In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.).

UK Medical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union, Netherlands Heart Foundation, and Mach-Gaensslen Foundation.

One of the characteristics of multiple sclerosis is the unpredictable occurrence of exacerbations and remissions. These fluctuations in disease activity are related to alterations in (auto-)immune activity. Exacerbations lead to short-term morbidity, but may also influence long-term disability. This longitudinal study in 73 patients with relapsing-remitting multiple sclerosis assessed the contribution of systemic infections to the natural course of exacerbations. In addition, we analysed whether infections lead to an increase in the number of gadolinium-enhancing lesions. A total of 167 infections and 145 exacerbations were observed during 6466 patient weeks. During a predefined at-risk period (ARP) of 2 weeks before until 5 weeks after the onset of a clinical infection (predominantly upper airway infections), there was an increased risk of exacerbations (rate ratio 2.1), which is in accordance with previous studies. Exacerbations with onset during the ARP led more frequently to sustained deficit [increase of > or =1 Expanded Disability Status Scale (EDSS) point or > or =0.5 above EDSS 5.5 for >3 months] than exacerbations with onset outside the ARP, with a rate ratio of 3.8. Minor and major exacerbations were equally distributed between the ARP and non-ARP onset groups. ARP exacerbations were associated with significantly higher plasma levels of the inflammatory marker soluble intracellular adhesion molecule 1 than non-ARP exacerbations, indicating relatively enhanced immune activation during ARP relapses. Three serial MRI scans were performed after the onset of an infection over a 6-week period. There was no difference in the number of gadolinium-enhancing lesions between the three time points. In conclusion, exacerbations in the context of a systemic infection lead to more sustained damage than other exacerbations. There is no indication that this effect occurs through enhanced opening of the blood-brain barrier.

Background and Purpose— Recent randomized trials have proven the benefit of intra-arterial treatment (IAT) with retrievable stents in acute ischemic stroke. Patients with poor or absent collaterals (preexistent anastomoses to maintain blood flow in case of a primary vessel occlusion) may gain less clinical benefit from IAT. In this post hoc analysis, we aimed to assess whether the effect of IAT was modified by collateral status on baseline computed tomographic angiography in the Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands (MR CLEAN). Methods— MR CLEAN was a multicenter, randomized trial of IAT versus no IAT. Primary outcome was the modified Rankin Scale at 90 days. The primary effect parameter was the adjusted common odds ratio for a shift in direction of a better outcome on the modified Rankin Scale. Collaterals were graded from 0 (absent) to 3 (good). We used multivariable ordinal logistic regression analysis with interaction terms to estimate treatment effect modification by collateral status. Results— We found a significant modification of treatment effect by collaterals ( P =0.038). The strongest benefit (adjusted common odds ratio 3.2 [95% confidence intervals 1.7–6.2]) was found in patients with good collaterals (grade 3). The adjusted common odds ratio was 1.6 [95% confidence intervals 1.0–2.7] for moderate collaterals (grade 2), 1.2 [95% confidence intervals 0.7–2.3] for poor collaterals (grade 1), and 1.0 [95% confidence intervals 0.1–8.7] for patients with absent collaterals (grade 0). Conclusions— In MR CLEAN, baseline computed tomographic angiography collateral status modified the treatment effect. The benefit of IAT was greatest in patients with good collaterals on baseline computed tomographic angiography. Treatment benefit appeared less and may be absent in patients with absent or poor collaterals. Clinical Trial Registration— URL: http://www.trialregister.nl and http://www.controlled-trials.com . Unique identifier: (NTR)1804 and ISRCTN10888758, respectively.

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