Venöse Multiple Sklerose Hypothese | CCSVI

These publications link blood perfusion problems and multiple sclerosis. Die Referenzen sind zeitlich geordnet, die neuesten zuerst.

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Durchblutung

1. [marrie10a] Marrie RA, Rudick R, Horwitz R, Cutter G, Tyry T, Campagnolo D, and Vollmer T: Vascular comorbidity is associated with more rapid disability progression in multiple sclerosis. Neurology. 2010 Mar;74(13):1041-7. PMID 20350978, doi:10.1212/WNL.0b013e3181d6b125, PDF, Article$. Interview.
   Health Sciences Center, GF-533, 820 Sherbrook Street, Winnipeg, MB R3A 1R9, Canada
   Abstract

   BACKGROUND: Vascular comorbidity adversely influences health outcomes in several chronic conditions. Vascular comorbidities are common in multiple sclerosis (MS), but their impact on disease severity is unknown. Vascular comorbidities may contribute to the poorly understood heterogeneity in MS disease severity. Treatment of vascular comorbidities may represent an avenue for treating MS. METHODS: A total of 8,983 patients with MS enrolled in the North American Research Committee on Multiple Sclerosis Registry participated in this cohort study. Time from symptom onset or diagnosis until ambulatory disability was compared for patients with or without vascular comorbidities to determine their impact on MS severity. Multivariable proportional hazards models were adjusted for sex, race, age at symptom onset, year of symptom onset, socioeconomic status, and region of residence. RESULTS: Participants reporting one or more vascular comorbidities at diagnosis had an increased risk of ambulatory disability, and risk increased with the number of vascular conditions reported (hazard ratio [HR]/condition for early gait disability 1.51; 95% confidence interval [CI] 1.41-1.61). Vascular comorbidity at any time during the disease course also increased the risk of ambulatory disability (adjusted HR for unilateral walking assistance 1.54; 95% CI 1.44-1.65). The median time between diagnosis and need for ambulatory assistance was 18.8 years in patients without and 12.8 years in patients with vascular comorbidities. CONCLUSIONS: Vascular comorbidity, whether present at symptom onset, diagnosis, or later in the disease course, is associated with a substantially increased risk of disability progression in multiple sclerosis. The impact of treating vascular comorbidities on disease progression deserves investigation.
   Comment Sclafani

   Dr. Sclafani: "....This paper did not really consider ccsvi at all. it spoke about vascular disease in the context of atherosclerotic disease and risk factors. Peripheral vascular disease was uncommon because they are focusing on arterial disease, something that would not be a commoon association with MS because of the ages of the patients.....in other words, this paper has nothing to do with ccsvi.
   Source: http://www.thisisms.com/ftopict-10981.html
   Comment Jelinek

   Zamboni's recent work on chronic cerebro-spinal venous insufficiency (CCSVI) has increased interest in vascular conditions in people with MS. Canadian researchers have now looked at 8,983 people with MS enrolled in the North American Research Committee on Multiple Sclerosis Registry, and analysed them according to whether they had vascular conditions such as heart disease, high blood pressure, diabetes, and so on. They found that having a vascular condition at the onset of MS resulted in around a 50% increased risk of having difficulty walking; for those who developed a vascular condition later, there was also roughly a 50% increased risk of difficulty walking. The risk increased the more vascular conditions a person had. Whereas it took about 19 years for a person with MS who did not have any vascular conditions to need assistance with walking, it took only 13 years for someone with a vascular condition.

   The researchers concluded that research was needed on the mechanisms by which vascular disease influences disability, whether treating the vascular conditions can reduce MS progression, and the role of lifestyle management in MS. What they didn't say was that there may well be a correlation with vascular conditions in other parts of the body and CCSVI, given that we know that people with vascular disease in one part of the body are likely to have or develop it in others. Download the full article above right.

   Source: Prof. G. Jelinek
2. [williams08a] Williams BJ, Skinner HJ, and Maria BL: Increased intracranial pressure in a case of pediatric multiple sclerosis. J Child Neurol. 2008 Jun;23(6):699-702. Type: Case Reports. PMID 18539995, doi:10.1177/0883073807313040.
   Department of Neurosciences, Charles P. Darby Children's Research Institute, Medical University of South Carolina, Charleston, SC, USA.
   Abstract

   A 15-year-old girl presented to our emergency department with dizziness, anorexia, nausea, and malaise. Clinical examination and magnetic resonance imaging studies showed characteristic features of multiple sclerosis. Surprisingly, a diagnostic lumbar puncture showed significant intracranial hypertension in addition to numerous oligoclonal bands, elevated immunoglobulin G index and immunoglobulin G/albumin ratio in the cerebrospinal fluid. It is proposed that a large burden of active demyelinating disease may cause increased intracranial pressure, thus providing an additional sound rationale for prompt therapeutic administration of intravenous high-dose steroids.
3. [inglese08a] Inglese M, Adhya S, Johnson G, Babb JS, Miles L, Jaggi H, Herbert J, and Grossman RI: Perfusion magnetic resonance imaging correlates of neuropsychological impairment in multiple sclerosis. J Cereb Blood Flow Metab. 2008 Jan;28(1):164-71. Epub 2007 May 02. PMID 17473851, doi:10.1038/sj.jcbfm.9600504.
   Department of Radiology, Hospital for Joint Disease, New York University School of Medicine, New York, New York 10016, USA.
   Abstract

   Although cognitive impairment is common in multiple sclerosis (MS), its pathophysiology is still poorly understood. Abnormalities of cerebral blood flow (CBF) have long been acknowledged in MS and advances in perfusion magnetic resonance imaging (MRI) allow for their assessment in vivo. We investigated the relationship between regional perfusion changes and neuropsychological (NP) dysfunctions in patients with relapsing-remitting and primary-progressive MS. Absolute CBF, cerebral blood volume (CBV) and mean transit time were measured in 32 MS patients and 11 healthy controls using dynamic susceptibility contrast-enhanced T2(*)-weighted MRI. A comprehensive NP test battery was administered to all patients. A mixed model analysis of covariance was performed for group comparisons in terms of perfusion measures in normal-appearing white matter (NAWM) and deep gray matter (GM). Pearson's correlations were used to describe the association of perfusion metrics with NP Z-scores. CBF and CBV values were significantly decreased in both NAWM and deep GM in MS patients compared with controls (P=0.01). In all patients, deep GM CBF was significantly associated with Rey Complex Figure Test (RCFT)-Copy (r=0.5; P=0.001) and deep GM CBV and NAWM CBV were significantly associated with Color-Word Interference Inhibition Switching test (D-KEFSIS) (r=0.4; P=0.008 and r=0.4; P=0.02). However, the only associations that remained significant after Bonferroni correction were between deep GM CBF and RCFT-Copy (P=0.006), and deep GM CBV and D-KEFSIS (P=0.04). Our results suggest a role for tissue perfusion impairment in NP dysfunction in MS. Large-scale studies are needed to characterize better this association.
4. [inglese07a] Inglese M, Park SJ, Johnson G, Babb JS, Miles L, Jaggi H, Herbert J, and Grossman RI: Deep gray matter perfusion in multiple sclerosis: dynamic susceptibility contrast perfusion magnetic resonance imaging at 3 T. Arch Neurol. 2007 Feb;64(2):196-202. PMID 17296835, doi:10.1001/archneur.64.2.196.
   Departments of Radiology and Neurology, Hospital for Joint Disease, New York University School of Medicine, 650 First Avenue, New York, NY 10016, USA.
   Abstract

   OBJECTIVES: To assess the presence of perfusion abnormalities in the deep gray matter of patients with relapsing-remitting and primary progressive multiple sclerosis (MS) in comparison with healthy controls and to investigate the impact of perfusion impairment on clinical disability and fatigue. DESIGN: Survey. SETTING: Research-oriented hospital. Patients Twenty-two patients with MS and 11 age- and sex-matched healthy volunteers. Intervention Absolute cerebral blood flow, cerebral blood volume, and mean transit time were measured in the thalamus, putamen, and caudate nuclei. MAIN OUTCOME MEASURES: Decrease of cerebral blood flow in the deep gray matter of patients with MS and correlation between perfusion impairment and the severity of fatigue. RESULTS: The cerebral blood flow value averaged over the thalamus, putamen, and caudate nuclei was significantly lower in patients with primary progressive MS (P<.001) and in patients with relapsing-remitting MS (P = .01) compared with controls, and there was a trend for patients with primary progressive MS to have lower average cerebral blood flow than patients with relapsing-remitting MS (P = .06). With respect to cerebral blood volume, there was a significant difference between patients with primary progressive MS and controls (P<.001) and between the 2 groups of patients (P = .03) but not between patients with relapsing-remitting MS and controls (P>.30). The fatigue score was significantly correlated with cerebral blood flow (r = 0.4; P<.001) and cerebral blood volume (r = 0.5; P = .004). CONCLUSION: The decrease of tissue perfusion in the deep gray matter of patients with MS is associated with the severity of fatigue.
5. [simon05a] Simon J: Ischemia and multiple sclerosis: perfusion MR imaging provides insight into an underexplored pathophysiology. AJNR Am J Neuroradiol. 2005 Jun-Jul ;26(6):1306-8. PMID 15956486.
6. [ge05a] Ge Y, Law M, Johnson G, Herbert J, Babb JS, Mannon LJ, and Grossman RI: Dynamic susceptibility contrast perfusion MR imaging of multiple sclerosis lesions: characterizing hemodynamic impairment and inflammatory activity. AJNR Am J Neuroradiol. 2005 Jun-Jul ;26(6):1539-47. PMID 15956527.
   Department of Radiology, New York University School of Medicine, NY 10016, USA.
   Abstract

   BACKGROUND AND PURPOSE: Perfusion measurement in multiple sclerosis (MS) may cast light on the disease pathogenesis and lesion development since vascular pathology is frequently demonstrated in the disease. This study was performed to investigate the perfusion characteristics in MS lesions using dynamic susceptibility contrast MR imaging (DSC-MRI) to better understand the hemodynamic changes in MS. METHODS: Seventeen patients with relapsing-remitting MS were studied with DSC-MRI. Perfusion measurements included cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT), were obtained in enhancing, non-enhancing lesions covered by DSC-MRI and contralateral normal appearing white matter (NAWM) in patients as well as normal white matter in seventeen control subjects. RESULTS: DSC-MRI data demonstrated reduced perfusion with significantly prolonged MTT (P < 0.001) in lesions and NAWM in patients compared with normal white matter in controls. Compared to contralateral NAWM, enhancing lesions demonstrate increased CBF (P = 0.007) and CBV (P < 0.0001), indicating inflammation-mediated vasodilatation. A K means cluster analysis was performed and identifies approximately 63.8% of non-enhancing lesions (Class 1) with significantly decreased perfusion (P < or = 0.0001) when compared with contralateral NAWM. In contrast, the remainder 36.2% non-enhancing lesions (Class 2) show increased CBV (P = 0.02) in a similar fashion to enhancing lesions and can be observed on quantitative color-coded maps even without blood-brain barrier breakdown. CONCLUSION: DSC-MRI measurements demonstrate potential for investigating hemodynamic abnormalities that are associated with inflammatory activity, lesion reactivity and vascular compromise in MS lesions. Non-enhancing lesions showed both low and high perfusion suggesting microvascular abnormalities with hemodynamic impairment and inflammatory reactivity that cannot be seen on conventional MRI.
7. [wuerfel04a] Wuerfel J, Bellmann-Strobl J, Brunecker P, Aktas O, McFarland H, Villringer A, and Zipp F: Changes in cerebral perfusion precede plaque formation in multiple sclerosis: a longitudinal perfusion MRI study. Brain. 2004 Jan;127(Pt 1):111-9. Epub 2003 21. PMID 14570816, doi:10.1093/brain/awh007.
   Institute of Neuroimmunology, Charité, Berlin, Germany.
   Abstract

   New MRI techniques such as the analysis of magnetization transfer or diffusion have provided evidence for subtle progressive alterations in tissue integrity prior to focal leakage of the blood-brain barrier (BBB) as part of plaque formation in multiple sclerosis. Since inflammation is capable of modulating the microcirculation, we investigated the hypothesis that changes in the local perfusion might be one of the earliest signs of lesion development. 20 patients with definite relapsing-remitting multiple sclerosis were analysed with regard to cerebral blood volume, cerebral blood flow, mean transit time and apparent diffusion coefficient (ADC), as well as conventional MRI parameters, on monthly follow-up scans. Among 89 gadolinium-enhancing lesions, we selected 18 that developed during the study and met strict inclusion criteria. In these, changes of perfusion parameters were detectable not only prior to the BBB breakdown, but also prior to increases in the ADC. Our data indicate that inflammation is accompanied by altered local perfusion, which can be detected prior to permeability of the BBB.
8. [newman94a] Newman NJ, Selzer KA, and Bell RA: Association of multiple sclerosis and intracranial hypertension. J Neuroophthalmol. 1994 Dec;14(4):189-92. Type: Case Reports. PMID 7881520.
   Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia.
   Abstract

   Three patients fulfilled the diagnostic criteria for both multiple sclerosis and pseudotumor cerebri. Although coincidence is possible, intracranial hypertension may be a manifestation of demyelinating disease.
9. [swank83a] Swank RL, Roth JG, and Woody DC: Cerebral blood flow and red cell delivery in normal subjects and in multiple sclerosis. Neurol Res. 1983 ;5(1):37-59. PMID 6140655.
   Abstract

   Regional cerebral blood flow (rCBF) was determined in 77 normal females and 53 normal males of different ages and in 26 men and 45 women with multiple sclerosis by the inhalation of radioactive Xe133 method. In the normal subjects the CBF was relatively high in the teens and fell, at first rapidly and then slowly in both sexes with age. During adult life the flow in females was significantly higher than in males. The delivery of packed red cells (RCD) was determined by multiplying the CBF by the percentage concentration of red cells (HCT). The RCD for both sexes was nearly the same. In the patients with multiple sclerosis there occurred a progressive generalized decrease in CBF and in RCD with age which was significantly greater than observed in normal subjects. The rate of decrease in CBF and RCD correlated directly with the rate of progress of the disease.

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