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Microscopic Findings

Any tissue processing produces artifacts that have to be interpreted: fixation procedures as well as staining techniques. The artifacts are dependent on the time periods between death and fixation, the duration of the fixation process, the temperatures, etc. For example the freezing process of (brain) tissue leads to crystalline vacuoles within the tissue sections (Fig. 4.26a, b).

Additionally, the forensic neuropathologist fundamentally needs to be able to reliably distinguish between vital and postmortem changes (cf. Oehmi-chen 1995). This requires among other things the testing and use of novel histochemical and immuno-histochemical staining techniques that can help to establish the length of the postmortem interval.

So-called dark neurons (Fig. 4.26c) can appear among otherwise normal neurons. Dark neurons are irregularly contoured, shrunken neurons that are created by excessive pressure on unfixed postmortem tissue (Scharrer 1938; Cammermeyer 1961, 1975). Apical dendrites also have a dark coloration, sometimes in combination with a corkscrew-like appearance. There is a danger of confusing dark neu rons with ischemic cell necrosis. In our own investigations (Oehmichen and Gencic 1980a) we could observe that most, but not all dark neurons have a potent albumin uptake, an indication that they represent lesions of neuronal metabolism (and/or membrane).

Animal experiments demonstrate that the following three types of altered neurons appear at different postmortem intervals in rats (Oehmichen and Gencic 1980b):

1. Shrunken, hyperchromatic neurons, whose number declines as the postmortem interval proceeds.

2. Swollen and autolytic neurons, with a pale peri-karyon and nucleoplasm, and an absence of Nissl bodies. The nucleus can no longer be differentiated from the vacuolized and autolysing cytoplasm. The cells themselves have lost their contours and appear swollen and spherical. The swelling in particular represents the most fundamental postmortem change (whose differential diagnosis is retrograde degeneration).

3. Pericellular spaces surrounding neurons may be caused by postmortem autolytic processes that mimic edema, especially in the gray matter.

Children two years old and younger almost invariably exhibit periventricular and perivenous accumulation of cytoplasm-poor, lymphocyte-like mononu-clear cells which suggest an encephalitis (so-called pseudoencephalitis). Those cell aggregations consist of neuroblasts as an indication of development, not of an inflammatory process. This age group also regularly shows a superficial granule layer of the cerebellar cortex composed of germinal cells (matrix cells). These usually disappear some time between the second and fourth years of life.

In cases of sudden death with brief agony or if tissues have been poorly fixed (Hirano 1981), extensive acute swelling of oligodendroglia is common. In addition, a generalized swelling and clasmatodendrosis of astrocytes is often seen. These changes are rather slight compared to the neuronal changes. They must also be regarded as non-specific and do not constitute markers of edema.

Lindenberg (1982) points out that the state of the brain before circulatory arrest also plays a role. If the agony was brief (healthy person who died within minutes), neurons and glial cells may show marked postmortem ischemic cell injury (vacuolation, ho-mogenization, acute shrinkage associated with nuclear changes). Agony of long duration results in a largely unchanged cytology.

Not only does the architecture of the cells change, but their functional state and/or stainability with various reagents changes as well. Postmortem function and staining are influenced by many factors in addition to fixation procedures (time, temperature,

Fig. 4.26a-c. Minsinterpretable findings. a, c Crystalline vacu- tissue; b dark neurons as a postmortem phenomenon (a-c H&E; oles as seen within tissue sections after freezing of native brain magnification a x50, b X300, c X500)

and type of procedure). It is further known that the enzyme activity of cells and tissue depends in large part on the length of the postmortem interval (for a survey of findings prior to 1980 see Oehmichen 1980).

Numerous variables are known to affect the immunoreactivity of cells and tissue in the antigen-antibody reaction for immunohistologi-cal demonstration of epitopes (Grizzle et al. 2001). Among these variables are the interval between cellular death and fixation as well as the duration of fixation, the method of tissue processing, the preparation of paraffin blocks, the method of attaching tissue sections to microscopic slides, the interval between cutting tissue sections and immunostain-ing. To summarize, once findings are obtained by performing the relevant investigations, their proper interpretation requires long experience in the routine practice of neuropathology.


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