From the Guidelines
Diffuse white matter degradation on MRI is most commonly caused by conditions such as multiple sclerosis, age-related small vessel disease, and progressive multifocal leukoencephalopathy, which can lead to significant morbidity and mortality if not properly managed. The causes of diffuse white matter degradation on MRI can be diverse, including immune-mediated demyelination, chronic ischemia, toxic-metabolic disorders, infectious processes, genetic disorders, radiation therapy, and chronic hypoxic conditions 1.
Common Causes
- Multiple sclerosis: involves immune-mediated demyelination, leading to focal or diffuse white matter lesions 1
- Age-related small vessel disease: chronic ischemia damages white matter, resulting in diffuse or focal lesions 1
- Progressive multifocal leukoencephalopathy: a rare and often fatal viral disease caused by the JC virus, leading to diffuse white matter degradation 1
- Leukodystrophies: genetic disorders affecting myelin, resulting in progressive white matter damage 1
- Toxic-metabolic disorders: certain medications, alcohol abuse, or nutritional deficiencies can cause demyelination and white matter damage 1
Diagnostic Considerations
It is essential to note that white matter lesions and brain atrophy are highly unspecific MRI features, and common mimics of CSF1R-related leukoencephalopathy include diseases with predominant white matter involvement, such as multiple sclerosis, cerebral vasculitis, or cerebral autosomal dominant/recessive arteriopathy with subcortical infarcts and leukoencephalopathy 1. Early identification of the underlying cause is crucial for appropriate management and potentially slowing disease progression. Nuclear medicine imaging modalities, such as FDG-PET or brain SPECT scans, may also be helpful in the diagnostic workup of suspected CSF1R-related leukoencephalopathy cases 1.
From the Research
Causes of Diffuse White Matter Degradation on MRI
The causes of diffuse white matter degradation on MRI can be attributed to various factors, including:
- Demyelinating disorders such as multiple sclerosis, tumefactive demyelinating lesions, and acute disseminated encephalomyelitis 2
- Infectious processes like Lyme disease, progressive multifocal leukoencephalopathy, and human immunodeficiency virus (HIV) encephalopathy 2
- Vascular processes including small-vessel disease, arteriolosclerosis, and cerebral amyloid angiopathy 2, 3
- Toxic-metabolic processes such as osmotic myelinolysis, methotrexate leukoencephalopathy, and posterior reversible encephalopathy syndrome 2
Disease-Specific Causes
Specific diseases can also cause diffuse white matter degradation on MRI, including:
- Multiple sclerosis, which can lead to diffusely abnormal white matter (DAWM) with poorly defined boundaries and signal intensity between normal-appearing white matter and classic lesions 4
- Cerebral small vessel diseases (SVDs), which can cause white matter hyperintensities (WMHs) on T2-weighted images due to chronic hypoperfusion, impaired cerebrovascular reactivity, or blood-brain barrier leakage 3
- Relapsing-remitting multiple sclerosis, which can result in microstructural white matter changes related to diffuse demyelination, edema, and increased fiber density and complexity 5
Imaging Findings
Imaging findings for diffuse white matter degradation on MRI can vary widely, including:
- Small multifocal white matter lesions to confluent or extensive white matter involvement 2
- Diffuse abnormal white matter with poorly defined boundaries and signal intensity between normal-appearing white matter and classic lesions 4
- White matter hyperintensities (WMHs) on T2-weighted images due to chronic hypoperfusion, impaired cerebrovascular reactivity, or blood-brain barrier leakage 3
- Microstructural white matter changes related to diffuse demyelination, edema, and increased fiber density and complexity 5