Wake-up stroke: imaging-based diagnosis and recanalization therapy

Zhang, Yulei; Zhang, Junfang; Wang, Xixi; Wang, Yan; Anderson, Craig S.; Wu, Yun-Cheng

doi:10.1007/s00415-020-10055-7

Cited by 13 publications

(8 citation statements)

References 118 publications

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“…No difference was found in DWI volume at admission and in clinical DWI mismatch in both group of patients. Findings that support the current trend that MRI or CT scan could be the best methods for extending the time window for wake-up IS patients [ 17 – 19 ].…”

Section: Discussionsupporting

confidence: 52%

“…In recent years, advanced neuroimaging techniques have led to the development of a variety of research works and clinical trials seeking to include many of these patients with undetermined stroke onset in reperfusion therapies. To replace the old onset time window concept, tissue time window was based on brain tissue post-ischemic changes under the guidance of neuroimaging, mainly through Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) [ 17 – 19 ]. In this sense, WAKE-UP trial demonstrated that intravenous thrombolysis with alteplase resulted in a better functional outcome than treatment with placebo among acute ischemic stroke patients with unknown onset-symptom time based on MRI guide (DWI-FLAIR mismatch) [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

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Surrogate biomarkers of outcome for wake-up ischemic stroke

Hervella

Alonso-Alonso²,

Pérez‐Mato

et al. 2022

BMC Neurol

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Background Wake-up ischemic stroke (IS) has been usually excluded from acute stroke therapy options for being outside of the safe treatment window. We identified risk factors, and clinical or molecular biomarkers that could be therapeutic targets for wake-up stroke prevention, thus hopefully leading to a decrease in its mortality and disability in medium to long-term outcome. Methods 4251 ischemic stroke (IS) patients from a prospectively registered database were recruited; 3838 (90.3%) had known onset-symptom time, and 413 (9.7%) were wake-up strokes. The main endpoint was to analyze the association between different serum biomarkers with wake-up IS episodes and their progression. Leukocytes count, serum levels of C-reactive protein, fibrinogen, interleukin 6 (IL-6), and vitamin D were analyzed as inflammation biomarkers; N-terminal pro-B-type Natriuretic-Peptide and microalbuminuria, used as atrial/endothelial dysfunction biomarkers; finally, glutamate levels as excitotoxicity biomarker. In addition, demographic, clinical and neuroimaging variables associated with the time-evolution of wake-up IS patients and functional outcome at 3 months were evaluated. Good and poor functional outcome were defined as mRS ≤2 and mRS > 2 at 3 months, respectively. Results Wake-up IS showed a poorer outcome at 3-months than in patients with known on-set-symptom time (59.1% vs. 48.1%; p < 0.0001). Patients with wake-up IS had higher levels of inflammation biomarkers; IL-6 levels at admission (51.5 ± 15.1 vs. 27.8 ± 18.6 pg/ml; p < 0.0001), and low vitamin D levels at 24 h (5.6 ± 5.8 vs. 19.2 ± 9.4 ng/ml; p < 0.0001) are worthy of attention. In a logistic regression model adjusted for vitamin D, OR was 15.1; CI 95%: 8.6–26.3, p < 0.0001. However, we found no difference in vitamin D levels between patients with or without clinical-DWI mismatch (no: 18.95 ± 9.66; yes: 17.84 ± 11.77 ng/mL, p = 0.394). No difference in DWI volume at admission was found (49.3 ± 96.9 ml in wake-up IS patients vs. 51.7 ± 98.2 ml in awake IS patients; p = 0.895). Conclusions Inflammatory biomarkers are the main factors that are strongly associated with wake-up IS episodes. Wake-up IS is associated with lower vitamin D levels. These data indicate that vitamin D deficiency could become a therapeutic target to reduce wake-up IS events.

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Section: Discussionsupporting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

Surrogate biomarkers of outcome for wake-up ischemic stroke

Hervella

Alonso-Alonso²,

Pérez‐Mato

et al. 2022

BMC Neurol

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“…Recent evidences have allowed an extension of the IVT time window for patients with unknown onset time and for those with a known onset time up to 9 h, thanks to the new “tissue-window” approach guided by advanced neuroimaging techniques [34, 35]. These include “wake-up strokes,” which is a non-negligible sub-group of AIS where patients had no abnormality before sleep while waking up with neurological deficits, accounting for up to 25% of all AISs [36]. 2021 ESO guidelines on IVT recommend IVT with alteplase for patients with AIS of 4.5–9 h duration (known onset time) and with CT or MRI core/perfusion mismatch, and for whom MT is either not indicated or not planned [20, 37].…”

Section: Acute Ischemic Stroke Treatmentmentioning

confidence: 99%

Treatments in Ischemic Stroke: Current and Future

Mosconi¹,

Paciaroni²

2022

Eur Neurol

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Background and Aim: Despite progress made over the last 30 years, stroke is still a leading cause of disability and mortality; likewise, its burden is expected to increase over the next decades, due to population growth and aging. The development of drugs with better safety-efficacy profiles as well as strategies able to improve ischemic stroke management from the pre-hospital setting is needed. Summary: The pathophysiology of ischemic stroke involves multiple pathways resulting in cerebral artery obstruction and brain tissue ischemia. To date, the only approved drug for acute ischemic stroke is intravenous thrombolytic alteplase. Intravenous thrombolysis (IVT) can be administered alone or in combination with endovascular treatment (EVT) with mechanical thrombectomy, in case of large vessel occlusion and generally within 6 h from symptoms onset. The risk of potential bleeding complications, especially symptomatic intracerebral hemorrhage, is one of the reasons for the reluctance to administer IVT. Tenecteplase is a promising alternative fibrinolytic agent, having a better safety profile than alteplase. Moreover, recent evidences have allowed an extension of the IVT ± EVT time window for patients with unknown onset time and for those with a known onset time thanks to the new “tissue-window” approach guided by advanced neuroimaging techniques, which also helps in collateral circulation estimation. Regarding primary-secondary prevention, researchers are focused on improving the efficacy of antithrombotic drugs with a “hemostasis-sparing” approach. Neuroprotective agents are also under development, particularly stem cells. The COVID-19 pandemic has critically stressed global healthcare systems, with collateral damage resulting in access delivery of only emergency care, such as ischemic stroke. Regarding telemedicine, it has had a minor role in acute stroke management, and with the onset of COVID-19, this role will most likely be adopted to increase access and delivery in stroke assessment, but also in the follow-up.

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“…The inclusion criteria for MT were as follows: (1) OTP within 6 h of stroke onset, (2) no evidence of intracranial hemorrhage (ICH), (3) M1 segment of the middle cerebral artery (M1), M2 segment of the middle cerebral artery (M2), internal cerebral artery (ICA), basilar artery (BA) on magnetic resonance (MR) angiography (MRA) or conventional angiography with clinical deficits. For patients with 6-24 h OTP, MT was indicated if there was an MR diffusion weighted imaging (DWI)-fluid-attenuated inversion recovery (FLAIR) mismatch [13,14], that is, an acute ischemic lesion on DWI without marked parenchymal hyperintensity on FLAIR, in patients with M1, M2, ICA, or BA occlusion on MRA and clinical deficits. Patients with a pre-morbid modified Rankin Scale (mRS) score 3-5 were excluded in the present study.…”

Section: Patientsmentioning

confidence: 99%

Current status of a helicopter transportation system on remote islands for patients undergoing mechanical thrombectomy

et al. 2021

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Background Mechanical thrombectomy (MT) is standard treatment for acute ischemic stroke (AIS) with large-vessel occlusion within 6 h of symptom onset to treatment initiation (OTP). Recent trials have extended the therapeutic time window for MT to within 24 h. However, MT treatment remains low in remote areas. Nagasaki Prefecture, Japan has many inhabited islands with no neurointerventionalists. Our hospital on the mainland is a regional hub for eight island hospitals. We evaluated clinical outcomes of MT for patients with AIS on these islands versus on the mainland. Methods During 2014–2019, we reviewed consecutive patients with AIS who received MT at our hospital. Patients comprised the Islands group and Mainland group. Patient characteristics and clinical outcomes were compared between groups. Results We included 91 patients (Islands group: 15 patients, Mainland group: 76 patients). Seven patients (46.7%) in the Islands group versus 43 (56.6%) in the Mainland group achieved favorable outcomes. Successful recanalization was obtained in 11 patients (73.3%) on the islands and 67 (88.2%) on the mainland. The median OTP time in the Islands was 365 min. In both the Islands and Mainland groups, the OTP time and successful recanalization were associated with functional outcome. The modified Rankin Scale (mRS) score at 90 days ≤2 was obtained in two patients and mRS = 3 in four patients among eight patients with OTP time >6 h. Conclusions Few patients with AIS on remote islands have received MT. Although patients who underwent MT on the islands had longer OTP, the clinical outcomes were acceptable. OTP time on remote islands must be shortened, as this is related to functional outcome. In some cases with successful recanalization, a favorable outcome can still be obtained even after 6 h. Even if OTP exceeds 6 h, it is desirable to appropriately select patients and actively perform MT.

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Wake-up stroke: imaging-based diagnosis and recanalization therapy

Cited by 13 publications

References 118 publications

Surrogate biomarkers of outcome for wake-up ischemic stroke

Surrogate biomarkers of outcome for wake-up ischemic stroke

Treatments in Ischemic Stroke: Current and Future

Current status of a helicopter transportation system on remote islands for patients undergoing mechanical thrombectomy

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