Wake-up Stroke Research Articles

What You Always Wanted to Know about Endovascular Therapy in Acute Ischemic Stroke but Never Dared to Ask: A Comprehensive Review.

In 2015, mechanical thrombectomy (MT) in combination with intravenous thrombolysis was demonstrated to be superior to best medical treatment alone in patients with anterior circulation stroke. This finding resulted in an unprecedented boost in endovascular stroke therapy, and MT became widely available. MT was initially approved for patients presenting with large vessel occlusion in the anterior circulation (intracranial internal carotid artery or proximal middle cerebral artery) within a 6-hour time window. Eventually, it was shown to be beneficial in a broader group of patients, including those without known symptom-onset, wake-up stroke, or patients with posterior circulation stroke. Technical developments and the implementation of novel thrombectomy devices further facilitated endovascular recanalization for acute ischemic stroke. However, some aspects remain controversial. Is MT suitable for medium or very distal vessel occlusions? Should emergency stenting be performed for symptomatic stenosis or recurrent occlusion? How should patients with large vessel occlusion without disabling symptoms be treated? Do certain patients benefit from MT without intravenous thrombolysis? In the era of personalized decision-making, some of these questions require an individualized approach based on comorbidities, imaging criteria, and the severity or duration of symptoms. Despite its successful development in the past decade, endovascular stroke therapy will remain a challenging and fascinating field in the years to come. This review aims to provide an overview of patient selection, and the indications for and execution of MT in patients with acute ischemic stroke.

Author Response: Stroke Among SARS-CoV-2 Vaccine Recipients in Mexico: A Nationwide Descriptive Study.

We appreciate the comment on our article.1 Dr. Stoiloudis reports the case of an otherwise healthy young male individual who developed a wake-up acute ischemic stroke after the second dose of BNT162b2. It is of interest that their patient developed a fever in close temporal association to vaccination, which may be explained by vaccination reactogenicity. Additional research on the potential pathophysiologic pathways for immunization-related strokes is needed. It would be interesting to clarify the stroke etiologic approach in this patient because the development of an acute stroke in close temporal association to the vaccine does not exclude other common stroke causes among young adults.2

Migraine aura-like symptoms at onset of stroke and stroke-like symptoms in migraine with aura.

Background and objectivesIn general, suddenly occurring neurological deficits, i.e., negative neurological symptoms, are considered symptoms of focal cerebral ischemia, while positive irritative symptoms with gradual onset are viewed as the characteristics of migraine aura. Nevertheless, cortical spreading depolarization, the pathophysiological basis of migraine aura, has also been observed in acute ischemic stroke. The aim of our study was to determine the frequency of migraine aura-like symptoms at ischemic stroke onset and stroke-like symptoms in migraine with aura.MethodsWe interviewed 350 consecutive patients with ischemic stroke and 343 with migraine with aura using a structured questionnaire. Stroke diagnosis was confirmed by imaging, and migraine with aura was diagnosed according to the current criteria of the International Headache Society. Patients with wake-up strokes or severe cognitive deficits that precluded a useful interview were excluded from the study.ResultsSeventy-eight patients with stroke (22.3%) reported visual symptoms, 145 (41.4%) sensory symptoms, 197 (56.3%) a paresis, and 201 patients (57.4%) more than one symptom, compared to 326 migraine patients with aura (95%) with visual symptoms (P < 0.001), 175 (51%) with sensory symptoms (p = 0.011), 50 (14.6%) with paresis (P < 0.001), and 211 (61.5%) with more than one symptom (p = 0.27). Among patients with stroke, migraine-like symptoms were frequent: 36 patients (46.2%) with visual disturbance and 78 (53.8%) with sensory symptoms experienced irritative sensations. Paresis-onset in stroke lasted longer than 5 min in 43 patients (21.8%). Spreading of sensory and motor symptoms occurred in 37 (25.5%) and 37 (18.8%) patients, respectively. Stroke-like negative symptoms in migraine with aura occurred in 39 patients (12%) with visual symptoms, in 55 (31.4%) with sensory symptoms, and paresis appeared suddenly in 14 patients (28%). More than one symptom in succession occurred in 117 patients with stroke (58.2%) and in 201 migraine with aura patients (95.3%; P < 0.001).ConclusionMany patients with stroke experience migraine-like symptoms at stroke onset, and many migraine with aura patients have stroke-like symptoms. Though overall the symptom frequencies of the two groups are significantly different, clarifying the differential diagnosis in an individual patient requires additional history elements, physical findings, or results of ancillary investigations.

An evaluation of the efficacy and safety of thrombolysis in patients with wake-up stroke using the combination of inflammatory factors Interleukin-6 and C-reactive protein with multi-mode magnetic resonance imaging

ObjectiveTo explore the efficacy and safety of using thrombolysis in patients with wake-up stroke (WUS). MethodsThe serum IL-6 and hs-CRP levels of the patients in both the experimental group and the standard group were measured before thrombolysis and at 1 and 24 h afterwards. National Institute of Health Stroke Scale (NIHHS) scores were also recorded at the same time points as well as at 10 and 90 d after thrombolysis, and modified Rankin Scale (mRS) scores were calculated before thrombolysis and at 10 and 90 d afterwards. The differences in all these observations before and after thrombolysis were then investigated. Results(1) The levels of serum IL-6 and hs-CRP in the experimental group and the standard group were higher than those in the healthy control group before thrombolysis (P < 0.05), indicating that higher levels of hs-CRP and IL-6 are risk factors for WUS (P < 0.05). (2) There were no significant differences in the serum hs-CRP and IL-6 levels of the patients in the experimental and standard groups before thrombolysis (P > 0.05). (3) The serum IL-6 and hs-CRP levels were positively correlated with the NIHHS scores in both the experimental group and the standard group (P < 0.05), and they correlated with the mRS scores at 90 d. ConclusionsInterleukin-6 and hs-CRP can be used as biological indicators of inflammatory injury and diagnosis of stroke, and the combined detection of IL-6 and hs-CRP is of importance in predicting a deterioration in stroke patients.

Ambient fine particulate pollution hysteresis triggers wake-up stroke and rapidly triggers non-wake-up stroke: a case-crossover study.

Atmospheric pollutants increase the risk of acute ischemic stroke (AIS) which has been widely reported. However, little is known about the relationships between air pollution and specific subsets of AIS, such as wake-up stroke (WUS) and non-wake-up stroke (non-WUS). This study aimed to explore the relationship between WUS and non-WUS and atmospheric pollutants. A total of 1432 patients (331 WUS patients and 1101 non-WUS patients) were admitted to a tertiary hospital from 2016 to 2019. A time-stratified case-crossover design and a conditional logistic regression model to study the associations of change in pollutant concentration with WUS and non-WUS events were constructed. Data analysis revealed that WUS-related risks increased 48 to 72h after the increase in the PM2.5 concentration (each 10μg/m3 increase, lag 0-72h) [threshold OR (95% CI):18μg/m3 1.03 (0.94-1.11), 35μg/m3 1.01 (0.92-1.12), 50μg/m3 1.04 (0.91-1.19)]; the non-WUS-related risk increased 1 to 6h after the increase in the PM2.5 concentration (each 10μg/m3 increase, lag 0-1h) [threshold OR (95% CI):18μg/m3 1.01 (0.98-1.03), 35μg/m3 1.00 (0.97-1.04), 50μg/m3 1.01 (0.96-1.05)] (lag 0-6h) [threshold OR (95% CI): 18μg/m3 1.00 (0.97-1.03), 35μg/m3 1.00 (0.97-1.04), 50μg/m3 1.01 (0.97-1.06)]; O3 exposure was related to WUS events, and its impact on WUS events was stronger and longer-lasting (1-96h) than its impact on non-WUS events (1-6h). Greater than or equal to 65years of age, overweight (BMI ≥ 25), and diabetes had a significantly greater risk of WUS associated with increased PM2.5 concentration in the previous 12-96h than patients without these conditions. Patients with hypertension and smoking had a significant risk of non-WUS associated with increased PM2.5 concentration in the previous 1-6h. The increase in PM2.5 concentration in the cold season increased the risk of both WUS and non-WUS events. Ambient air pollution hysteresis triggers WUS and rapidly triggers non-WUS, even if the degree of pollutant is relatively low. Patients with elderly, overweight, and diabetes appeared particularly susceptible to WUS, and patients with hypertension and smoking history were susceptible to non-WUS. We need to expand the sample for further investigation into mechanisms by which environmental pollutants trigger WUS or non-WUS.

Surrogate biomarkers of outcome for wake-up ischemic stroke

BackgroundWake-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.Methods4251 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.ResultsWake-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).ConclusionsInflammatory 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.

Endovascular treatment for wake-up stroke and daytime unwitnessed stroke: A meta-analysis

BackgroundEvidence from sources outside the typical clinical research setting, such as a real-world setting, may complement evidence from randomised controlled trials (RCTs). The aim of the present study was to carry out a meta-analysis of available real-world evidence that focused on the efficacy and safety of endovascular treatment in patients with wake-up stroke (WUS) or daytime unwitnessed stroke (DUS) compared to that in patients treated ≤ 6 h after the onset of an ischemic stroke. MethodsData mining was conducted on 1 May 2021 from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials Cochrane Library. The study reviewed all published that assessed the effect of endovascular treatment in WUS and DUS compared to that received by patients with ischemic stroke. Relevant data were extracted and the narrative was reviewed and analysed. The results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). FindingsThe meta-analysis showed no significant differences between the two groups in the rates of functional independence (OR, 0.81; 95% CI, 0.65–1.02; P = 0.07), symptomatic intracerebral haemorrhage (OR, 0.86; 95% CI, 0.57–1.30; P = 0.470), and all-cause mortality (OR, 0.92; 95% CI, 0.73–1.16; P = 0.50). There was also no heterogeneity between the trials. ConclusionThe pooled analysis provided evidence to support the use of endovascular treatment in WUS and DUS with favourable perfusion imaging. The meta-analysis confirmed the main findings of RCTs of endovascular treatment in WUS and DUS in a real-world setting and therefore strengthens the validity of this treatment strategy.

Wake-up Stroke Outcome Prediction by Interpretable Decision Tree Model.

Outcome prediction in wake-up ischemic stroke (WUS) is important for guiding treatment strategies, in order to improve recovery and minimize disability. We aimed at producing an interpretable model to predict a good outcome (NIHSS 7-day<5) in thrombolysis treated WUS patients by using Classification and Regression Tree (CART) method. The study encompassed 104 WUS patients and we used a dataset consisting of demographic, clinical and neuroimaging features. The model was produced by CART with Gini split criterion and evaluated by using 5-fold cross-validation. The produced decision tree model was based on NIHSS at admission, ischemic core volume and age features. The predictive accuracy of model was 86.5% and the AUC-ROC was 0.88. In conclusion, in this preliminary study we identified interpretable model based on clinical and neuroimaging features to predict clinical outcome in thrombolysis treated wake-up stroke patients.

Statistical analysis plan for the randomized controlled trial Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST)

BackgroundPatients with wake-up ischemic stroke are frequently excluded from thrombolytic treatment due to unknown symptom onset time and limited availability of advanced imaging modalities. The Tenecteplase in Wake-up Ischaemic Stroke Trial (TWIST) is a randomized controlled trial of intravenous tenecteplase 0.25 mg/kg and standard care versus standard care alone (no thrombolysis) in patients who wake up with acute ischemic stroke and can be treated within 4.5 h of wakening based on non-contrast CT findings.ObjectiveTo publish the detailed statistical analysis plan for TWIST prior to unblinding.MethodsThe TWIST statistical analysis plan is consistent with the Consolidating Standard of Reporting Trials (CONSORT) statement and provides clear and open reporting.DiscussionPublication of the statistical analysis plan serves to reduce potential trial reporting bias and clearly outlines the pre-specified analyses.Trial registrationClinicalTrials.govNCT03181360. EudraCT Number 2014-000096-80. WHO ICRTP registry number ISRCTN10601890.

Editors' Note: Cerebral Microbleeds and Treatment Effect of Intravenous Thrombolysis in Acute Stroke: An Analysis of the WAKE-UP Randomized Clinical Trial

Dr. Schlemm et al. performed a prespecified analysis of the association of cerebral microbleeds (CMBs) with the treatment effect of IV alteplase vs placebo in the randomized controlled WAKE-UP (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke) trial of patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch on MRI. Among 459 patients available for analysis, there was no evidence of reduced treatment effect of alteplase in the 98 (21.4%) patients who had at least 1 CMB on baseline imaging. However, CMBs were associated with a nonsignificant increased risk of symptomatic intracranial hemorrhage (ICH; 11.2% vs 4.2%; adjusted odds ratio 2.32, 95% CI 0.99–5.43). In response, Drs. Meinel and Seiffge highlight the importance of distinguishing patients with CMBs from cerebral amyloid angiopathy or other cerebral small vessel disease—who have an increased risk of postthrombolysis ICH—from those with other causes of CMBs and other such lesions on susceptibility-weighted imaging, like those seen after valve implantation, extracorporeal membrane oxygenation, or prolonged intensive care unit stay. They also recommend examining the interaction of CMBs and white matter hyperintensities to better elucidate the risk of postthrombolysis hemorrhage. Responding to these comments, the authors note that new CMBs in acute ischemic stroke patients after IV thrombolysis were associated with an increased risk of hemorrhagic complications in prior literature, whereas new CMBs after cardiac surgery were not associated with bleeding risk, suggesting different risk profiles for patients with different causes of acute CMBs—a topic meriting further investigation in histopathology and observational studies. This exchange highlights the challenges of disentangling cause-specific bleeding risks associated with CMBs when examining ICH outcomes in patients undergoing thrombolysis. Dr. Schlemm et al. performed a prespecified analysis of the association of cerebral microbleeds (CMBs) with the treatment effect of IV alteplase vs placebo in the randomized controlled WAKE-UP (Efficacy and Safety of MRI-Based Thrombolysis in Wake-Up Stroke) trial of patients with acute ischemic stroke with unknown time of symptom onset and diffusion-weighted imaging–fluid-attenuated inversion recovery mismatch on MRI. Among 459 patients available for analysis, there was no evidence of reduced treatment effect of alteplase in the 98 (21.4%) patients who had at least 1 CMB on baseline imaging. However, CMBs were associated with a nonsignificant increased risk of symptomatic intracranial hemorrhage (ICH; 11.2% vs 4.2%; adjusted odds ratio 2.32, 95% CI 0.99–5.43). In response, Drs. Meinel and Seiffge highlight the importance of distinguishing patients with CMBs from cerebral amyloid angiopathy or other cerebral small vessel disease—who have an increased risk of postthrombolysis ICH—from those with other causes of CMBs and other such lesions on susceptibility-weighted imaging, like those seen after valve implantation, extracorporeal membrane oxygenation, or prolonged intensive care unit stay. They also recommend examining the interaction of CMBs and white matter hyperintensities to better elucidate the risk of postthrombolysis hemorrhage. Responding to these comments, the authors note that new CMBs in acute ischemic stroke patients after IV thrombolysis were associated with an increased risk of hemorrhagic complications in prior literature, whereas new CMBs after cardiac surgery were not associated with bleeding risk, suggesting different risk profiles for patients with different causes of acute CMBs—a topic meriting further investigation in histopathology and observational studies. This exchange highlights the challenges of disentangling cause-specific bleeding risks associated with CMBs when examining ICH outcomes in patients undergoing thrombolysis.

Effect of admission time on provision of acute stroke treatment at stroke units and stroke centers-An analysis of the Swiss Stroke Registry.

Rapid treatment of acute ischemic stroke (AIS) depends on sufficient staffing which differs between Stroke Centers and Stroke Units in Switzerland. We studied the effect of admission time on performance measures of AIS treatment and related temporal trends over time. We compared treatment rates, door-to-image-time, door-to-needle-time, and door-to-groin-puncture-time in stroke patients admitted during office hours (Monday-Friday 8:00-17:59) and non-office hours at all certified Stroke Centers and Stroke Units in Switzerland, as well as secular trends thereof between 2014 and 2019, using data from the Swiss Stroke Registry. Secondary outcomes were modified Rankin Scale and mortality at 3 months. Data were eligible for analysis in 31,788 (90.2%) of 35,261 patients. Treatment rates for IVT/EVT were higher during non-office hours compared with office hours in Stroke Centers (40.8 vs 36.5%) and Stroke Units (21.8 vs 18.5%). Door-to-image-time and door-to-needle-time increased significantly during non-office hours. Median (IQR) door-to-groin-puncture-time at Stroke Centers was longer during non-office hours compared to office hours (84 (59-116) vs 95 (66-130) minutes). Admission during non-office hours was independently associated with worse functional outcome (1.11 [95%CI: 1.04-1.18]) and increased mortality (1.13 [95%CI: 1.01-1.27]). From 2014 to 2019, median door-to-groin-puncture-time improved and the treatment rate for wake-up strokes increased. Despite differences in staffing, patient admission during non-office hours delayed IVT to a similar, modest degree at Stroke Centers and Stroke Units. A larger delay of EVT was observed during non-office hours, but Stroke Centers sped up delivery of EVT over time. Patients admitted during non-office hours had worse functional outcomes, which was not explained by treatment delays.

Pre-Hospital and In-Hospital Delay in Acute Ischemic Stroke Patients in Indonesia: A Multi-center Study

Introduction: Little is known regarding pre-hospital and in-hospital delays in acute ischemic stroke (AIS) patients in Indonesia. This study aimed to evaluate the nature of these delays and identify factors causing pre-hospital delays among AIS patients in Indonesia. Methods: This was a prospective, observational study conducted among adult AIS patients in 3 hospitals in Surabaya during March–August 2019. Baseline characteristics along with time intervals both pre- and post-arrival of patients to the study sites were collected and analysed. Multiple logistic regression analyses with a stepwise forward model were performed to evaluate the factors contributing to the pre-hospital delay. Results: A total of 126 patients were recruited in this study. Mean age ± S.D. was 58.56 ± 10.71 years old. The mean ± S.D. time of pre-hospital delay and mean ± S.D. time to computerized tomography scan were 1,004±1,116.09 and 189±166.44 minutes, respectively. Only 18 out of 126 patients (14.29%) presented to the hospitals within 4.5-hour of intravenous thrombolysis (IVT) time window. However, only 3 patients (2.38%) ultimately received IVT. Wake-up stroke (OR=17.865; p=0.019), unawareness of the gravity of symptoms (OR=11.025; p=0.007), unawareness of stroke symptoms (OR=7.880; p=0.003) and referral patient (OR=7.819; p=0.008) were significantly associated with pre-hospital delay. Conclusion: Pre-hospital delay of AIS was very common and represented a challenging problem to improve stroke care in Indonesia. Wake-up stroke along with lack of patient understanding in recognizing stroke symptoms and ineffective referral system were the most prominent risk factors for pre-hospital delay in Indonesian AIS patients.

A prospective study of wake-up stroke patients presenting to the emergency department: a single-center cohort study.

This study aims to prospectively examine patients with ischemic wake-up stroke (WUS) presenting to the emergency department, to investigate the risk factors affecting the mortality occurring within 28, 90, and 180days, and to create a new scoring system for the prediction of 28-day mortality. Patients who presented to the emergency department with WUS findings between 01.07.2019 and 30.06.2020 were prospectively analyzed. Logistic regression analysis was performed to determine the factors affecting mortality and the modified Rankin scale (mRS). A total of 161 patients were included. Of the patients, 22.4% died within 28days and 40.4% within 180days. The presence of coronary artery disease (CAD) increased the 28-day mortality risk (p = 0.009) 3.57 times, 90-day mortality risk 2.15 times (p = 0.033), and 180-day mortality risk 2.18 times (p = 0.045). In order to be used in the prediction of 28-day mortality in patients with WUS, we developed the ischemic WUS mortality score (IWUSMOS), which consists of the middle cerebral artery (45 points), internal carotid artery (60 points), basilar artery (39 points), superior cerebellar artery (66 points) occlusion, hypertension (33 points), CAD (28 points), malignancy (100 points), and arrhythmia (23 points). With this scoring system, the 28-day mortality risk was determined as 0.05% when the total score was "43" whereas the mortality risk was found to be 95.0% when the total score was "187." We propose that IWUSMOS, a new scoring system, can be used to predict the 28-day mortality risk of patients with WUS.

Wake-up stroke and unknown-onset stroke; occurrence and characteristics from the nationwide Norwegian Stroke Register.

Population-based knowledge of the characteristics of wake-up stroke and unknown-onset stroke is limited. We compared occurrence and characteristics of ischaemic and haemorrhagic wake-up stroke, unknown-onset stroke and known-onset stroke in a nationwide register-based study. We included patients registered in the Norwegian Stroke Register from 2012 through 2019. Age, sex, risk factors, clinical characteristics, acute stroke treatment and discharge destination were compared according to stroke type and time of onset. Of the 60,320 patients included, 11,451 (19%) had wake-up stroke, 11,098 (18.4%) had unknown time of onset and 37,771 (62.6%) had known symptom onset. The proportion of haemorrhagic stroke was lower among wake-up stroke patients (1107/11,451, 9.7%, 95% CI: 9.1-10.2) than for known-onset stroke (5230/37,771, 13.8%, 95% CI: 13.5-14.2) and for unknown-onset stroke (1850/11,098, 16.7%, 95% CI: 16.0-17.4). Mild stroke (NIHSS <5) was more frequent in ischaemic wake-up stroke (5364/8308, 64.6%, 95% CI: 63.5-65.5) than in known-onset (16,417/26,746, 61.4%, 95% CI: 60.8-62.0) and unknown-onset stroke (3242/5853, 55.4%, 95% CI: 54.1-56.7), while baseline characteristics were otherwise similar to known-onset stroke. Unknown-onset stroke patients were more often female, lived alone and had more severe strokes compared to wake-up stroke and known-onset stroke patients. Unknown-onset stroke patients were more often in need of community-based health care on discharge and had a higher in-hospital mortality. Ischaemic wake-up strokes shared baseline characteristics with known-onset strokes, but tended to be milder. Ischaemic unknown-onset stroke patients differed significantly from wake-up stroke, emphasising the importance of considering them as separate entities.

Utilization of Emergent Magnetic Resonance Imaging in the Diagnosis of Acute Ischemic Stroke

Utilizing an emergent magnetic resonance imaging (MRI) pathway for emergency department patients with acute onset of stroke-like symptoms allows for optimization of acute ischemic stroke treatment. Emergent MRI increases the percentage of patients administered intravenous tissue plasminogen activator (IV tPA) and minimizes stroke-related long-term disabilities. MRI also reduces the overall cost of stroke-related care by (1) preventing unnecessary IV tPA administration and its associated hospital costs and (2) facilitating faster stroke etiology work-up and treatment plan initiation to reduce hospital length of stay. The primary purpose of this article is to summarize two hospitals’ experience utilizing an evidence-based emergent MRI pathway for patients presenting to the emergency department with stroke-like symptoms who may be IV tPA eligible. Secondary purposes are to describe (1) emergent MRI pathway challenges with implemented mitigation strategies and (2) case examples (wake-up stroke; mild stroke-like symptoms with acute ischemic stroke confirmed by MRI).

Successful thrombolysis of a wake-up stroke aided by Computed Tomography Perfusion (CTP) imaging: A case report

The AMJ is a peer-reviewed, triannual health journal published by Anuradhapura Clinical Society (ACS).The Journal strives to be a forum for all health professionals to publish original research and review articles in their area of expertise. The AMJ publishes articles in clinical medicine, public health and health promotion. Our priority is given to manuscripts on health related issues which affects the communities living in rural tropical communities. Established as a journal in 2006 as a publication parallel to ACS annual scientific sessions, the journal was relaunched as a proper journal in 2013. Anuradhapura Medical Journal is a member of COPE and is included on DOAJ.

Pathogenetic links between ischemic stroke and sleep-disordered breathing

The paper reviews the pathophysiological links between ischemic stroke and sleep-disordered breathing. We discuss well-known mechanisms, such as intermittent hypoxemia, disturbed sleep structure and fluctuations in intrathoracic pressure, autonomic imbalance, oxidative stress, as well as genetic factors and the role of glymphatic system. The impact of sleep-disordered breathing on the development of various subtypes of stroke (according to the TOAST classification) and the so-called “wake-up stroke” is presented.

Efficacy and safety of rt-PA intravenous thrombolysis in patients with wake-up stroke: A meta-analysis.

Background: Recombinant tissue plasminogen activator (rt-PA) is one of the most effective therapies for patients with acute ischemic stroke. However, wake-up stroke (WUS) is typically excluded from intravenous thrombolytic therapy because of the unclear time of symptom onset. Therefore, we aimed to assess the efficacy and safety of rt-PA intravenous thrombolysis in patients with WUS by meta-analysis.Methods: We completed a systematic literature search of PubMed, Embase, the Cochrane Library, and SinoMed and included relevant studies of WUS patients covering rt-PA thrombolysis and nonthrombolysis (published from January 1, 2000, to February 28, 2021, with no language restrictions). The primary outcomes included safety outcomes and functional outcomes. Safety outcomes were measured according to the incidence of symptomatic intracranial hemorrhage and mortality within 90 days. The efficacy outcomes were measured based on 90-day modified Rankin Scale scores. We assessed pooled data using either a random-effects model (when P < .10, I 2 > 50%) or a fixed-effects model (when P > .10, I 2 < 50%).Results: A total of 913 patients from 9 studies were included in the meta-analysis. All patients had ischemic stroke confirmed by computed tomography or magnetic resonance imaging. The incidence of modified Rankin Scale 0 to 2 was significantly higher in the rt-PA thrombolysis group compared with the nonthrombolysis group. And rt-PA thrombolytic WUS patients did not differ significantly from nonthrombolytic WUS patients in terms of 90-day mortality. However, the incidence of Symptomatic intracranial hemorrhage was also significantly higher in the rt-PA thrombolysis group than that in the nonthrombolysis group.Conclusions: Patients with WUS who received rt-PA thrombolysis had a significant positive effect within 90 days. In addition, although there was no significant increase in mortality, we need to be aware of the risk of intracranial hemorrhage transformation associated with rt-PA thrombolysis despite no obvious increase in mortality. The safety of rt-PA intravenous thrombolysis should be closely monitored in patients with WUS.

Supine blood pressure normalised by daytime series values is independently associated with ischaemic wake-up stroke

Purpose Wake-up stroke constitutes up to 1/4 of all ischaemic strokes; however, its pathomechanisms remain largely unknown. Although low nocturnal blood flow may be the underlying cause, little is known about blood pressure (BP) characteristic of wake-up stroke patients. The aim of our study was to look for differences in BP variables between wake-up stroke and known-onset stroke patients and to seek BP indices which could distinguish wake-up stroke patients from other stroke patients. Materials and Methods In the study, we included ischaemic stroke patients in whom office BP measurement and Ambulatory BP monitoring (ABPM) were recorded at day 7, after acute hypertensive response. The daytime period was defined as the interval from 6 a.m. to 10 p.m. From ABPM, we obtained parameters of BP variability. Additionally, we calculated the BP percentage differences defined as (supine office BP–average daytime BP)/average daytime BP for systolic, diastolic, and mean blood pressure. We calculated analogous indices for night-time. The univariate and multivariate relationships between BP variables and wake-up stroke were analysed. Results Among the recruited 120 patients (aged 61.6 ± 12.3; 88 [73%] males; the baseline National Institutes of Health stroke scale score 4 [3–8]), 36 (30%) had wake-up stroke. In a univariate analysis, the systolic and mean daytime and night-time BP differences were significantly lower in patients with wake-up stroke [(−1.92 (−11.55 to 3.95) vs 4.12 (−2.48 to 11.31), p = 0.006 and −6.20 (−12.32 to 7.42) vs 2.00 (−6.86 to 11.65), p = 0.029 for daytime, respectively; 0.00 (−9.79 to 11.82) vs 9.84 (0.00 to 18.25), p = 0.003 and 0.51 (−8.49 to 12.08) vs 7.82 (−2.47 to 20.39), p = 0.026, for night-time, respectively]. After adjustment for possible confounders, the systolic BP difference remained significantly associated with wake-up stroke (odds ratio = 0.96, 95% confidence interval = 0.92–1.00, p = 0.039). Conclusion The subacute office-ambulatory BP difference including the dynamic (systolic BP), but not static BP component was independently associated with wake-up stroke.

Diffusion-Weighted Imaging and Fluid-Attenuated Inversion Recovery Quantification to Predict Diffusion-Weighted Imaging-Fluid-Attenuated Inversion Recovery Mismatch Status in Ischemic Stroke With Unknown Onset.

Visual rating of diffusion-weighted imaging (DWI)-fluid-attenuated inversion recovery (FLAIR) mismatch can be challenging. We evaluated quantification of DWI and FLAIR to predict DWI-FLAIR mismatch status in ischemic stroke. In screened patients from the WAKE-UP trial (Efficacy and Safety of Magnetic Resonance Imaging-Based Thrombolysis in Wake-Up Stroke), we retrospectively studied relative DWI (rDWI SI) and FLAIR signal intensity (rFLAIR SI). We defined the optimal mean rFLAIR SI and interquartile range of the rDWI SI in the DWI lesion to predict DWI-FLAIR mismatch status. We investigated agreement between each quantitative parameter and the DWI-FLAIR mismatch and the association between both quantitative parameters. We evaluated the predictive value of the quantitative parameters for excellent functional outcome by logistic regression, adjusted for DWI lesion volume, treatment, age, and National Institutes of Health Stroke Scale score. In the rFLAIR and rDWI SI analysis, 213/369 and 241/421 subjects respectively had a DWI-FLAIR mismatch. A mean rFLAIR SI cutoff of 1.09 and interquartile range rDWI SI cutoff of 0.47 were optimal to predict the DWI-FLAIR mismatch with a sensitivity and specificity of 77% (95% CI, 71%-83%) and 67% (95% CI, 59%-74%), and 76% (95% CI, 70%-81%) and 72% (95% CI, 65%-79%), respectively. For both quantitative parameters, agreement with the DWI-FLAIR mismatch was fair (73%, κ=0.44 [95% CI, 0.35-0.54] for rFLAIR and 74%, κ=0.48 [95% CI, 0.39-0.56] for rDWI). Both quantitative parameters correlated moderately (Pearson R=0.54 [95% CI, 0.46-0.61]; P<0.001, n=367). The interquartile range rDWI SI (n=188), but not the mean rFLAIR SI (n=172), was an independent predictor of excellent functional outcome (odds ratio, 0.67 per 0.1 unit increase of interquartile range rDWI SI, 95% CI, 0.51-0.89, P=0.01). Agreement between the quantitative and qualitative approach may be insufficient to advocate DWI or FLAIR quantification as alternative for visual rating.