Early blood flow problems to cortex in MSers is associated with cognitive impairment. #MSBlog #MSResearch
“There has been an extensive debate on this blog about the possibility of there being a vascular hypothesis that underpins MS. This debate has largely been driven by the social phenomenon of CCSVI. Now that CCSVI has been discredited as a MS-specific entity we must not discard the possibility that blood flow, or perfusion, is not involved in the pathogenesis of MS.”
“In this study below, in early RRMS, the investigators show that prior to loss of grey matter that occurs in MS there is a perfusion deficit to this area of the brain. Perfusion means a lack of blood flow. What does this mean? It does not necessarily mean that the reduced blood flow is the problem. A more likely explanation is that the tissue requirements for blood are reduced. Various tissues of the body, grey matter included, have mechanisms to regulate their own blood supply. If you need more oxygen and energy the tissues lower their pH, which cause the arterioles (small arteries) to dilate, or get larger, which increases the blood flow to the tissues and vice versa. This process is very efficient and maximises the use of oxygen and energy (glucose and fats) both locally in organs and throughout the body. If you study biology this is part of what we call homeostasis.”
“This reduced grey matter perfusion is telling us that the cortex needs less blood, i.e. oxygen and/or energy, hence there must be a problem with its functioning. To me this indicates that the grey matter neurones are either dying, dead or sick and hence don’t need as much blood. This blood flow or perfusion deficit occurs before overt atrophy or shrinking of the grey matter is seen. This is what you would expect; tissue damage always precedes shrinkage or atrophy which is a delayed response. The timing of this delay between tissue damage and atrophy is important; is it 6, 12 or 24 months? We need to know this as we are beginning to use brain and focal grey matter atrophy as an outcome measure in clinical trials and possibly in clinical practice to monitor the effects of DMTs. It is not surprising that reduced blood flow is associated with reduced cognition; the grey matter is the stuff that makes us think and remember things.”
“This study indicates that there must be a more diffuse disease process occurring in the grey matter of MSers that precedes focal lesions and brain atrophy. The fact that it is occurring in the cortex an area of brain that abuts on the cerebrospinal fluid or CSF suggests it may have something to do with the CSF. Could there be a toxin or virus in the CSF? Could this toxin be the toxin from MS-related human endogenous retrovirus or HERV? Other contenders for this could be immunoglobulins or antibodies in the CSF or one of the many soluble inflammatory mediators. What this study also exposes so brutally is how little we know about the disease processes of early MS and how much we still have to learn.”
Epub: Debernard et al. Reduced grey matter perfusion without volume loss in early relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013 Sep 13.
BACKGROUND: Grey matter (GM) pathology in MS is associated with progressive long-term disability. Detection of GM abnormalities in early MS may therefore be valuable in understanding and predicting the long-term course. However, structural MRI measures such as volume loss have shown only modest abnormalities in early RRMS. This study therefore looked for evidence of abnormality in GM perfusion (blood flow), consistent with metabolic dysfunction, in early RRMS.
METHODS: 25 RRMSers with ≤5 years disease duration and 25 age-matched healthy controls underwent 3 Tesla MRI with a pseudo-continuous arterial spin labelling sequence to quantify GM perfusion and a volumetric T1-weighted sequence to measure GM volume. Neurological status was assessed in patients and neuropsychological evaluation undertaken in all subjects. Voxel-based analysis was used to compare regional GM perfusion and volume measures in MSers and controls.
RESULTS: There was reduced global GM perfusion in MSers versus controls (50.6±5.8 mL/100 g/min vs 54.4±7.6 mL/100 g/min, p=0.04). Voxel-based analysis revealed extensive regions of decreased cortical and deep GM perfusion in MSers. Reduced perfusion was associated with impaired memory scores. There was no reduction in global or regional analysis of GM volume in MSers versus controls.
CONCLUSIONS: The decrease in GM perfusion in the absence of volume loss is consistent with neuronal metabolic dysfunction in early RRMS. Future studies in larger cohorts and longitudinal follow-up are needed to investigate the functional and prognostic significance of the early GM perfusion deficits observed.