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1: Eur J Neurol. 2008 Jul;15(7):725-9. Epub 2008 May 24. Links
Changing cerebral blood flow velocity detected by transcranial Doppler ultrasound during head up tilt in patients with multiple sclerosis.Gonul M, Asil T, Balci K, Celik Y, Turgut N, Uzunca I.
Erzurum Numune Hospital, Clinics of Neurology, Erzurum, Turkey.

BACKGROUND AND PURPOSE: Multiple sclerosis (MS) is a chronic inflammatory disease of central nervous system. We aimed to investigate the cerebral blood flow velocity (CBFV) changes in MS by transcranial Doppler. METHODS: Twenty patients with MS, 20 age-matched healthy controls were included in the study. In both groups, blood flow velocities (BFVs) of middle cerebral arteries (MCAs) were evaluated. The changes of blood pressure, heart rate along with the changes in BFV of MCA were recorded after the patients were raised to upright position. RESULTS: In both groups, upon raising the tilt table to the upright position, the mean CBFV values were found to be lower in comparison with the recorded baseline values (P values <0.05). The decline in the mean CBFV values was more significant in patients with MS (P = 0.01). CONCLUSION: Our study showed upon raise of the tilt table, the mean BFVs decreased more in MS patients than control group with a more prominent change in the subgroup of MS patients with expanded disability scale scores > or =2. By use of transcranial Doppler ultrasound, it may be possible to evaluate BFV changes in patients with MS.

PMID: 18505409 [PubMed - indexed for MEDLINE]

1: Med Hypotheses. 2008;70(6):1112-7. Epub 2008 Feb 20. Links
Raised venous pressure as a factor in multiple sclerosis.Talbert DG.
Institute of Reproductive and Developmental Biology, Imperial College School of Medicine, Du Cane Road, London W12 ONN, United Kingdom. d.talbert@imperial.ac.uk

It is hypothesised that the inflammatory condition seen in MS and the progressive myelopathy that is being successfully halted by obliteration of dural arteriovenous fistulas (DAVFs), may actually be two sides of the same coin. Excessive venous hypertension can stretch vein walls sufficiently to separate the tight junctions between endothelial cells forming the blood-brain-barrier (BBB). Colloids, etc., but not necessarily erythrocytes, could then pass through the exposed porous basement membranes. The resulting changes in osmotic pressure, etc. would disrupt the axon and dendrite internal transport systems, leading to their disintegration. The normal inflammatory processes which would follow, might be indistinguishable from those associated with autoimmune disease. Ascending progressive myelopathy and disablement are associated with an intracranial DAVF when its outflow enters the spinal venous system and descends past the cervical region. This can be arrested, and some degree of recovery produced, if the DAVF can be successfully eliminated or blocked. However, if the DAVF outflow is entirely into the spine, intracranial venous pressure may be normal and so there is nothing to alert the clinician to the presence of an intracranial DAVF. It is suggested that where spinal MS has been diagnosed from clinical observations, patients should be referred for angiological investigation to search for DAVFs within the head to identify any treatable subjects.

PMID: 18079069 [PubMed - indexed for MEDLINE]

1: Clin Neurophysiol. 2004 Jun;115(6):1473-8. Links
Cardiovascular autonomic dysfunction correlates with brain MRI lesion load in MS.Saari A, Tolonen U, Pääkkö E, Suominen K, Pyhtinen J, Sotaniemi K, Myllylä V.
Department of Neurology, Oulu University Hospital, P.O. Box 25, 90029 OYS, Oulu, Finland. anne.saari@ppshp.fi

OBJECTIVE: The aim of the present study was to investigate the cardiovascular autonomic control in clinically definite multiple sclerosis (MS) patients with a standardised battery of cardiovascular tests and to correlate these findings with the brain magnetic resonance imaging (MRI) lesion load. METHODS: Fifty-one patients with MS and 50 healthy controls were studied. Brain MRI was performed in all patients showing typical MS lesions. The cardiovascular tests were carried out using a standardised battery. RESULTS: Heart rate (HR) responses to deep breathing (P < 0.05) and tilt table testing (P < 0.001) were significantly decreased in MS patients when compared to those of the controls. Blood pressure (BP) responses in the tilt table test were also impaired in MS patients (diastolic P < 0.001, systolic P < 0.05). Of the different brain areas investigated the total volume of the midbrain MRI lesions (P < 0.05) was the one most clearly associated with the impaired BP responses. CONCLUSIONS: MS results in both reduced HR variation and decreased BP reactions indicating disturbed cardiovascular regulation. In particular, the midbrain lesions found in MS are associated with cardiovascular dysfunction.

PMID: 15134718 [PubMed - indexed for MEDLINE]

1: Med Hypotheses. 1986 Oct;21(2):141-8. Links
Damaging venous reflux into the skull or spine: relevance to multiple sclerosis.Schelling F.
Unequal propagation of central venous excess pressure into the different cerebral and spinal venous drainage systems is the rule rather than the exception. The intensity of the forces thus to be exerted on vulnerable cerebrospinal structures by the resulting pressure-gradients in the craniovertebral space is unknown. There is a need to consider the various conditions which may cause individual proneness to heavier reflux into particular cerebral as well as epi- and subdural spinal venous compartments. An attempt is made to indicate eventual consequences of excessive retrograde dilatation especially of internal cerebral veins. The importance of elucidating the neuropathological and clinical implications of undue reflux into the skull or spine is deduced from the probability of relations between localized backflow into the craniovertebral space and unexplicated cerebrospinal diseases. In this regard the features of multiple sclerosis are discussed.

PMID: 3641027 [PubMed - indexed for MEDLINE]

1: J Rheumatol. 2008 Mar;35(3):398-406. Epub 2008 Jan 15. Links
Endothelial dysfunction and atherosclerosis in rheumatoid arthritis: a multiparametric analysis using imaging techniques and laboratory markers of inflammation and autoimmunity.Kerekes G, Szekanecz Z, Dér H, Sándor Z, Lakos G, Muszbek L, Csipö I, Sipka S, Seres I, Paragh G, Kappelmayer J, Szomják E, Veres K, Szegedi G, Shoenfeld Y, Soltész P.
Cardiovascular Unit, Division of Rheumatology, and Laboratory of Immunology, Third Department of Medicine, Hungary.

OBJECTIVE: Cardiovascular disease is a leading cause of mortality in rheumatoid arthritis (RA). Endothelial dysfunction often precedes manifest atherosclerosis. We assessed endothelial dysfunction and atherosclerosis in RA in context with laboratory markers. METHODS: Fifty-two patients with RA and 40 matched healthy controls were studied. We assessed common carotid intima-media thickness (ccIMT) and flow- (FMD) and nitroglycerine-mediated vasodilation (NMD). We also assayed numerous immunological and metabolic laboratory markers. RESULTS: FMD was significantly lower in RA (5.32% +/- 4.66%) compared to controls (8.30% +/- 3.96%) (p = 0.001). NMD was preserved in RA. ccIMT was significantly greater in patients with RA (0.63 +/- 0.14 mm) versus controls (0.54 +/- 0.15 mm) (p = 0.012). In patients with RA, ccIMT correlated with FMD% (R = -0.318, p = 0.022), age (R = 0.831, p < 0.001), and anti-dsDNA levels (R = 0.463, p = 0.006). FMD% correlated with serum interferon-gamma (IFN-gamma) levels (R = 0.516, p = 0.014). NMD% correlated inversely with the percentage of Th0 lymphocytes (R = -0.636, p = 0.006), serum immune complex (R = -0.692, p < 0.001), and IgM levels (R = -0.606, p = 0.003). Patients with RA were divided as "low" (< 0.65 mm) versus "high" (> 0.65 mm) ccIMT groups, and into "normal" (> 5%) versus "impaired" (< 5%) FMD% subsets. Low and high ccIMT groups differed significantly in age and serum interleukin 1 (IL-1) and anti-dsDNA levels. RA patients with normal versus impaired FMD% differed significantly in age, disease duration, and serum IFN-gamma levels. Lipoprotein(a) [Lp(a)] also correlated with rheumatoid factor (RF) and C-reactive protein (CRP); homocysteine (HCy) correlated with CRP and correlated inversely with folate and vitamin B12 production. Paraoxonase-1 (PON-1) activity correlated with serum tumor necrosis factor-alpha(TNF-alpha) and IL-6 levels. CONCLUSION: This was a well characterized RA population, where FMD and ccIMT were impaired, indicating early endothelial dysfunction and accelerated atherosclerosis, respectively. RA-related autoimmune-inflammatory mechanisms and metabolic factors including anti-CCP, RF, CRP, circulating immune complexes, IgM, TNF-alpha, IL-6, Th0/Th1 ratio, HCy, folate, vitamin B12, and PON-1 may all be involved in the development of vascular disease in RA. Although ccIMT and FMD, as well as some laboratory factors, have been assessed by other investigators in RA-associated atherosclerosis, our results regarding the possible involvement of anti-CCP, anti-dsDNA, Lp(a), some cytokines, and PON-1 activity are novel. Early determination of FMD% and ccIMT may be useful to assess RA patients with high cardiovascular risk.

PMID: 18203326 [PubMed - indexed for MEDLINE]