Helle Juhl Simonsen

Abnormal blood-brain barrier permeability in normal appearing white matter in multiple sclerosis investigated by MRI

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 Ktrans 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.

Corticospinal tract degeneration and possible pathogenesis in ALS evaluated by MR diffusion tensor imaging

BACKGROUND: MR diffusion tensor imaging (DTI) appears to be a powerful method to investigate the neuronal and axonal fibre distribution in the human brain. Changes in diffusion characteristics of water molecules in the white matter can be estimated as the apparent diffusion coefficient (ADC) and the fractional anisotropy index (FA). OBJECTIVES: To characterize DTI changes at three different levels in the corticospinal tract (CST) (corona radiata, internal capsule and pons) in order to elucidate if pathogenesis of ALS is due to an anterograde or retrograde axonal degeneration. METHODS: We studied eight ALS patients with clinical signs of upper motor neuron involvement. The patients were compared with 11 healthy age‐matched controls. RESULTS: ADC was significantly increased in the CST in ALS patients at the level of the internal capsule and also increased in the pons, but without statistical significance. ADC was unchanged at the level of the corona radiata. FA was significantly reduced at the lowest level (pons), only tended to be reduced in the internal capsule, but was also unchanged in the corona radiata. CONCLUSIONS: Segmentation of the CST into three regions supports the hypothesis of a ‘dying back’ mechanism in ALS and suggests that ADC is a more sensitive measure than FA to detect pathological changes in ALS.

Permeability of the blood–brain barrier predicts conversion from optic neuritis to multiple sclerosis

See Naismith and Cross (doi:10.1093/brain/awv196) for a scientific commentary on this article.  Optic neuritis is highly associated with development of multiple sclerosis. Cramer et al. show that MRI measures of blood-brain barrier permeability improve prediction of conversion to multiple sclerosis within 2 years, compared to T2-lesion count alone. Permeability measures also correlate with CSF biomarkers of cellular trafficking and blood-brain barrier breakdown.

Permeability of the blood–brain barrier predicts no evidence of disease activity at 2 years after natalizumab or fingolimod treatment in relapsing–remitting multiple sclerosis

To investigate whether blood–brain barrier (BBB) permeability, as measured by dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI), can provide early detection of suboptimal treatment response in relapsing–remitting multiple sclerosis (RRMS).