How long should we wait before trying to switch off the shredder? #ClinicSpeak #MSBlog #MSResearch
“MRI as a tool has matured and is now being used to look at the integrity of the brain and spinal cord. One method is diffusion tensor imaging, which is able to map the diffusion of water molecules in space. In the case of a white matter, or nerve fibre, tract this water diffusion should only be in one direction; the direction that the nerve fibres run in. Using DTI you can assess the anatomy of the fibre tracts and their structural integrity. If you have a disease that cuts, or shreds, fibre tracts such as MS you can assess the extent of damage using DTI.”
“This study below shows quite clearly that fibre tracts are damaged (shredded) very early in the course of MS and the damage gets worse with time. This is not a new observation. We know from numerous other studies that in most MSers, MS begins many years before the first clinical attack. Therefore to maximise brain health and brain integrity we really need to stop the shredding as soon as possible. This is why we continue to push the early effective treatment paradigm. Why wait for damage to get worse before treating this disease?”
“In the past the ABN guideline on treating MS stated that we should only treat CISers if they had 9 or more T2, or Gd-enhancing, lesions on their MRI. What is the difference between a CISer with only 2 T2 lesions on their baseline MRI study and a CISer with 17 T2 lesions on their baseline MRI scan? The latter CISer, with more lesions, is likely to have been unlucky and have had the disease longer and it is only now that his/her disease has declared itself. In comparison the person with 2 T2 lesions is lucky and in that their disease has declared itself much earlier and therefore has more to protect. This does not mean we shouldn’t treat the person with the high lesion load, it simply to make the point is why would we want to wait for the person with a low lesion load to acquire more damage (more lesions), and lose neuronal reserve, before we tried to suppress their MS disease activity? This study below supports this early treatment approach. Do you agree or disagree?”
Asaf et al. Injury to white matter tracts in relapsing-remitting multiple sclerosis: A possible therapeutic window within the first 5 years from onset using diffusion-tensor imaging tract-based spatial statistics. Neuroimage Clin. 2015 Apr 30;8:261-6.
Background: DTI (diffusion tensor imaging) studies in multiple sclerosis (MS) reveal white matter (WM) injury that occurs with disease progression.
Aims: In the present study we aimed to elucidate the relationship of microstructural WM damage in patients with varying periods of disease duration.
Methods: DTI scans were acquired from 90 MS patients and 25 healthy controls. Patients were grouped to short (<1 year), moderate (1 up to 6 years) and long (6-10 years) disease duration periods. Statistical analyses of the fractional anisotropy (FA) data were performed using tract-based spatial statistics (TBSS).
Results: Whole-brain skeletal FA measurements showed a significant decrease between healthy controls and the short MS disease duration group, as well as between moderate disease duration and long disease duration groups, but failed to show a significant difference between short and moderate disease duration groups. Voxelwise analysis revealed clusters of diffuse FA reductions in 40 WM tracts when comparing healthy controls and MS short disease duration group, with the point of maximal significant difference located in the left inferior longitudinal fasciculus. Comparing short with long disease duration groups, progressive FA reduction was demonstrated across 30 WM tracts, with the point of maximal significant difference migrating to the body of the corpus callosum.
Conclusions: A non-linear pattern of WM microstructure disruption occurs in RRMS. Alterations are seen early in the disease course within 1 year from onset, reach a plateau within the next 5 years, and only later additional WM changes are detected. An important period of a possible therapeutic window therefore exists within the early disease stage.