What are the clinical differences between white matter and grey matter lesions?

From the Guidelines

White matter and gray matter lesions present with distinct clinical manifestations due to their different locations and functions in the brain, with white matter lesions typically causing disconnection syndromes and gray matter lesions affecting neuronal cell bodies and causing focal neurological deficits. The clinical differences between these two types of lesions are crucial in determining the underlying cause of neurological symptoms. White matter lesions, which contain myelinated axons that transmit signals between brain regions, often cause deficits in motor function, sensation, and coordination, presenting with symptoms such as weakness, numbness, ataxia, visual field defects, or cognitive slowing 1. In contrast, gray matter lesions, which affect neuronal cell bodies, typically cause focal neurological deficits related to the specific function of the affected area, including seizures, aphasia, memory problems, behavioral changes, or movement disorders.

Key Differences in Clinical Manifestations

• White matter lesions: disconnection syndromes, gradual progressive symptoms, multifocal lesions suggesting demyelinating diseases like multiple sclerosis
• Gray matter lesions: focal neurological deficits, abrupt dramatic presentations, cortical lesions indicating stroke, encephalitis, or neurodegenerative conditions

The distribution pattern of lesions also matters, with multifocal white matter lesions suggesting demyelinating diseases like multiple sclerosis, while cortical gray matter lesions may indicate stroke, encephalitis, or neurodegenerative conditions 1. Understanding these differences helps clinicians narrow their differential diagnosis and direct appropriate testing when evaluating patients with neurological symptoms. Advanced MRI techniques, such as double inversion recovery and phase-sensitive inversion recovery, can be used to detect and interpret cortical gray matter lesions, but standardization of these methods is needed 1.

Diagnostic Considerations

• Use of T2-FLAIR sequences to detect periventricular lesions and juxtacortical lesions
• Importance of lesion morphology and distribution pattern in determining the underlying cause of neurological symptoms
• Role of advanced MRI techniques in detecting and interpreting cortical gray matter lesions

In clinical practice, it is essential to consider the clinical differences between white matter and gray matter lesions to provide accurate diagnosis and treatment. The most recent and highest quality study 1 emphasizes the importance of understanding these differences in determining the underlying cause of neurological symptoms and directing appropriate testing. By recognizing the distinct clinical manifestations of white matter and gray matter lesions, clinicians can improve patient outcomes and quality of life.

From the Research

Clinical Differences Between White Matter and Grey Matter Lesions

The clinical differences between white matter and grey matter lesions are significant in the context of multiple sclerosis (MS) and other neurological disorders.

• White matter lesions are defining characteristics of MS, whereas grey matter involvement is a less recognized attribute 2.
• Grey matter atrophy is closely correlated to clinical disability, and recent investigations have made it possible to depict cortical lesions and estimate grey matter atrophy using various methods 2.
• Normal-appearing white matter is far from normal in MS, with abnormalities in normal-appearing white matter contributing to the risk of autoimmune acute demyelination 3.
• The spatial distribution of normal-appearing white matter abnormalities in persons with MS largely recapitulates the anatomical distribution of probabilities of T2 hyperintense lesions 3.

Pathophysiology of White Matter Lesions

• Cerebral white matter lesions represent a spectrum of age-related structural changes that are identified as areas of white matter high signal intensity on brain magnetic resonance imaging (MRI) 4.
• The cerebrovascular and glymphatic systems play a crucial role in preserving white matter integrity, and damage to these systems can lead to the disruption of cerebral autoregulation and the accumulation of metabolic waste products 4.
• White matter lesions are particularly vulnerable to hypoxic, inflammatory, and metabolic insults, making them the first recognized pathologies of neurovascular-glymphatic dysfunction 4.

Relationship Between White Matter Lesions and Grey Matter Atrophy

• There is a significant relationship between white matter lesions and grey matter atrophy in MS, with higher white matter lesion volumes associated with lower grey matter volumes or lower cortical thicknesses 5.
• The most consistent relationship between white matter lesions and grey matter atrophy is seen in early (relapsing) disease, suggesting that grey matter neurodegeneration is mostly secondary to damage in the white matter during early disease stages 5.
• In progressive MS, grey matter neurodegeneration becomes more detached and dominated by other, possibly primary neurodegenerative disease mechanisms 5.