Primary demyelination

A number of animal diseases caused by viruses involve primary demyelination and often are associated with inflammation 641... 

A number of animal diseases caused by viruses involve primary demyelination and often are associated with inflammation. These diseases are studied as animal models, which may provide clues about how a viral infection could lead to immune-mediated demyelination in humans [1, 5, 6]. Canine distemper virus causes a demyelinating disease, and the lesions in dog brain show a strong inflammatory response with some similarities to acute disseminated encephalomyelitis in man [ 1 ]. Visna is a slowly progressive demyelinating disease of sheep caused by a retrovirus [ 1 ]. 

MS lesions or plaques can be identified grossly at autopsy (Fig. 38-1) and are sharply demarcated from the surrounding tissue. Plaques occur throughout the white matter, but areas of predilection such as the periventricular white matter are well known. Microscopic examination characteristically shows loss of myelin with preservation of axons (primary demyelination). However, although the most prominent pathology in MS is demye-lination, there are recent indications also for axonal and cortical pathology. Now techniques of confocal microscopy and immunocytochemistry have clearly demonstrated that transected axons are common in MS lesions [9],... 

Primary Demyelination and Hypomyelination in the PNS Charcot-Marie Tooth Diseases (CMT)... 

CMT diseases are the most frequent hereditary sensory-motor neuropathies. They are distinguished from other types of genetic neuropathies, either purely motor, mainly distal and dysautonomous neuropathies which mainly alter sensory and sympathetic fibers of the peripheral nerves. We only deal here with CMT diseases and among the many genetic causes, those that give rise to primary demyelinating diseases of the peripheral nervous system (PNS). 

The most common cause of primary demyelination is MS, so demyelinating optic neuropathy is often associated with MS. Other conditions have been implicated in demyelinating optic neuropathy, including acute transverse myelitis, acute disseminated encephalomyelitis, herpes zoster, Gnillain-Barre syndrome, Devic s nemomyelitis optica, Epstein-Barr virus, Charcot-Marie-Tooth syndrome, and chronic multifocal demyelinating nemopathy. 

Mason JL, Ye P, Suzuki K, D Ercole AJ, Matsushima GK (2000) Iiisuliii-like growdi factor-1 inhibits mature oligodendrocyte apoptosis duiing primary demyelination. J Neurosci 20 5703—5708. 

Optic neuropathy (axonal degeneration, primary demyelination) extrapyramidal syndrome (necrosis of putamen) retinopathy (edema)... 

Chiang, C.-S., Powell, H. C., Gold, L. H., Samini, A., and Campbel, I. L., Macro-phage/microghal-mediated primary demyelination and motor disease induced by the central nervous system production of interleukin-3 in transgenic mice, J. Clin. Invest., 97, 1512, 1996. 

Primary demyelination affects only the myelin. Primary demyelinating lesions are characterized histologically by destruction of myelin and by abundant foamy KPl-positive macrophages containing myelin debris and lipid droplets. Within the lesion, NF-positive axons are spared (Fig. 20.60). In longitudinal sections of white matter, parallel NF-positive axons are straight and long. 

FIGURE 20.60 Primary demyelination with preservation of brown NF-positive axons. Some axons are swollen and are called spheroids. Lipid-laden macrophages and gliosis are not stained brown in this section of this brain biopsy specimen, but their pale gray features are still evident. 

Secondary demyelination is the loss of myelin secondary to loss of axons. Axonal trophic factors sustain myelin. When the axon is severed or not sustained by its neuron of origin, the axon and then its myelin degenerates. This can happen secondary to infarcts, trauma, toxic, metabolic, or degenerative nervous system diseases. In contrast to primary demyelination, straight and long NF-positive axons are not seen in secondary demyelination. Acutely, the axons crumble into short pieces, and in a few days they are eaten by macrophages and disappear. NF stains thus distinguish secondary from primary demyelination. 

Reith KG, Di Chiro G, Cromwell LD, et al. Primary demyelinating disease simrrlating glioma of the corpus callosum. J Neurosurg. 1981 55 620-624. 

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