CHIV, a large selection of images (or whole slide scans) is needed. For pathologists new to the diagnosis, some guidance is needed, as the spectrum is really quite wide. I also wanted to show the value of c4d staining which was not really conveyed in the statistics of the published article. WordPress has a image gallery option but I couldn’t get it to operate the way I needed.

There is now a literature review, with comment and a spreadsheet in Excel. Initially the information was summarized as text, but a spreadsheet will be more useful, I have not yet gotten the Boyd and Redline article into the spread sheet, so I left the text information for now.

I started a Comment section trying to digest the studies in a way that would lead to an algorithm for writing a Final Diagnosis report. There was some overlap here with my section of hypothesized pathogenesis that I included last week. Both these sections will need input from an editorial group.

The final goal is to use all of the publications, case examples, and hypotheses to build a research protocol to investigate the pathogenesis and develop more specific diagnostic testing, not to mention the hope of comparative therapeutic trials.

Currently, the MSWord outline does not translate well into WordPress, and none of the functional ability to dig deeper in the outline is present. In MSWord, the reader can select the depth of the outline that shows on the page.

Until I get the technical details resolved, I will stop adding material. Ideally, I can find a partner for creating this concept of a digital open source book. If anyone wants to see the case images and legends, email me and I can set them up on Dropbox.( bendonrw@gmail.com)

Last weekend was the Society of Pediatric Pathology, and no blog. This week I want to discuss a project to build on the Dublin consensus conference book. As a reward for my contributing to the book, I was at first disappointed, all I got for my effort was an electronic copy of the book, instead of a print copy. However, in reading the digital book, I became convinced that it is potentially key to building a better way for placental pathologists to communicate. I have not consulted any editors or authors of the Pathology of the Placenta Dublin consensus book. By taking advantage of digital media, we can create a construct that can:

1. Provide a medium to update the entry and constructively evaluate new papers/presentations
2. Have an ongoing editorial group for each section that can include experienced, as well as, younger faculty, meeting (virtually) on a regular basis.
3. Provide specific algorithms for evaluating a case with a presumed diagnosis
4. Provide assistance with formatting the final diagnosis report]
5. Provide an area for uploading cases and opinion for the editorial group to evaluate
6. Have a non-linear format that would allow, like an outline, for deeper pursuit of a topic, including numerous photo micrograph or even whole slide examples
7. Use hyperlinks to other relevant sections rather than repeating material
8. Provide a forum to recruit for collaborative studies
9. Provide analysis of studies in a format that would aid meta-analysis e.g. type of study, population number and criteria, including controls, outcome criteria, numerical results. 
10. Provide a clear definition of the clinical significance of the entity

I cannot now actually digitally format the “book” as I envision it, but I have a first draft model below for an entry. I have not consulted yet with any of the editors/authors of the Dublin book. I tried creating a mock-up in MSWord in outline format for Chronic Intervillositis of Unknown Etiology. I did not complete this sample section. I used an old piece that I had for the history section, and analyzed my own paper, but I intend to complete more over the next week. This topic was not a random choice. I am working on developing a collaborative study of this entity in the near future. I would appreciate any thoughts from others. Until I have a way to write on the site directly, please send comments to bendonrw@gmail.com.

(I uploaded the Work in Progress to the pages. WordPress has changed its tools and editing. The outline is scrunched into the blog space, and is too narrow and their heading choices are too large. This will take work. Also I do not know how to control the placement of the page headings. I will have to work on all of this as well as content.)

Proposed format for 

Consensus name of the lesion:  

            Justification of name:

Indicators for placental examination;

History of the lesion/disease/concept, including nomenclature:

Diagnostic features

            Gross

            Diagnostic microscopic features

            Other associated micro pathology

            Ancillary testing on specimen:

                        Available

                        Indicators for use

Differential: With comparison micrographs

Pathogenesis:

            Associations with evaluation of quality of study

            Relevant basic science

            Major unanswered questions

Clinical understanding:

            Presentation: includes gestation

            Laboratory features:

            Immediate outcome

            Recurrence

            Treatment

            Maternal health:

            Major unanswered questions:

Final Path diagnosis and comment:

            Consensus term

            Extent and Severity of the lesion

            Special studies

            Relationship to other findings

            Clinical Actions

                        For the infant

                        For the mother

                        For quality assurance

                        For research

                        For clarification and confirmation of clinical events

Review of published studies

Research Proposals

            Ongoing

            Suggested

                        Basic Science

                        Clinical Management

Public Upload area:

New Comments/opinion:

Up loaded cases:

New or overlooked papers/studies:

            10/15/20 I am back to writing the blog. I have accepted a position at Magee Woman’s Hospital as a placenta/perinatal pathologist to start Feb 1. I am very excited about the potential to accomplish some cherished research projects at Magee. For my interview seminar, I presented the stillbirth project I had proposed on this blog. The main novelty of the project is to obtain an MRI of the infant in the uterus after death, but before delivery, in order to look at umbilical cord configurations. The other novelty is to ask questions about immediate events surrounding the presumed time of death, such as changes in fetal movements, sleep positions, eating and gastrointestinal issues etc. that have bearing on the theory that stillbirth may be due to multiple contributing factors. The idea is that partial hypoxia/acidosis can reach a tipping point in which hypoxic/acidotic cardiac failure leads to a positive feedback loop with decreasing placental perfusion leading to decreasing cardiac output, eventually leading to death. I have posted an edited version of this talk as a new page on the blog “Invitation to a study of stillbirth”

            I did not try to write the methods for the study. Instead the proposal acknowledges the need to first find a group of people who have multiple different knowledge bases. The project will need commitment from radiologists, and obstetrical caregivers, but it would also benefit from the input of basic scientists, parents of stillborn infants, bioengineers, behavioral scientists etc. The proposal needs to be hashed out by a group that would want to participate in developing the study. I plan to pilot the study at Magee, but I don’t think it is too early to find support at other institutions. I think the arguments in the talk make a reasonable case for cord accidents as a cause of stillbirth. I still have to accept that I could be wrong, and that the pilot MRIs do not find an explanation of stillbirth. The problem of the high incidence of the stillbirth remains, and the research would continue.

            As part of the project that will improve our understanding of stillbirth, I want to collaborate with other pathologists to develop autopsy protocols that are very specific to understanding the mechanisms of stillbirth by identifying and quantifying the evidence of the physiology leading to death. I have already posted on the blog some of my autopsy protocols for gestational age determination, postmortem retention and measurements. Below is a preliminary draft of an approach to the autopsy for this study. I would be grateful for any input.  A stillbirth specific placenta protocol will also be needed to quantify the placental contribution to fetal hypoxia or other mechanisms of death.

Draft of an stillbirth specific autopsy protocol:

            Stress: adrenergic/corticosteroid elevation:

                        Adrenal weights, adrenocytomegaly, thickeness fetal to adult cortex.

                        Thymic weights, histology how to measure cortical v medulla, eosinophils

                        Islet somatostatin

            Heart failure:

                        Measure thoracic cavity effusions

                        ? measure on skin, radiology, weight after blanket

                        Pulmonary weight to body or brain

                        Measures of cardiac dilatation, muscle cell morphology

                        Liver weight: brain weight, spleen weight

            Gasping:

                        Intrathoracic petechia

                        Asp amniotic squames

                        Asp mec or blood\      

                        Airway configuration/expansion

                        Diaphragm?

            Previous asphyxia:

                        Pap muscle heart, necrosis or calci, other endocardial necrosis

                        Brain lesions any destructive, necrotic lesions, white or gray, various nuclei (basal ganglia, lateral geniculate, acrcuate and, hypothalamic), , hippocampus, and multiple samples of neocortex 

            Shock

                        Adrenal hemorrhage

                        Diffuse petechiae and small hemorrhages

                        Vasodilation

                        Liver sinusoidal thrombi

            Blood loss

                        Pallor, how to measure

                        Color loss from postmortem hemoglobin diffusion

                        Erythropoetic expansion

                        Nrbcs in blood

                        Hemosiderin in spleen

                        Internal hemorrhages esp cranial, abdominal from liver, tumor

            Infection

                        Spleen B cells

                        Histological organisms

                        Pmns in lung, gut

                        Microorganism identification, incl STDs

            Nutritional loss

                        Brain body weight

                        Adipose thickness skin, over kidney

                        Muscle fiber diameter

                        Growth plate lines

            Ductal closure

            Hyperthyroidism

                        Size

                        Histology

            Thrombophilia

                        Thrombi in major and large vessels

                        Infarcts esp brain

            IDM

                        Adipose

                        Isler hypertrophy/ insulin

                        nrbcs

                        Muscle diameter

            Cytotoxic

                        Lack of liver EMH

                        Cortical thickness

                        ? Gi tract

            Reliability of histology v Genest

            Organ weight changes with retention

            Fluid shifts with retention

            Tests other than histology, lung culture, radiograph, how to save, such as blood smear, H1ac, DNA, most other biochemistry must deal the 98.6F autolysis, when is it regular enough to extrapolate.

A recent New York Times headline stated “Children born by cesarean section may have important differences that affect their neurodevelopment”, based on a recent JAMA article¹. The neurodevelopmental outcomes that were correlated were autism and attention deficit disorder.

The article goes on to explain that this is an association not a cause, and that conditions requiring a Cesarean section could cause the association, rather than the procedure itself. The article is a meta-analysis and does not subgroup Cesarean sections, for example, those done for non-reassuring fetal heart tracings. I think this is an important piece of missing data. My concern is that experimental evidence has demonstrated that very minimal hypoxic stress to a pregnant animal can cause pontosubicular neuronal necrosis in the fetus. I will discuss the specifics of the lesion below, but the importance is that relatively mild episodes of hypoxia/ischemia in the infant brain can cause loss of specific groups of neurons. In the typical sheep experiment, this lesion occurs after just 10 minutes of complete umbilical cord occlusion^2-4. It is not a stretch to suggest that some of the infants undergoing emergency Cesarean sections have equivalent episodes of hypoxia.

Pontosubicular neuronal necrosis is a pathological lesion in which individual neurons in the basis pontis and in the subiculum show karyorrhexis (breaking apart) of the cell nucleus. In both experimentally produced lesions and in autopsy tissue, the karyorrhectic neurons demonstrate evidence of apoptosis^5-8. These neurons are responding to the hypoxic event with basically programmed cell death, or as sometimes put, cell suicide. The cell death is not the direct result of hypoxia or acidosis. As discussed in my blog pages on primate models and particularly on Ron Myers model, neuronal necrosis occurs in a stereotyped pattern of progressively recruited areas of the brain the longer the infant monkey is completely hypoxic. This is a different pattern from the extensive coagulation necrosis seen in the white and gray matter with partial hypoxia. This latter pattern is typical of cerebral palsy. Myers proposed that the sequence of areas reflected damage starting with the most metabolic active areas progressing to less active areas. These studies evaluated neuronal necrosis starting at 14 minutes of total asphyxia, and did not include pontosubicular necrosis, but the appearance of the more advanced lesions is very similar to those in the pons and subiculum.

As a pathologist, I have often seen pontosubicular necrosis in stillborn infants in which an anatomic cause of death was not found (Fig 1).

In these cases it is not unreasonable to speculate that the lesion reflects as recurrent or persistent hypoxic event prior to the final lethal event. Others have published on the finding of neuronal necrosis in stillbirth^9,10. Since even apoptosis takes time, the lesion was not likely the result of the immediate episode that caused death. Interestingly, the lesion is found in neonates with more chronic causes of hypoxic (and hyperoxic) episodes and must be part of an ongoing process¹¹. The dead cells are then removed without inflammation or scarring. The scattered, necrotic, cells that I see as a pathologist would not be detectable by the usual clinical imaging techniques. We simply have no way of knowing if pontosubicular necrosis has occurred in a living infant.

It is unclear if neurons are later replaced after pontosubicular necrosis or if a specific population of cells is permanently reduced. In my examination of the slides, the karyorrhectic cells appear to be in Sommer’s sector (CA1) of the hippocampus, the anatomic area adjacent to the subiculum, but I am not a neuropathologist, and the brains are very small. In either location, this is an area that appears to be important in correlating positional information with other cues¹². Its role in memory and emotion is likely complex. Uncal lesions in the monkey brain lead to a lack of response to social cues (The uncus is in physical continuity with the hippocampus.)¹³. A reasonable hypothesis is that loss of certain neurons could influence attention and response to environmental clues. Mostly as an aside, the evolutionary basis if any of cell apoptosis in the developing brain to hypoxic stimuli is curious, but we know that the developing brain is in some sense a competitive environment for neurons, and perhaps apoptotic pathways may be hijacked by the external fetal hypoxic event.

The importance of noting the risk of subtle neuronal necrosis is important. If neuronal necrosis is causing neurodevelopmental disease with relatively mild fetal hypoxia, then anti-apoptotic therapy may be better. In the experimental worm, C. elgans mutations of the insulin/ insulin growth factor homolog DAF-2 can help prevent apoptosis ¹⁴. Identifying similar mutations in humans that could influence susceptibility to neuronal necrosis might allow more aggressive obstetrical care. More information on the mechanism and outcome of pontosubicular necrosis is needed. Further investigation of subtle neuronal necrosis following brief fetal hypoxia may provide insight into one possible lesion for a link between Cesarean section and neurodevelopmental pathology of autism and attention deficit.

 

 

References:

1. Zhang T, Sidorchuk A, Sevilla-Cermeno L, et al. Association of Cesarean Delivery With Risk of Neurodevelopmental and Psychiatric Disorders in the Offspring: A Systematic Review and Meta-analysis. JAMA Netw Open 2019;2:e1910236.
2. Mallard C, Gunn A, Williams C, Johnston B, Gluckman P. Transient umbilical cord occlusion causes hippocampal damage in the fetal sheep. Am J Obstet Gynecol 1992;167:1423-30.
3. Keunen H, Deutz NE, Reempts JL, Hasaart TH. Transient umbilical cord occlusion in late-gestation fetal sheep results in hippocampal damage but not in cerebral arteriovenous difference for nitrite, a stable end product of nitric oxide [In Process Citation]. J Soc Gynecol Investig 1999;6:120-6.
4. Fujii EY, Takahashi N, Kodama Y, Roman C, Ferriero DM, Parer JT. Hemodynamic changes during complete umbilical cord occlusion in fetal sheep related to hippocampal neuronal damage. Am J Obstet Gynecol 2003;188:413-8.
5. Rossiter JP, Anderson LL, Yang F, Cole GM. Caspase-3 activation and caspase-like proteolytic activity in human perinatal hypoxic-ischemic brain injury. Acta Neuropathol 2002;103:66-73.
6. van Landeghem FK, Felderhoff-Mueser U, Moysich A, et al. Fas (CD95/Apo-1)/Fas ligand expression in neonates with pontosubicular neuron necrosis. Pediatr Res 2002;51:129-35.
7. Stadelman C, Mews I, Srinivasan A, Deckwerth TL, Lassmann H, Bruck W. Expression of cell death-associated proteins in neuronal apoptosis associated with pontosubicular neuron necrosis. Brain Pathol 2001;11:273-81.
8. Takizawa Y, Takashima S, Itoh M. A histopathological study of premature and mature infants with pontosubicular neuron necrosis: neuronal cell death in perinatal brain damage. Brain Res 2006;1095:200-6.
9. Mito T, Kamei A, Takashima S, Becker LE. Clinicopathological study of pontosubicular necrosis. Neuropediatrics 1993;24:204-7.
10. Grafe MR, Kinney HC. Neuropathology associated with stillbirth. Semin Perinatol 2002;26:83-8.
11. Ahdab-Barmada M, Moossy J, Painter M. Pontosubicular necrosis and hyperoxemia. Pediatrics 1980;66:840-7.
12. Bilkey DK. Neuroscience. In the place space. Science 2004;305:1245-6.
13. Dicks D, Myers RE, Kling A. Uncus and amiygdala lesions: effects on social behavior in the free-ranging rhesus monkey. Science 1969;165:69-71.
14. Scott BA, Avidan MS, Crowder CM. Regulation of hypoxic death in C. elegans by the insulin/IGF receptor homolog DAF-2. Science 2002;296:2388-91.

 

This is another segment of a chapter. I hope it usefully shares some of my experience looking at this entity under the microscope.

Dr. Peilin Zhang has submitted some interesting comments to this blog. Dr. Zhang suggests that we try to evaluate the early stages of trophoblast remodeling by measuring smooth muscle antigens from damaged media in maternal blood.

He also suggests that we try to pool pregnancy information on patients with the genetic defect, MonoMac or Emberger’s syndrome in which NK cells, monocytes and B-cells are absent or low due to GATA2 mutations.

Thank you Dr. Zhang!

Go to the end of the Spiral Artery page to see his comments.