Background and Purpose: Carotid and vertebral artery dissections are frequently complicated by cerebral embolism. Detection of clinically silent circulating microemboli by transcranial Doppler sonography (TCD) is now widely investigated in patients with carotid artery disease in the hope to identify patients at increased risk for stroke. Methods: In 20 patients with carotid (n = 17) or vertebral (n = 2) artery dissection, or both (n = 1), we performed a 1-hour microembolus detection downstream to the dissection in the middle or in the posterior cerebral artery, respectively. Results: Five patients with a carotid artery stenosis of ≧90% or with carotid artery occlusion showed microembolic signals at a rate of up to 15 events/h. In all these patients, the onset of the dissection was within the last 58 days. Patients with lower degrees of stenosis or onset of symptoms beyond 58 days did not show microembolic signals at all. Three patients who had presented with recurrent ischaemic events prior to TCD monitoring unexceptionally had microembolic signals. Conclusion: Microembolic signals occur in patients with high-grade stenosis or occlusion due to acute cervical artery dissection. Patients with microemboli seem to be at increased macroembolic risk, i.e. stroke recurrence, and may require close-meshed clinical follow-up and possibly stronger antithrombotic treatment.

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Background: Intracranial arterial stenosis is a rare cause of stroke in Caucasians. Detection of clinically silent circulating microemboli by transcranial Doppler sonography is now widely investigated in patients with carotid artery disease in the hope to identify patients at increased risk for stroke. Methods: In 33 patients with intracranial internal carotid (n = 12), middle cerebral (n = 18), posterior cerebral (n = 2), or basilar artery stenosis (n = 1), we performed a 1-hour microembolus detection downstream to the stenosis in the middle or in the posterior cerebral artery, respectively. The stenosis was assessed by transcranial Doppler and duplex ultrasound. 18 patients had been symptomatic in the dependent territory. Results: Five patients with ischaemic symptoms within the last 8 days and with a peak systolic flow velocity of ≧210 cm/s in the stenosis showed microembolic signals at a rate of 3–25 events/h, despite effective anticoagulation. All these 5 patients had a lesion pattern on cranial CT or MRI scan suggesting embolic origin. All the asymptomatic patients (n = 15) and all the patients with a peak systolic intrastenostic velocity of 160 to <210 cm/s (n = 13) did not show microembolic signals at all. Conclusion: Microembolic signals occur in recently symptomatic patients with high-grade intracranial arterial stenosis indicated by a sonographically measured stenotic peak flow velocity of ≧210 cm/s. Therapeutic anticoagulation was not sufficient to suppress microemboli formation.

IntroductionSurfactant protein D (SP-D) is a collectin with immuno-regulatory functions, which may depend on oligomerization. Anti-microbial and anti-inflammatory properties have been attributed to multimeric SP-D variants, while trimeric subunits per se have been suggested to enhance inflammation. Previously, we reported low circulating SP-D in early rheumatoid arthritis (RA), and the present investigation aims to extend these data by serial SP-D serum measurements, studies on synovial fluid, SP-D size distribution and genotyping in patients with early RA.MethodsOne-hundred-and-sixty disease-modifying antirheumatic drug (DMARD) naïve RA patients with disease duration less than six months were studied prospectively for four years (CIMESTRA (Ciclosporine, Methotrexate, Steroid in RA) trial) including disease activity measures (C-reactive protein, joint counts and Health Assessment Questionnaire (HAQ) score), autoantibodies, x-ray findings and SP-D. SP-D was quantified by enzyme-linked immunosorbent assay (ELISA) and molecular size distribution was assessed by gel filtration chromatography. Further, SP-D Met11Thr single nucleotide polymorphism (SNP) analysis was performed.ResultsSerum SP-D was significantly lower in RA patients at baseline compared with healthy controls (P < 0.001). SP-D increased slightly during follow-up (P < 0.001), but was still subnormal at four years after adjustment for confounders (P < 0.001). SP-D in synovial fluid was up to 2.5-fold lower than in serum. While multimeric variants were detected in serum, SP-D in synovial fluid comprised trimeric subunits only. There were no significant associations between genotype distribution and SP-D. Baseline SP-D was inversely associated to CRP and HAQ score. A similar relationship was observed regarding temporal changes in SP-D and CRP (zero to four years). SP-D was not associated to x-ray findings.ConclusionsThis study confirms that circulating SP-D is persistently subnormal in early and untreated RA despite a favourable therapeutic response obtained during four years of follow-up. SP-D correlated negatively to disease activity measures, but was not correlated with x-ray progression or SP-D genotype. These observations suggest that SP-D is implicated in RA pathogenesis at the protein level. The exclusive presence of trimeric SP-D in affected joints may contribute to the maintenance of joint inflammation.Trial registration(j.nr NCT00209859).

Galectin-3 has been suggested as a pro-inflammatory mediator in animal arthritis and rheumatoid arthritis (RA). We aimed to study the serum level of galectin-3 in patients with newly diagnosed RA and associations with disease profile, Magnetic resonance imaging (MRI) findings and seromarkers of synovial matrix inflammation. One hundred and sixty DMARD naïve patients newly diagnosed with RA were included (CIMESTRA study). Clinical, serological and imaging data were recorded before treatment and at 6 weeks, 3 and 12 months. Galectin-3 and hyaluronan (HYA) were measured by ELISA (R&D and Corgenix, USA), and the N-terminal propeptide of type III collagen (PIIINP) by radioimmunoassay (Orion Diagnostica, Finland). One hundred and nineteen, 87 and 60 blood donors served as controls for galectin-3, HYA and PIIINP, respectively. Baseline galectin-3 was significantly elevated in anti-CCP positive (4.2 μg/l IQR [3.6;6.1]) patients as compared with anti-CCP negatives (4.0 μg/l [2.6;4.9], P = 0.05) and controls (3.8 μg/l [3.0;4.8], P < 0.01). During treatment, galectin-3 remained elevated, but increased transiently with peak values at 6 weeks. Galectin-3 correlated with baseline smoking, anti-CCP, and with MRI erosion score after 1 year of follow-up. HYA and PIIINP were elevated (P < 0.001) irrespective of anti-CCP status and correlated positively with synovitis assessed clinically and by MRI. HYA and PIIINP did not correlate with galectin-3. These observations indicate that HYA and PIIINP mainly reflect expansive synovitis proliferation while galectin-3 is more closely linked to autoimmunity, smoking and joint destructive processes.