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• BACKGROUND: Measuring perfusion provides a potential indication of metabolic activity in brain tissue. Studies in multiple sclerosis (MS) have identified areas of decreased perfusion in grey matter (GM) and white matter (WM), but the pattern in clinical subgroups is unclear.
  
  OBJECTIVES: This study investigated perfusion changes in differing MS clinical subgroups on or off beta-interferon therapy using a non-invasive MRI technique (continuous arterial spin labelling) to investigate whether different clinical MS subtypes displayed perfusion changes and whether this could give a further insight into the pathological mechanisms involved.
  
  METHODS: Sixty patients (21 relapsing remitting, 14 secondary progressive, 12 primary progressive, 13 benign) and 34 healthy controls were compared. Statistical parametric mapping (SPM '99) was used to investigate regional variations in perfusion in both GM and WM. Global WM perfusion was derived by segmenting WM from images using T(1) relaxation times.
  
  RESULTS: Regions of lower perfusion in predominantly GM were observed in the primary and secondary progressive cohorts, particularly in the thalamus. Increased WM perfusion was seen in relapsing remitting and secondary progressive cohorts.
  
  CONCLUSIONS: Low GM perfusion could reflect decreased metabolism secondary to neuronal and axonal loss or dysfunction with a predilection for progressive forms of MS. Increased WM perfusion may indicate increased metabolic activity possibly due to increased cellularity and inflammation. Improved methodology and longitudinal studies may enable further investigation of regional and temporal changes, and their relationship with physical and cognitive impairment. Full paper.

• The regional cerebral blood flow (rCBF) in 19 patients with multiple sclerosis (MS), 10 with a relapsing remitting course and 9 with a progressive course, was examined by single photon emission computed tomography (SPECT) using technetium-99m hexamethylpropyleneamine oxime ([99mTc]-d,l-HM-PAO) as flow tracer. Nine age-matched volunteers served as controls. Low rCBF in the frontal grey matter correlated with neurological disability (p < 0.01), low frontal grey and white matter perfusion correlated with impaired cognitive functions (p < 0.02), and low rCBF in the occipital regions correlated with impaired visual functions (p < 0.03) in the MS population. A relationship was also found between reduced parietal white matter perfusion and the duration of the disease (p < 0.005). Patients with progressive MS had significantly reduced rCBF in the frontal grey matter compared with relapsing remitting MS patients and controls (p < 0.05). No other rCBF differences were found.

Conclusions
The finding of significant differences between normal controls and MS patients in BOLD response patterns associated with a cognitive task in both task-positive and task-negative cortical networks sheds light on neuronal mechanisms of cognitive impairment in MS patients. Most remarkably, the inhibition of the default network appears to be impaired in posterior parietal and anterior medial prefrontal cortex and this impairment is reversed and in fact normalized by venoplasty. Since BOLD response is a function of cerebral blood flow and volume, and also oxygen metabolism rate, the reduced BOLD responses in both task positive and task-negative networks may reflect not only altered neuronal function but also change in cortical venous blood volume in MS. Thus the recovery of the suppression in the default network by angioplastic treatment may reflect recovered neuronal and/ or vascular function. Moreover the increase in the venous undershoot component of the BOLD response in MS as compared to controls and its reduction after venoplasty provides evidence of impaired clearance and CNS venous insufficiency and holds out the promise that this method may provide an objective diagnostic test.

ABSTRACT: BACKGROUND: Several studies have reported hypoperfusion of the brain parenchyma in multiple sclerosis (MS) patients. We hypothesized a possible relationship between abnormal perfusion in MS and hampered venous outflow at the extracranial level, a condition possibly associated with MS and known as chronic cerebrospinal venous insufficiency (CCSVI). METHODS: We investigated the relationship between CCSVI and cerebral perfusion in 16 CCSVI MS patients and 8 age- and sex-matched healthy controls. Subjects were scanned in a 3-T scanner using dynamic susceptibility, contrast-enhanced, perfusion-weighted imaging. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the gray matter (GM), white matter (WM) and the subcortical GM (SGM). The severity of CCSVI was assessed according to the venous hemodynamic insufficiency severity score (VHISS) on the basis of the number of venous segments exhibiting flow abnormalities. RESULTS: There was a significant association between increased VHISS and decreased CBF in the majority of examined regions of the brain parenchyma in MS patients. The most robust correlations were observed for GM and WM (r = -0.70 to -0.71, P < 0.002 and P corrected = 0.022), and for the putamen, thalamus, pulvinar nucleus of thalamus, globus pallidus and hippocampus (r = -0.59 to -0.71, P < 0.01 and P corrected < 0.05). No results for correlation between VHISS and CBV or MTT survived multiple comparison correction.
CONCLUSIONS: This pilot study is the first to report a significant relationship between the severity of CCSVI and hypoperfusion in the brain parenchyma. These preliminary findings should be confirmed in a larger cohort of MS patients to ensure that they generalize to the MS population as a whole. Reduced perfusion could contribute to the known mechanisms of virtual hypoxia in degenerated axons.

cheerleader wrote:It amazes me that we have ground breaking science being reported on this site--- (in some cases because posters from this site brought research to universities, and encouraged dialogue regarding CCSVI in MS) which is neglected in favor of squabbling and incessant name calling.