Research: Grey Matter lesions in SPMS

Epub: Aviv et al. Decreased Frontal Lobe Gray Matter Perfusion in Cognitively Impaired Patients with Secondary-Progressive Multiple Sclerosis Detected by the Bookend Technique.AJNR Am J Neuroradiol. 2012 Apr 26.

BACKGROUND AND PURPOSE: There is increasing evidence implicating microvascular (small blood vessel) impairment in MS. Perfusion imaging (a marker of blood flow) offers a unique opportunity to investigate the functional impact of gray matter (GM) pathology. The investigators sought to quantify differences in MR imaging-based cerebral perfusion (blood flow) between cognitively impaired and nonimpaired SPMSers.

MATERIALS AND METHODS: MSers were prospectively recruited and assessed using MR imaging and the standard cognitive battery called the Minimal Assessment of Cognitive Function in MS. MSers exhibiting impairment on ≥2 individual tests were classified as cognitively impaired. Healthy controls were prospectively recruited and assessed using MR imaging to validate assumptions. Structural and perfusion scans were coregistered (overlayed on top of each other) and partitioned into anatomic brain regions and tissue compartments. Clinical and radiologic characteristics were compared between MSers with and without impairment to identify potential confounders.

RESULTS: Thirty-seven MSers with SPMS (age 56 ± 9 years; 23 women, 14 men) and 10 age- and sex-matched healthy controls were recruited. Assumptions were found to be valid in MS. GM and WM cerebral blood flow were all globally reduced in impaired MSers. After adjusting for potential confounders while examining sublobar level perfusion, only GM 
cerebral blood flow was significantly different between cognitive groups, and this hypoperfusion (reduced blood flow) localized to the bilateral medial superior frontal regions and left inferior, middle, and superior frontal regions (P < .005) of impaired MSers compared with nonimpaired patients.

CONCLUSIONS: Bookend-derived GM cerebral blood flow was significantly reduced in cognitively impaired patients with SPMS in functionally relevant brain regions.

“Chicken or egg? MS is a disease with extensive gray matter involvement; it causes damage and loss of gray matter. Gray matter is metabolically active, i.e. requires glucose and oxygen to function, these are delivered by the blood. If you have lost gray matter you get reduced blood flow, i.e. the remaining tissue needs less blood. So this study is simply stating the obvious. There is no evidence that reduced blood flow precedes the loss of gray matter in MS. This is another factor that needs to be taken into account by proponents of the vascular theory of MS; shrinkage of the brain or atrophy due to loss of brain tissue occurs throughout the course of MS and is linked to reduced blood flow. Therefore detecting reduced flow in say the veins draining the brain does not imply that it is causing MS, it is simply a consequence of the loss of brain tissue.” 

5 thoughts on “Research: Grey Matter lesions in SPMS”

  1. What are the real differences between SPMS and PPMS? The two sound really alike to me.

  2. Secondary progressive MS occurs after a number of relapsing remitting episodes (more common). Primary progressive MS doesn't and progresses straight off the bat(less common more often seen in males). The progression seen is due to nerve cell loss in the brain and spinal cord and so you're right, they are alike but one reveals itself earlier than the other.

  3. Re: "What are the real differences between SPMS and PPMS? The two sound really alike to me."The main differences relate to the definition, i.e. SPMS has an initial relapsing phase and PPMS does not. Once SPMS has started it behaves in the same way as PPMS. You may interested to note that ~5-20% of PPMSers have superimposed relapses. This is called relapsing progressive MS.

  4. In the most recent issue of the NMSS Momentum magazine, Timothy Coetzsee has a column about the NMSS's commitment to fund more research on progressive MS. He defines four types of "progressive MS": PPMS, SPMS, the silent progression of tissue injury often detected by MRI even without worsening symptoms and then he says it can sometimes refer to an MSer with severe disabilities. He says that we need a better understanding of the underlying mechanisms of progression in order to develop treatments (duh!). He mentions that researchers have learned that the EDSS is not sensitive to changes over the short periods that are typical in clinical trials and they're working on better measures for more quickly and effectively figuring out if a therapy is working (although he didn't mention LPs). He also states that trials that combine people with different types of progression can be like "mixing apples and oranges" and potentially dilute the results. So they are looking at the biological basis for categories like SPMS and PPMS. I've always sort of wondered about that since the four big categories seem to be somewhat arbitrary and were created by consensus. I suppose I worry about this because I don't seem to fit in any box so neatly. I had one mild, short-lived (ten days or so) incident that seemingly resolved completely, but in retrospect is hard to explain as anything other than a relapse. Several years later I got really sick and after that I developed new, mild symptoms, which only partially went away. After that, it's less clear. If I've had any relapses, they're not easily identifiable and have occurred against a background of slow, relentless progression. I do get these periods of what I think of as steeper slopes of decline, though.There seem to be a variety of schools of thought on SPMS vs. PPMS ranging from they're two different diseases to PPMS is just SPMS with the relapsing-remitting phase truncated off so they're the same entity. I've also read that people with SPMS or PPMS who have inflammatory activity seem to do better on DMD trials of existing meds.What do you think about the differences between SPMS vs. PPMS? Are researchers close to figuring this out? Do you think that the underlying biology is different? Are there other differences that are more salient, like the amount of inflammatory activity? Is it really likely to be so binary or more like a spectrum?

  5. I think the mixing "apples and pears" is not that there is are overt differnces in the mechanism. Their are subtle differences such as in demographics i.e age of onset, sex, etc. When do a trial having the group of MSers in the trial as similar as possible reduces the noise in the system and so increases the chance of finding differences in drug action, making it more likely to get a clear positive or negative result."Ive read that people"Yes there is evidence from trials that gadolinium enhancing progressive MSers may respond to current DMT.

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