Allergic encephalomyelitis and allergic peripheral neuritis, progressive multifocal leukoencephalopy (PML) and the white matter involvement in Subacute Progessive Panencephalitis (SSPE) are other examples of human demyelinating diseases. Some of these are due to an immune mediated attack on myelin, others require viral infection of oligodendroglia-with or without immune mediated oligo lysis for myelin destruction. You should think about this interesting group of human diseases and about the animal model which has been used extensively to study demyelination, experimental allergic encephalomyelitis. By convention metabolic disorders in which myelin breakdown and or failed maintance result in myelin loss, are considered leukodystrophies. An example will be discussed under neonatal and pediatric neuropathology.

We will look at a few examples of white matter lesions which fall within the demyelinating category and illustrate some of these points. We begin with acute hemorrhagic leucoencephalitis ( Hurst's Disease) which many authors feel represents a hyper acute form of post infectious encephalomyelitis. Fuel for this supposition is found in cases of typical post infectious encephalomyelitis which contain microscopic areas with the features of acute hemorrhagic leucoencephalitis. As in post infectious encephalomyelitis, the onset of acute hemorrhagic leucoencephalitis is often preceded by a systemic infection. Typical gross findings in individuals who die during the acute illness are depicted in photograph AHLa, below, which illustrates multifocal small hemorrhages throughout the cerebral white matter. Such lesions may be seen throughout the brain including the brain stem. Microscopic findings include the images in AHLb and c. Note small ball shaped hemorrhages around necrotic microvessels in "a" and perivenular predominantly neutrophilic infiltrates in "b'.

Photographs AHLa,b and c

The next few photographs depict perivenular findings which are typical in post infectious (a, b and c) and post rabies vaccination allergic encephalomyelitis (d). In "EM a and b" note the perivenular areas of demyelination in two sections stained with different myelin stains. Such lesions exhibit perivenular inflammatory infiltrates composed predominantly of lymphocytes and and macrophages. A typical infiltrate is seen in EM c. Based in part, upon similarities with experimental allergic encephalitis and the failure to identify a pathogen within involved neural tissues, post infectious encephalomyelitis is presumed to be an "allergic" immune mediated process.

Photographs EM a,b and c

The last pictures, "EM d and e", in this series are of a spinal cord section taken from a patient who suffered post vaccination allergic encephalomyelitis following immunization with rabies vaccine. This case occurred earlier in this century when nervous system or duck embryo vaccines were utilized. This complication of rabies vaccination does not occur following vaccination with modern human diploid cell vaccines which are free of neural antigens. Note the large confluent areas of demyelination in "d" and the perivascular round cell infiltrate within the demyelinated area in "e".

Photographs EM d and e

The last set of photographs depict central nervous system demyelination with is the direct result of oligodendroglial lysis by a virus, the JC papova virus. The disease, progressive multifocal leukoencephalopathy, PML, occurs in immunocompromised individuals. With the AIDS epidemic it has became a relatively common entity. Photographs "PML a, b, c and d" depict typical findings. In "a" note the multifocal areas of demyelination. In such lesions myelin removal is accomplished by macrophages. Surviving oligodendroglia exhibit large viral intra nuclear inclusion bodies, visualized in "b" an H&E stained section, and in "c" an in-situ hybridization demonstrating JC viral nucleic acid. Astrocytes often are bizarre, with large hyperchromatic nuclei as seen in last photo of this series "d".

Photographs PMLa,b,c and d