White matter pathology

A rare case of a reversible neurological disturbance associated with focal subcortical white matter pathology has been described after administration of methotrexate 3 g/m. In patients who received 8-12.5 g/m, the incidence of neurological abnormalities was 4%. All of these patients were also receiving methotrexate intrathe-cally as well, but the relevance of this is not known (28). 

According to Dyer et al., white matter pathology in untreated PKU is a developmental process, whereby elevated phenylalanine concentrations arrest the myelination causing reduced myeUn formadon and hypomyelination. In early treated patients, myelin lesions reflect demyelination or dysmyelination and represent loss or impairment of previously assembled myelin [50] (Box 9.5). 

The diffuse character of white matter pathology in PKU may compromised multiple pathways resulting in different deficits in motor skills, coordination, visual functioning, processing speed, language, manory and learning as well as attention and executive functioning [42]. 

Anderson PJ, Leuzzi V. White matter pathology in phenylketonuria. Mol Genet Metab. 2010 99 Suppl LS3-9. 

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],... 

The pathological effects seem to involve damage to the gray matter, and possibly the white matter, in the brain. 

The toxic effect is known as histotoxic hypoxia. Cyanide also directly stimulates chemoreceptors, causing hyperpnea. Lack of ATP will affect all cells, but heart muscle and brain are particularly susceptible. Therefore, cardiac arrythmias and other changes often occur, resulting in circulatory failure and delayed tissue ischemic anoxia. Death is usually due to respiratory arrest resulting from damage to the CNS, as the nerve cells of the respiratory control center are particularly sensitive to hypoxia. The susceptibility of the brain to pathological damage may reflect the lower concentration of cytochrome oxidase in white matter. 

Magaki et al. [2007] measured the levels of loosely bound, nonheme, and total iron and copper in the frontal cortex and hippocampus of patients with mild-moderate AD (n = 3), severe AD (n = 8), and dementia with Lewy bodies (DLB, n = 6). Additionally, the expression of iron regulatory protein 2 (IRP2) was examined in relation to the pathological hallmarks of AD, that is, 5 amyloid plaques, neurofibrillary tangles (NFT), and Lewy bodies. A significant decrease of loosely bound iron was found in the hippocampal white matter of both mild-moderate and severe AD patients and a trend toward increased... 

Winton M. J., Joyce S., Zhukareva V., Practico D., Perl D. P., Galasko D., Craig U., Trojanowski J. Q., and Lee V. M. (2006). Characterization of tau pathologies in gray and white matter of Guam parkinsonism-dementia complex. Acta Neuropathol. (Berl) 111 401 112. 

Metabolic information of infarcted tissue can be retrieved by selecting a single cuboid volume of the pathological area for the spectroscopic examination using one of the above described SVS spectroscopy sequences. Results from an SVS MRS examination at 1.5 T with the PRESS sequence applying a TE of 144 ms are shown in Fig. 11.2. As expected, the infarcted area shows lactate which is visible as two inverted peaks (doublet) around 1.33 ppm while the contralateral tissue exhibits the spectrum of a healthy white matter. To achieve sufficient S/N for quantifiable SVS data from a 3 ml volume (approximately 1.5x1.5x1.5 cm3), the data acquisition time will take approximately 4 min. This leads to a rather... 

Mezzapesa DM, Rocca MA, Pagani E, Comi G, Filippi M (2003) Evidence of subtle gray-matter pathologic changes in healthy elderly individuals with nonspecific white-matter hyperintensities. Arch Neurol 60 1109-1112... 

MS is an autoimmune disease that attacks the myelin sheath of oligodendrocytes around the neuronal axons. This allows the axonal cytoskeleton to be damaged, bringing about secondary axonal loss and persisting neurological dysfunction. The characteristic pathology is of a lesion or plaque in the CNS white matter, formed by inflammation and demyelination and these can be classified into active, chronic active, or chronic silent plaques [86]. 

Fujiwara H, Hirao K, Namiki C, Yamada M, Shimizu M, et al. 2007. Anterior cingulate pathology and social cognition in schizophrenia A study of gray matter, white matter and sulcal morphometry. Neuroimage 36 1236-1245. 

Three cases of toxic and progressive spongiform leukoencephalopathy have also been reported as a result of vapor inhalation of heroin (21). There were generalized white matter abnormalities and pathology in the cerebellum, internal capsule, corpus callosum, and brain stem. 

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