In multiple sclerosis (MS), MRI has emerged as the most useful paraclinical biomarker. ‘No evidence of disease activity’ is a desired outcome in therapeutic clinical trials and therapy monitoring in individual patients, which includes the absence of new or enhancing lesions on MRI. Therefore, frequent follow-up contrast-enhanced MRI examinations play an important role in disease monitoring.
In 2013, Kanda et al 1 described an increased signal intensity (SI) of the dentate nucleus (DN) on unenhanced T1-weighted MRI after multiple applications of gadolinium-based contrast agents (GBCAs) suggesting a deposition of gadolinium. Since then, numerous studies evaluated the effects of gadolinium deposition in the brain after serial application of GBCAs, and recent studies provide evidence that T1 hyperintensity of the DN is associated with the prior administrations of linear GBCAs, but not with macrocyclic GBCAs.2 3 However, the experience of an abnormal SI in the DN after more than 15 administrations of GBCAs is limited up to now.2 Since MS typically affects young adults, patients with MS commonly undergo a high number of MRI examinations through their lifetime. The aim of this study was to investigate the effect of 15 or more serial injections of the macrocyclic GBCA gadoterate meglumine on the SI of the DN on unenhanced T1-weighted images in patients with MS.
We retrospectively identified patients with relapsing-remitting MS who are at least 18 years of age and who underwent a minimum of 15 gadolinium-enhanced examinations in our institution that were all exclusively performed with the …
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Rapid advances in microbubble pharmacology together with novel ultrasound technologies for contrast-specific imaging of the macro- and microcirculation have led to a number of new applications for assessment of stroke patients. In particular, ultrasound perfusion imaging has added new perspectives for diagnosis and monitoring of both ischemic and hemorrhagic stroke. Recently, real-time brain perfusion imaging of middle cerebral artery infarctions has been introduced and new quantitative algorithms for evaluation of regional cerebral blood flow are being applied for the first time in humans. Microbubbles enable visualization of carotid artery plaque neovascularization to detect plaque vulnerability. There is growing interest in therapeutic applications of ultrasound, particularly in the field of sonothrombolysis. The treatment of acute ischemic stroke can be improved by ultrasound and microbubbles in combination with thrombolytic drugs. Excitingly, ultrasound and microbubbles may be effective in clot lysis of ischemic stroke even without additional thrombolytic drugs. New therapeutic avenues include opening of the blood-brain barrier (BBB) with ultrasound and microbubbles to enable novel drug delivery to the brain. Microbubbles are also assuming a central role in ultrasound molecular imaging with many targets of interest for evaluating pathophysiologic processes involved in cerebrovascular disease including angiogenesis, inflammation, and thrombus formation. Keywords: Microbubbles, ultrasound, stroke, therapy, sonothrombolysis, perfusion
Background and hypothesis Functional improvement after middle cerebral artery ischaemia seems to depend on recanalization of large-vessel occlusion as early as possible. The only approved medical treatment for acute stroke is early IV tissue plasminogen activator administration. However, while some patients do not benefit from quick recanalization, others recover despite persistent middle cerebral artery occlusion. We wondered whether there are different effects of tissue plasminogen activator treatment on large artery and small artery reopening. Methods We enrolled 55 acute stroke patients who showed persisting middle cerebral artery occlusion evidenced by transcranial colour-coded duplex ultrasonography in follow-up examination within 48 h postonset of middle cerebral artery stroke syndromes (mean 30·8 ± 5·4 h after admission). Twenty-two of 55 had been treated with tissue plasminogen activator and 33/55 had been treated without tissue plasminogen activator. We compared neurological (National Institutes of Health Stroke Scale) and functional (modified Rankin Scale) scores at baseline, after seven-days, and then after two-months. Risk factors, previous stroke prophylaxis, as well as clinical baseline characteristics were analysed to exclude significant differences between both groups. Results Despite later admission to hospital (tissue plasminogen activator patients 1·6 ± 0·66 h vs. non-tissue plasminogen activator patients 7·4 ± 5·84 h; P < 0·001), there was no significant difference between both groups concerning demographic data, severity of symptoms on admission, risk factors, stroke prophylaxis, as well as basic laboratory values (international normalized ratio, leucocyte count, C-reactive protein) blood pressure and body temperature on admission. Irrespective of Doppler findings demonstrating persistent middle cerebral artery occlusion in all 55 patients, there was a significant neurological and functional improvement in tissue plasminogen activator patients compared to non-tissue plasminogen activator patients. Tissue plasminogen activator patients had a mean improvement on National Institutes of Health Stroke Scale within the first seven-days of 2·8 points, while non-tissue plasminogen activator patients deteriorated by 2·2 points ( P < 0·001). Concerning modified Rankin Scale tissue plasminogen activator-treated patients showed a mean improvement within the first seven-days of 0·5 points, while non-tissue plasminogen activator patients deteriorated by 0·3 points ( P = 0·019). A favourable overall short-term clinical course (i.e. improvement on National Institutes of Health Stroke Scale >3 points and/or modified Rankin Scale >1 point) was found in 36·4% of tissue plasminogen activator patients and in 6·1% of non-tissue plasminogen activator patients ( P = 0·0047). At two-months follow-up, patients still showed a median modified Rankin Scale of 4 points after tissue plasminogen activator treatment and 5 points after non-tissue plasminogen activator treatment ( P = 0·023). Conclusion Although the prognosis of patients with persisting middle cerebral artery occlusion after tissue plasminogen activator administration is known to be poor, patients do better if treated with tissue plasminogen activator vs. those who could not be treated – mainly for late presentation. This may be due to sufficient small vascular territory recanalization despite persistence of large artery occlusion after tissue plasminogen activator treatment.
Background and Purpose- Relative signal intensity of acute ischemic stroke lesions in fluid-attenuated inversion recovery (fluid-attenuated inversion recovery relative signal intensity [FLAIR-rSI]) magnetic resonance imaging is associated with time elapsed since stroke onset with higher intensities signifying longer time intervals. In the randomized controlled WAKE-UP trial (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke Trial), intravenous alteplase was effective in patients with unknown onset stroke selected by visual assessment of diffusion weighted imaging fluid-attenuated inversion recovery mismatch, that is, in those with no marked fluid-attenuated inversion recovery hyperintensity in the region of the acute diffusion weighted imaging lesion. In this post hoc analysis, we investigated whether quantitatively measured FLAIR-rSI modifies treatment effect of intravenous alteplase. Methods- FLAIR-rSI of stroke lesions was measured relative to signal intensity in a mirrored region in the contralesional hemisphere. The relationship between FLAIR-rSI and treatment effect on functional outcome assessed by the modified Rankin Scale (mRS) after 90 days was analyzed by binary logistic regression using different end points, that is, favorable outcome defined as mRS score of 0 to 1, independent outcome defined as mRS score of 0 to 2, ordinal analysis of mRS scores (shift analysis). All models were adjusted for National Institutes of Health Stroke Scale at symptom onset and stroke lesion volume. Results- FLAIR-rSI was successfully quantified in stroke lesions in 433 patients (86% of 503 patients included in WAKE-UP). Mean FLAIR-rSI was 1.06 (SD, 0.09). Interaction of FLAIR-rSI and treatment effect was not significant for mRS score of 0 to 1 (P=0.169) and shift analysis (P=0.086) but reached significance for mRS score of 0 to 2 (P=0.004). We observed a smooth continuing trend of decreasing treatment effects in relation to clinical end points with increasing FLAIR-rSI. Conclusions- In patients in whom no marked parenchymal fluid-attenuated inversion recovery hyperintensity was detected by visual judgement in the WAKE-UP trial, higher FLAIR-rSI of diffusion weighted imaging lesions was associated with decreased treatment effects of intravenous thrombolysis. This parallels the known association of treatment effect and elapsing time of stroke onset.
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