Thursday, 1 January 2015

Childhood MS

Aubert-Broche et al. Onset of multiple sclerosis before adulthood leads to failure of age-expected brain growth . Published online before print, doi: 10.1212/WNL.0000000000001045 Neurology, 2014  83 2140-2146 

Objective: To determine the impact of paediatric-onset multiple sclerosis (MS) on age-expected brain growth. 


Methods: Whole brain and regional volumes of 36 patients with relapsing-remitting MS onset prior to 18 years of age were segmented in 185 longitudinal MRI scans (2–11 scans per participant, 3-month to 2-year scan intervals). MRI scans of 25 age- and sex-matched healthy normal controls (NC) were also acquired at baseline and 2 years later on the same scanner as the MS group. A total of 874 scans from 339 participants from the NIH-funded MRI study of normal brain development acquired at 2-year intervals were used as an age-expected healthy growth reference. All data were analyzed with an automatic image processing pipeline to estimate the volume of brain and brain substructures. Mixed-effect models were built using age, sex, and group as fixed effects. 


Results: Significant group and age interactions were found with the adjusted models fitting brain volumes and normalized thalamus volumes (p < 10−4). These findings indicate a failure of age-normative brain growth for the MS group, and an even greater failure of thalamic growth. In patients with MS, T2 lesion volume correlated with a greater reduction in age-expected thalamic volume. To exclude any scanner-related influence on our data, we confirmed no significant interaction of group in the adjusted models between the NC and NIH MRI Study of Normal Brain Development groups. 


Conclusions: Our results provide evidence that the onset of MS during childhood and adolescence limits age-expected primary brain growth and leads to subsequent brain atrophy, implicating an early onset of the neurodegenerative aspect of MS.


Brain and thalamic volumes in NIH Normal Brain Development (NIHPD) study and MS groups.

This is a sad piece of research to report for the new year, but I'm hoping that this will highlight to our patients, clinicians, health care providers and funding bodies that MS has tangible measurable disability. 


We need to stop talking about MS purely as an inflammatory disorder and start appreciating that it is a neurodegenerative disorder, no different from dementia or motor neurone disease. The only caveat being that we can change this by treating early. 

In their introductory paragraph, the authors point out that deep grey matter volume loss (the area of the brain where everything goes through - aka King's Cross St Pancreas of the brain) is measurable even in the first few years after the first attack.

In this work instead of simply looking across a group of healthy controls, MS boys and MS girls, which would have simply shown reduced brain volumes in the MS group relative to controls. The authors have looked ahead into the future and measured brain volumes over time at 2 or 3 time points, with approximately 24 months between scans. This allows you to measure brain growth, the exact opposite.

The results clearly show that childhood MS impairs age-expected brain growth (see above graphs). In the authors own words, "the marked impairment in age-expected growth and the subsequent brain atrophy indicates a clear failure of the anticipated resiliency of the maturing CNS to the brain injury mitigated by MS". For those who still believe that there is such a thing as benign MS, the graph below shows us that this by no means the case. The failure of thalamic growth is even more evident in those with higher lesion load than those with minimal lesion load. 




NIHPD group and MS groups with participants who have lesion-to-brain ratio inferior to 0.35% (minimal lesion load) and those with lesion-to-brain ratio superior to 0.35% (higher lesion load).

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