What causes white matter in the brain?

What Causes White Matter in the Brain

White matter in the brain is primarily composed of myelinated axonal fibers extending from neuronal cell bodies, along with supporting glial cells such as oligodendrocytes, oligodendrocyte precursor cells, astrocytes, and microglia. 1

Composition and Structure of White Matter

• White matter gets its distinctive appearance from the concentrated myelinated axonal fibers that extend from neuronal soma (cell bodies) located in the gray matter 1
• The white color is due to myelin, a fatty substance that forms sheaths around axons, providing insulation and allowing for faster signal transmission 1, 2
• Supporting cells in white matter include oligodendrocytes (which produce myelin), oligodendrocyte precursor cells, astrocytes, and microglia 1
• Microglia are particularly abundant in cerebral white matter and play a crucial role in maintaining axon-glia integrity 2

Development and Maintenance of White Matter

• Myelination is a dynamic process that begins during fetal development and continues well into adulthood 2
• During brain development, oligodendrocytes wrap layers of myelin around axons, creating the white matter tracts 1
• The contrast between white and gray matter changes throughout development due to ongoing myelination 2
• In infants and young children, contrast between cortex and white matter is maximal before myelination begins 2
• During active myelination, this contrast transiently diminishes, creating a "T2 isointense" stage usually at 8-12 months of age 2
• Cortical thickness progressively increases during myelination 2

White Matter Changes Throughout Life

• Males have approximately 176,000 km of myelinated fibers at age 20, decreasing to 97,200 km by age 80 3
• Females have approximately 149,000 km of myelinated fibers at age 20, decreasing to 82,000 km by age 80 3
• This represents a significant 10% decrease per decade or a total decrease of 45% from age 20 to 80 years 3
• The loss primarily affects thinner myelinated fibers, with relative preservation of thicker ones 3
• This age-related decline in white matter volume and integrity may contribute to cognitive decline in elderly individuals 3

White Matter Pathology

• White matter abnormalities are associated with numerous neurological diseases 1
• CSF1R gene mutations can lead to primary microgliopathy that disrupts axon-glia integrity, causing white matter lesions 2
• White matter lesions in CSF1R-related leukoencephalopathy typically occur without contrast enhancement and have a predilection for frontal and parietal lobes 2
• Pathological examination of affected white matter often reveals demyelination, vacuolization of myelin, axonal spheroids, gliosis, lipid-laden macrophages, and widespread microglial activation 2
• Diffusion restriction in white matter can be a sign of fluid trapped between degenerating layers of myelin sheets 2
• White matter calcifications can occur in various conditions, including CSF1R-related leukoencephalopathy, often in a "stepping-stone pattern" or as "spotty calcifications" 4

Imaging of White Matter

• MRI is the preferred imaging method for evaluating white matter due to its optimal delineation of gray and white matter structures 2
• T2-weighted and FLAIR sequences are particularly useful for identifying white matter abnormalities 2
• Diffusion tensor imaging is important for inspecting the microscopic architecture of white matter and identifying possible axonal pathfinding disorders 2
• Susceptibility-weighted imaging (SWI) can help characterize calcifications in white matter 4
• FDG-PET may show glucose hypometabolism in white matter tracts affected by disease 2

Clinical Significance of White Matter

• White matter degeneration is associated with cognitive impairment, particularly affecting visuospatial processing, processing speed, language, and recognition memory 5
• White matter abnormalities can manifest as "Dark White Matter" (DWM) on T2/FLAIR imaging in conditions like non-ketotic hyperglycemic hyperosmolar state and encephalitis 6
• The loss of white matter integrity after stroke can persist for years and is associated with poststroke cognitive impairment 5
• White matter dysfunction is increasingly recognized as a contributor to neurodegenerative disorders affecting cognition 5

Understanding the causes and composition of white matter is essential for diagnosing and treating various neurological conditions that affect white matter integrity.