Dynamic Evolution of Diffusion-Weighted Imaging Lesions in Patients With Minor Ischemic Stroke

Kate, Mahesh; Riaz, Parnian; Gioia, Laura; Sivakumar, Leka; Jeerakathil, Thomas; Buck, Brian; Beaulieu, Christian; Butcher, Ken

doi:10.1161/strokeaha.115.009775

Cited by 11 publications

(6 citation statements)

References 6 publications

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“…32 Furthermore, the measured volumes on diffusion do not match with the final volume, especially in treated patients. 33,34 A potential association between neutrophil abnormalities and the progression of damage in the penumbra and the final ischemic volume have to be explored in further studies. In addition, we had a relatively limited number of patients, and our observations must be corroborated in larger cohorts.…”

Section: Discussionmentioning

confidence: 99%

Harmful neutrophil subsets in patients with ischemic stroke

Weisenburger‐Lile

Dong

Yger

et al. 2019

Neurol Neuroimmunol Neuroinflamm

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ObjectiveTo better understand the functional state of circulating neutrophils in patients with ischemic stroke (IS) for planning future clinical trials.MethodsWe analyzed by flow cytometry activation state of circulating neutrophils and the distribution of neutrophil peripheral subsets in 41 patients with acute IS less than 6 hours before admission and compared them with 22 age-matched healthy controls.ResultsOur results demonstrated continuous basal hyperactivation of circulating neutrophils during acute IS, characterized by lower l-selectin expression and higher CD11b expression at the cell surface, increased ROS production by neutrophils, and greater circulating levels of neutrophil elastase. Neutrophil hyperactivation was associated with deregulation of the equilibrium between apoptotic and necrotic. Patients also had higher percentages than controls of the overactive senescent (CXCR4bright/CD62Ldim) neutrophil subset and increased percentage of neutrophils with a reverse transendothelial migration (CD54highCXCR1low) phenotype. Importantly, neutrophil alterations were associated with the clinical severity of the stroke, evaluated by its NIH Stroke Scale score.ConclusionAltogether, our results indicate that during acute IS, the inflammatory properties of circulating neutrophils rise, associated with the expansion of harmful neutrophil subsets. These changes in neutrophil homeostasis, associated with disease severity, may play an instrumental role by contributing to systemic inflammation and to the blood-brain barrier breakdown. Our findings highlight new potential therapeutic approaches of stroke by rebalancing the ratio of senescent to immunosuppressive neutrophils or decreasing reverse neutrophil transmigration or both.

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Section: Discussionmentioning

confidence: 99%

Harmful neutrophil subsets in patients with ischemic stroke

Weisenburger‐Lile

Dong

Yger

et al. 2019

Neurol Neuroimmunol Neuroinflamm

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“…1–5,7 Figures for DWI lesions that resolved without visible lesion on follow-up likewise varied from 5.3% to 30%. 6–8 However, these studies assigned the entire lesion to a single category and thus did not account for within-lesion heterogeneity. We found that the part of an individual subcortical DWI lesion that cavitates or turns into a hyperintense lesion is often very small.…”

Section: Discussionmentioning

confidence: 99%

“…34,35 In accord with our results, studies on subcortical infarcts consistently showed that the final infarct size on long term follow-up is typically smaller than the initial DWI lesion. 3,7,8…”

Section: Discussionmentioning

confidence: 99%

Within-lesion heterogeneity of subcortical DWI lesion evolution, and stroke outcome: A voxel-based analysis

Duering

Adam

Wollenweber

et al. 2019

J Cereb Blood Flow Metab

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The fate of subcortical diffusion-weighted imaging (DWI) lesions in stroke patients is highly variable, ranging from complete tissue loss to no visible lesion on follow-up. Little is known about within-lesion heterogeneity and its relevance for stroke outcome. Patients with subcortical stroke and recruited through the prospective DEDEMAS study (NCT01334749) were examined at baseline ( n = 45), six months ( n = 45), and three years ( n = 28) post-stroke. We performed high-resolution structural MRI including DWI. Tissue fate was determined voxel-wise using fully automated tissue segmentation. Within-lesion heterogeneity at baseline was assessed by free water diffusion imaging measures. The majority of DWI lesions (66%) showed cavitation on six months follow-up but the proportion of tissue turning into a cavity was small (9 ± 13.5% of the DWI lesion). On average, 69 ± 25% of the initial lesion resolved without any visually apparent signal abnormality. The extent of cavitation at six months post-stroke was independently associated with clinical outcome, i.e. modified Rankin scale score at six months (OR = 4.71, p = 0.005). DWI lesion size and the free water-corrected tissue mean diffusivity at baseline independently predicted cavitation. In conclusion, the proportion of cavitating tissue is typically small, but relevant for clinical outcome. Within-lesion heterogeneity at baseline on advanced diffusion imaging is predictive of tissue fate.

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“…Finally, we also considered a possible effect of ELF-MF on the evolution of ischemic lesion size. The normal evolution of the infarct volume on MRI within first months after stroke is matter of debate 12 , 13 . In our sample, we observe infarct growth in 2 out of 3 patients treated for 45 minutes per day while in the group stimulated for 120 minutes, all the patients presented a reduction of the ischemic volume.…”

Section: Discussionmentioning

confidence: 99%

An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke

Capone

Liberti

Apollonio

et al. 2017

Sci Rep

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Extremely low frequency magnetic fields (ELF-MF) could be an alternative neuroprotective approach for ischemic stroke because preclinical studies have demonstrated their effects on the mechanisms underlying ischemic damage. The purpose of this open-label, one arm, dose-escalation, exploratory study is to evaluate the safety and tolerability of ELF-MF in patients with acute ischemic stroke. Within 48 hours from the stroke onset, patients started ELF-MF treatment, daily for 5 consecutive days. Clinical follow-up lasted 12 months. Brain MRI was performed before and 1 month after the treatment. The distribution of ELF-MF in the ischemic lesion was estimated by dosimetry. Six patients were stimulated, three for 45 min/day and three for 120 min/day. None of them reported adverse events. Clinical conditions improved in all the patients. Lesion size was reduced in one patient stimulated for 45 minutes and in all the patients stimulated for 120 minutes. Magnetic field intensity within the ischemic lesion was above 1 mT, the minimum value able to trigger a biological effect in preclinical studies. Our pilot study demonstrates that ELF-MF are safe and tolerable in acute stroke patients. A prospective, randomized, placebo-controlled, double-blind study will clarify whether ELF-MFs could represent a potential therapeutic approach.

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Dynamic Evolution of Diffusion-Weighted Imaging Lesions in Patients With Minor Ischemic Stroke

Abstract: The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl

Cited by 11 publications

References 6 publications

Harmful neutrophil subsets in patients with ischemic stroke

Harmful neutrophil subsets in patients with ischemic stroke

Within-lesion heterogeneity of subcortical DWI lesion evolution, and stroke outcome: A voxel-based analysis

An open-label, one-arm, dose-escalation study to evaluate safety and tolerability of extremely low frequency magnetic fields in acute ischemic stroke

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