Picture of multiple sclerosis imaging

A Graphic Look at Multiple Sclerosis—Part 2

#Atrophy #Imaging #Lesions

Driven by 2 distinct pathologies, multiple sclerosis (MS) is a chronic, debilitating autoimmune disorder that can cause extensive damage to the central nervous system (CNS) over time. The 2 unique types of disease activity seen in patients with MS are White Matter (WM) pathology and Grey Matter (GM) pathology.1-4 Historically, researchers and clinicians focused on WM activity, yet recent evidence has made it clear that GM damage is also critically important and a major cause of disease disability.5-8

Both WM and GM pathologies are characterized by lesions in the brain and spinal cord that can cause a range of debilitating symptoms.9 This overview will focus on the differences between these 2 types of lesions and the symptoms associated with each.


The graphic below provides a quick overview of some of the differences and similarities between WM pathology and GM pathology in multiple sclerosis.


What are some key features of the lesions?

Icon of a white matter lesion
Larger and highly inflammatory3,4,10,11
Icon of a grey matter lesion
Smaller minimally inflammatory3,4,10,11

Up to 13x more lymphocyte
infiltration in WM lesions10

Icon showing that lesions in white matter disrupt the Blood-Brain Barrier (BBB)
Disrupts blood-brain barrier (BBB)3,10
Icon showing that lesions in grey matter do not significantly disrupt the Blood-Brain Barrier (BBB)
No significant disruption of BBB3,10
Icon showing white matter lesions are easy to detect on MRI
Easy to detect on magnetic resonance imaging (MRI)12,13
Icon showing that grey matter lesions are difficult to detect on MRI
Difficult to detect on MRI12-14

While WM and GM lesions can both cause significant damage to nerve tissue and trigger debilitating symptoms, there are important pathological differences between the 2 types of lesions. WM lesions cause significant disruption of the BBB, substantial infiltration of T cells into the CNS, and significant amounts of complement deposition.3,9,10 As a result, WM lesions are highly inflammatory, which is one of their defining characteristics. However, with GM lesions, there is a general absence of lymphocytes with minimal infiltration of T cells.3,9,10 In addition, there are no significant BBB disruption, no complement deposition, and minimal inflammation.3,9,10 Finally, GM lesions are usually smaller in size than WM lesions, which is part of what makes them harder to detect using MRI.11

In a 2001 study of cortical lesions, researchers found that WM lesions contain 13 times more lymphocytes than cortical lesions and 6 times more microglia and macrophages, indicating there is a very different mechanism driving the tissue damage found in GM tissue.10

Where are lesions most commonly found?

White Matter Pathology15,16

Icons showing white matter pathology
Periventricular region
Icons showing white matter pathology
Juxtacortical areas
Icons showing white matter pathology
Brain stem
Icons showing white matter pathology
Spinal cord

Grey Matter Pathology12,17

Cortical Grey Lesions

Icons showing grey matter pathology
Temporal lobe
Icons showing grey matter pathology
Frontal lobe

Deep Grey Matter Lesions

Icons showing deep grey matter lesions
Icons showing deep grey matter lesions
Basal ganglia
Icons showing deep grey matter lesions

WM lesions have been detected in a range of locations, but they are most commonly found in a few key areas, including the brain stem, the spinal cord, and the periventricular region (near one of the 4 ventricles of the brain).15,16,18 WM lesions are also commonly found in juxtacortical areas (WM areas adjacent to the GM of the cortex).15 One of the best ways to visualize WM lesions with MRI technology is to use fluid-attenuated inversion recovery (FLAIR) sequences, which suppress signals from cerebrospinal fluid and allow for clearer imaging of WM tissue.15

While GM lesions have historically been difficult to detect, recent advances in MRI technology have improved our ability to visualize them.12,13 Two technologies that have been especially useful are double-inversion recovery (DIR) and phase-sensitive inversion recovery (PSIR) sequences.12 By using DIR and PSIR technologies, researchers have concluded that cortical lesions are mostly found in the frontal and temporal lobes of the brain.12,17 Below the cortex, in Deep Grey Matter structures, lesions are typically found in the thalamus (an important relay center), basal ganglia (including the caudate, putamen, and globus pallidus), hypothalamus (a structure that helps control metabolic and endocrine functions), hippocampus (involved in memory and the olfactory bulb), and the cerebellum (which regulates motor movements).17,19


What symptoms are commonly associated with lesions?

White Matter Symptoms9

Icons showing white matter symptoms
Physical disability
Icons showing white matter symptoms
Visual disturbances
Icons showing white matter symptoms
Sensory deficits
Icons showing white matter symptoms
Bowel and bladder dysfunction

Grey Matter Symptoms12

Icons showing grey matter symptoms
Physical disability
Icons showing grey matter symptoms
Cognitive impairment
Icons showing grey matter symptoms
Painful syndromes
Icons showing grey matter symptoms

Both WM and GM lesions have been associated with neurological symptoms, some of which can dramatically impact a patient’s quality of life.9,12,20 The type of symptom that the patient experiences is dependent on where the lesion is located. For instance, WM lesions on the optic nerve or within WM tracts of the left frontal lobe can cause patients to experience visual dysfunction—a symptom commonly associated with WM lesions.9 Other symptoms commonly connected with WM lesions include physical disability, sensory deficits, and bowel and bladder dysfunction.9

With GM symptoms, the location of the lesion is also important. For instance, lesions located in the hippocampus and amygdala (2 Deep GM structures) are associated with cognitive impairment, a symptom commonly seen in patients with GM pathology.9 Some additional symptoms commonly associated with GM lesions include physical disability, painful syndromes, and fatigue.12

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