Friday, 25 November 2016

#ClinicSpeak & #BrainHealth: I love my brain can you help?

Lesion load and brain volume loss correlates with cognitive impairment. #ClinicSpeak #BrainHealth #MSBlog #LoveYourBrain

I have taken a lot of flak about rebranding MS a preventable dementia; why? 


The study below clearly shows, and supports many other studies, that pwMS who have a high lesion load and reduced brain volume are more likely to be cognitively impaired. Are you surprised? Lesion volume (white dots) on MRI is an integrator of inflammation; the higher the lesion load the more inflammation you have had in the past. In comparison, brain volume is an integrator of end-organ damage and is a marker of how many neurons you have lost. Inflammation, the immunological shredder, damages and destroys nerves. This is why switching off inflammation in MS is strongly associated with a reduction in the rate of neuronal loss.  

If I had MS I would not want to have any new lesions and I would want a normal sized brain that did not shrink faster than normal. The latter is what we are trying to promote as a treatment target; treat-2-target of NEDA.  

It is time for pwMS to become activated and to ask their HCPs; do I have any ongoing inflammation on my MRI? If yes, you may want to push for a change in treatment. What about brain atrophy? How much end-organ damage have you acquired? The problem with that is that at present the measurement tools for brain volume change over time are not that reliable on an individual patient basis unless there is large amounts of atrophy. As I say this, I think this is a technological challenge and will be sorted out in the future. Another marker that may be better to measure is spinal fluid neurofilament levels; a marker of ongoing neuronal damage. The treatment aim is to normalise CSF neurofilament light levels, i.e. to prevent ongoing neuronal loss. If you love your brain you may just want to know about your spinal fluid neurofilament levels. 


It is not all bad news. With my rose-tinted glasses on it is clear that the more effective DMTs are much better at suppressing all inflammatory disease activity and slowing, and is some cases normalising, brain atrophy rates. 

Uher et al.  Identification of multiple sclerosis patients at highest risk of cognitive impairment using an integrated brain magnetic resonance imaging assessment approach. Eur J Neurol. 2016 Nov 22. doi: 10.1111/ene.13200.

BACKGROUND AND PURPOSE: While impaired cognitive performance is common in multiple sclerosis (MS), it has been largely underdiagnosed. Here a magnetic resonance imaging (MRI) screening algorithm is proposed to identify patients at highest risk of cognitive impairment. The objective was to examine whether assessment of lesion burden together with whole brain atrophy on MRI improves our ability to identify cognitively impaired MS patients.


METHODS: Of the 1253 patients enrolled in the study, 1052 patients with all cognitive, volumetric MRI and clinical data available were included in the analysis. Brain MRI and neuropsychological assessment with the Brief International Cognitive Assessment for Multiple Sclerosis were performed. Multivariable logistic regression and individual prediction analysis were used to investigate the associations between MRI markers and cognitive impairment. The results of the primary analysis were validated at two subsequent time points (months 12 and 24).

RESULTS: The prevalence of cognitive impairment was greater in patients with low brain parenchymal fraction (BPF) (<0.85) and high T2 lesion volume (T2-LV) (>3.5 ml) than in patients with high BPF (>0.85) and low T2-LV (<3.5 ml), with an odds ratio (OR) of 6.5 (95% CI 4.4-9.5). Low BPF together with high T2-LV identified in 270 (25.7%) patients predicted cognitive impairment with 83% specificity, 82% negative predictive value, 51% sensitivity and 75% overall accuracy. The risk of confirmed cognitive decline over the follow-up was greater in patients with high T2-LV (OR 2.1; 95% CI 1.1-3.8) and low BPF (OR 2.6; 95% CI 1.4-4.7).

CONCLUSIONS: The integrated MRI assessment of lesion burden and brain atrophy may improve the stratification of MS patients who may benefit from cognitive assessment.

2 comments:

  1. Can anyone ask their NHS neurologist for a lumbar puncture to check their neurofilaments and the OCBs after diagnosis?

    You mentioned that inactive lesions show inflammation which occurred in the past. What does it mean for the future? Are these neurons pre-programmed to get lost?

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    1. RE: "Can anyone ask their NHS neurologist for a lumbar puncture to check their neurofilaments and the OCBs after diagnosis?"

      Yes, you can, but they may not agree to it. There are only two labs in the UK that offer neurofilament levels; the CSF lab at Queen Square (my old lab) and our lab at Barts-MS.

      OCBs are routine across the country.

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