Abnormal blood-brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI
S P Cramer1, H Simonsen2, J L Frederiksen3
1Functional Imaging Unit, Dept. of Diagnostics, Glostrup Hospital, University of Copenhagen, Denmark ; Dept. of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.
Objectives:
To investigate whether blood-brain barrier (BBB) permeability is disrupted in normal appearing white matter in MS patients, when compared to healthy controls and whether it is correlated with MS clinical characteristics.
Methods:
Dynamic contrast-enhanced MRI was used to measure BBB permeability in 27 patients with MS and compared to 24 matched healthy controls.
Results:
Permeability measured as K(trans) was significantly higher in periventricular normal appearing white matter (NAWM) and thalamic gray matter in MS patients when compared to healthy controls, with periventricular NAWM showing the most pronounced difference. Recent relapse coincided with significantly higher permeability in periventricular NAWM, thalamic gray matter, and MS lesions. Immunomodulatory treatment and recent relapse were significant predictors of permeability in MS lesions and periventricular NAWM. Our results suggest that after an MS relapse permeability gradually decreases, possibly an effect of immunomodulatory treatment.
Conclusions:
Our results emphasize the importance of BBB pathology in MS, which we find to be most prominent in the periventricular NAWM, an area prone to development of MS lesions. Both the facts that recent relapse appears to cause widespread BBB disruption and that immunomodulatory treatment seems to attenuate this effect indicate that BBB permeability is intricately linked to the presence of MS relapse activity. This may reveal further insights into the pathophysiology of MS.
Insights
Blood-brain barrier (BBB) permeability is increased in normal-appearing white matter in multiple sclerosis (MS) patients, particularly during relapse. Immunomodulatory treatment may reduce this BBB disruption in MS.
Area of Science:
- Neuroimmunology
- Neuroimaging
- Neurology
Background:
- Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- The integrity of the blood-brain barrier (BBB) is crucial for brain function and its disruption is implicated in MS pathogenesis.
Purpose of the Study:
- To investigate blood-brain barrier (BBB) permeability in normal-appearing white matter (NAWM) in MS patients compared to healthy controls.
- To determine the correlation between BBB permeability and MS clinical characteristics, including relapse activity and treatment.
Main Methods:
- Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was employed to quantify BBB permeability.
- The study included 27 patients with MS and 24 matched healthy controls.
Main Results:
- Significantly higher BBB permeability (Ktrans) was observed in periventricular NAWM and thalamic gray matter of MS patients versus controls.
- Periventricular NAWM showed the most substantial difference in permeability.
- Recent relapse was associated with increased permeability in NAWM, thalamic gray matter, and MS lesions.
- Immunomodulatory treatment and recent relapse were significant predictors of permeability.
Conclusions:
- BBB pathology is a critical component of MS, most evident in periventricular NAWM.
- Recent MS relapse leads to widespread BBB disruption, which may be attenuated by immunomodulatory treatment.
- BBB permeability is closely linked to MS relapse activity, offering insights into MS pathophysiology.
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