The gray matter remains normal in all characteristics while the white matter changes texture, becoming soft and gelatinous. Rarefaction of the white matter is seen through light microscopy and the small number of axons and U-fibers that were affected can also be seen. Numerous small cavities in the white matter are also apparent. The key characteristic that sets VWM apart from the other leukodystrophies is the presence of foamy oligodendrocytes. These foamy oligodendrocytes tend to have increased cytoplasmic structures, a greater number of irregular mitochondria and a higher rate of apoptosis. Abnormally shaped astrocytes with fibrile infections are very prevalent throughout the capillaries in the brain. Strangely, astrocytes are affected more than oligodendrocytes; there is even a reduction in the astrocyte progenitors, yet axons remain relatively unharmed. Diagnosis
Most diagnosis occurs in the early years of life around 2 to 6 years old. There have been cases in which onset and diagnosis have occurred late into adulthood. Those with onset at this time have different signs, particularly the lack of cognitive deterioration. Overall, detection of adult forms of VWM is difficult as MRI was not a common tool when they were diagnosed. Common signs to look for include chronic progressive neurological deterioration with cerebellar ataxia, spasticity, mental decline, decline of vision, mild epilepsy, hand tremor, the ability to chew and swallow food becomes difficult, rapid deterioration and fibrile infections following head trauma or fright, loss of motor functions, irritability, behavioural changes, vomiting, and even coma.
This mutation has also been documented in rodents, but they do not acquire VWM, while humans do. Another common mutation is G584A found in the eIF2B5 subunit. A correlation with stress has also been made, as eIF2B plays a central role in stress management – it is essential in down regulation protein synthesis in different stress conditions – and VWM patients are highly sensitive to stress. Protein eIF2B exists in all cells, and if this protein is reduced enough the cell will be negatively affected, and if it is reduced to zero, the cell will die. In affected cells, the protein is reduced to about 50%, which is acceptable for functionality in most cells, but not in glial cells since they synthesize a large amount of proteins constantly and need as many functioning proteins within them as possible. This would lower the baseline of the amount of stress a cell can handle, and thus in a stressed environment, it would have detrimental effects on these cells. Mutations in three of the subunits of eIF2B (2,4,&5) has been seen in both VWM and premature ovarian failure. The North American Cree population has also been found to have a distinctive mutation, R195H, which can lead to VWM. All patients who have been studied only have one mutation present in the gene, causing the eIF2B to still be active, which leads to VWM. If two mutations occurred, then eIF2B activity would be stopped by the body. Neuropathology
Upon autopsy, the full effect of VWM has been documented.