1.Therapeutic Trends of Cerebrovascular Disease during the COVID-19 Pandemic and Future Perspectives
James E. SIEGLER ; Mohamad ABDALKADER ; Patrik MICHEL ; Thanh N. NGUYEN
Journal of Stroke 2022;24(2):179-188
As of May 2022, there have been more than 400 million cases (including re-infections) of the systemic acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), and nearly 5 million deaths worldwide. Not only has the coronavirus disease 2019 (COVID-19) pandemic been responsible for diagnosis and treatment delays of a wide variety of conditions, and overwhelmed the allocation of healthcare resources, it has impacted the epidemiology and management of cerebrovascular disease. In this narrative review, we summarize the changing paradigms and latest data regarding the complex relationship between COVID-19 and cerebrovascular disease. Paradoxically, although SARS-CoV-2 has been associated with many thrombotic complications—including ischemic stroke—there have been global declines in ischemic stroke and other cerebrovascular diseases. These epidemiologic shifts may be attributed to patient avoidance of healthcare institutions due to fear of contracting the novel human coronavirus, and also related to declines in other transmissible infectious illnesses which may trigger ischemic stroke. Despite the association between SARS-CoV-2 and thrombotic events, there are inconsistent data regarding targeted antithrombotics to prevent venous and arterial events. In addition, we provide recommendations for the conduct of stroke research and clinical trial planning during the ongoing COVID-19 pandemic, and for future healthcare crises.
2.Neuroimaging of Acute Ischemic Stroke: Multimodal Imaging Approach for Acute Endovascular Therapy
Mohamad ABDALKADER ; James E. SIEGLER ; Jin Soo LEE ; Shadi YAGHI ; Zhongming QIU ; Xiaochuan HUO ; Zhongrong MIAO ; Bruce C.V. CAMPBELL ; Thanh N. NGUYEN
Journal of Stroke 2023;25(1):55-71
Advances in acute ischemic stroke (AIS) treatment have been contingent on innovations in neuroimaging. Neuroimaging plays a pivotal role in the diagnosis and prognosis of ischemic stroke and large vessel occlusion, enabling triage decisions in the emergent care of the stroke patient. Current imaging protocols for acute stroke are dependent on the available resources and clinicians’ preferences and experiences. In addition, differential application of neuroimaging in medical decision-making, and the rapidly growing evidence to support varying paradigms have outpaced guideline-based recommendations for selecting patients to receive intravenous or endovascular treatment. In this review, we aimed to discuss the various imaging modalities and approaches used in the diagnosis and treatment of AIS.
3.Outcome Prediction in Cerebral Venous Thrombosis: The IN-REvASC Score
Piers KLEIN ; Liqi SHU ; Thanh N. NGUYEN ; James E. SIEGLER ; Setareh Salehi OMRAN ; Alexis N. SIMPKINS ; Mirjam HELDNER ; Adam de HAVENON ; Hugo J. APARICIO ; Mohamad ABDALKADER ; Marios PSYCHOGIOS ; Maria Cristina VEDOVATI ; Maurizio PACIARONI ; Rascha von MARTIAL ; David S. LIEBESKIND ; Diana Aguiar de SOUSA ; Jonathan M. COUTINHO ; Shadi YAGHI ;
Journal of Stroke 2022;24(3):404-416
We identified risk factors, derived and validated a prognostic score for poor neurological outcome and death for use in cerebral venous thrombosis (CVT). Methods We performed an international multicenter retrospective study including consecutive patients with CVT from January 2015 to December 2020. Demographic, clinical, and radiographic characteristics were collected. Univariable and multivariable logistic regressions were conducted to determine risk factors for poor outcome, mRS 3-6. A prognostic score was derived and validated. Results A total of 1,025 patients were analyzed with median 375 days (interquartile range [IQR], 180 to 747) of follow-up. The median age was 44 (IQR, 32 to 58) and 62.7% were female. Multivariable analysis revealed the following factors were associated with poor outcome at 90- day follow-up: active cancer (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.62 to 27.14; P<0.001), age (OR, 1.02 per year; 95% CI, 1.00 to 1.04; P=0.039), Black race (OR, 2.17; 95% CI, 1.10 to 4.27; P=0.025), encephalopathy or coma on presentation (OR, 2.71; 95% CI, 1.39 to 5.30; P=0.004), decreased hemoglobin (OR, 1.16 per g/dL; 95% CI, 1.03 to 1.31; P=0.014), higher NIHSS on presentation (OR, 1.07 per point; 95% CI, 1.02 to 1.11; P=0.002), and substance use (OR, 2.34; 95% CI, 1.16 to 4.71; P=0.017). The derived IN-REvASC score outperformed ISCVT-RS for the prediction of poor outcome at 90-day follow-up (area under the curve [AUC], 0.84 [95% CI, 0.79 to 0.87] vs. AUC, 0.71 [95% CI, 0.66 to 0.76], χ2 P<0.001) and mortality (AUC, 0.84 [95% CI, 0.78 to 0.90] vs. AUC, 0.72 [95% CI, 0.66 to 0.79], χ2 P=0.03). Conclusions Seven factors were associated with poor neurological outcome following CVT. The INREvASC score increased prognostic accuracy compared to ISCVT-RS. Determining patients at highest risk of poor outcome in CVT could help in clinical decision making and identify patients for targeted therapy in future clinical trials.
4.Effect of culture conditions on pyocyanin production by recombinant pyocyanin-producing strain Pseudomonas aeruginosa PS39-phzM
Vinh Quang Nguyen ; Uyen Hoang Nguyen ; Thuan Chi Nguyen ; Anh T. N Dao ; Loi Thi Thanh Nguyen
Malaysian Journal of Microbiology 2023;19(no.3):282-290
Aims:
A suitable medium and cultivation parameters have an important role in the improvement of the production of pyocyanin pigment by Pseudomonas aeruginosa microorganism. The study aimed to optimize culture conditions and medium components for maximal pyocyanin production in a recombinant strain P. aeruginosa PS39-phzMS created in previous research. In addition, the process of extraction of pyocyanin was also investigated to select a proper applied solvent for recovering a high amount of pyocyanin as well as its quality.
Methodology and results:
The pyocyanin purification has based on solvent. Among six tested solvents for extracting pyocyanin out of bacterial broth, two out of six recovered a significant amount of pyocyanin, namely dichloromethane and chloroform, in which chloroform showed a higher pyocyanin yield (25.27 ± 1.02 µg/mL) than dichloromethane (20.26 ± 0.88 µg/mL). The thin-layer chromatography (TLC) of the extracted pyocyanin illustrated a similar to pure pyocyanin with Rf of 0.72 and no mark of other impurity metabolites. The UV-Vis spectra showed a similar peak at 520 nm with pure pyocyanin and the highest peak at 274 nm. Each single culture parameter was studied for the maximal production of pyocyanin. Next, a pyocyanin-producing GM medium was modified on the base of the KingA to find the relative capacity to biosynthesize high pyocyanin yield in P. aeruginosa PS39-phzMS. The results showed that pyocyanin production was the highest in optimal culture conditions, at 30 °C, pH 8, 120 h and agitation of 200 rpm. In the combination of culture condition with the GM, pyocyanin was created at the highest amount of 49.57 µg/mL.
Conclusion, significance and impact of study
Based on the obtained results of the study, a pyocyanin-producing procedure was optimized, which suggests a promising application to scale-up pyocyanin production by the P. aeruginosa PS39-phzMS.
5.Timing and Predictors of Recanalization After Anticoagulation in Cerebral Venous Thrombosis
Setareh SALEHI OMRAN ; Liqi SHU ; Allison CHANG ; Neal S. PARIKH ; Adeel S. ZUBAIR ; Alexis N. SIMPKINS ; Mirjam R. HELDNER ; Arsany HAKIM ; Sami Al KASAB ; Thanh NGUYEN ; Piers KLEIN ; Eric D. GOLDSTEIN ; Maria Cristina VEDOVATI ; Maurizio PACIARONI ; David S. LIEBESKIND ; Shadi YAGHI ; Shawna CUTTING
Journal of Stroke 2023;25(2):291-298
Background:
and Purpose Vessel recanalization after cerebral venous thrombosis (CVT) is associated with favorable outcomes and lower mortality. Several studies examined the timing and predictors of recanalization after CVT with mixed results. We aimed to investigate predictors and timing of recanalization after CVT.
Methods:
We used data from the multicenter, international AntiCoagulaTION in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT) study of consecutive patients with CVT from January 2015 to December 2020. Our analysis included patients that had undergone repeat venous neuroimaging more than 30 days after initiation of anticoagulation treatment. Prespecified variables were included in univariate and multivariable analyses to identify independent predictors of failure to recanalize.
Results:
Among the 551 patients (mean age, 44.4±16.2 years, 66.2% women) that met inclusion criteria, 486 (88.2%) had complete or partial, and 65 (11.8%) had no recanalization. The median time to first follow-up imaging study was 110 days (interquartile range, 60–187). In multivariable analysis, older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03–1.07), male sex (OR, 0.44; 95% CI, 0.24–0.80), and lack of parenchymal changes on baseline imaging (OR, 0.53; 95% CI, 0.29–0.96) were associated with no recanalization. The majority of improvement in recanalization (71.1%) occurred before 3 months from initial diagnosis. A high percentage of complete recanalization (59.0%) took place within the first 3 months after CVT diagnosis.
Conclusion
Older age, male sex, and lack of parenchymal changes were associated with no recanalization after CVT. The majority recanalization occurred early in the disease course suggesting limited further recanalization with anticoagulation beyond 3 months. Large prospective studies are needed to confirm our findings.
6.Anesthetic Management and Outcomes of Endovascular Treatment of Basilar Artery Occlusion: Results From the ATTENTION Registry
Chunrong TAO ; Guangxiong YUAN ; Pengfei XU ; Hao WANG ; Peiyang ZHOU ; Tingyu YI ; Kai LI ; Tao CUI ; Jun GAO ; Rui LI ; Jun SUN ; Chao ZHANG ; Li WANG ; Tianlong LIU ; Jianlong SONG ; Yamei YIN ; Thanh N. NGUYEN ; Qing LI ; Wei HU
Journal of Stroke 2023;25(3):399-408
Background:
and Purpose To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities.
Methods:
This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups.
Results:
Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]).
Conclusion
In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.
7.Update of Anticoagulation Use in Cardioembolic Stroke With a Special Reference to Endovascular Treatment
Apostolos SAFOURIS ; Klearchos PSYCHOGIOS ; Lina PALAIODIMOU ; Peter OROSZ ; George MAGOUFIS ; Odysseas KARGIOTIS ; Aikaterini THEODOROU ; Theodore KARAPANAYIOTIDES ; Stavros SPILIOPOULOS ; Sándor NARDAI ; Amrou SARRAJ ; Thanh N. NGUYEN ; Shadi YAGHI ; Silke WALTER ; Simona SACCO ; Guillaume TURC ; Georgios TSIVGOULIS
Journal of Stroke 2024;26(1):13-25
Cardioembolic stroke is a major cause of morbidity, with a high risk of recurrence, and anticoagulation represents the mainstay of secondary stroke prevention in most patients. The implementation of endovascular treatment in routine clinical practice complicates the decision to initiate anticoagulation, especially in patients with early hemorrhagic transformation who are considered at higher risk of hematoma expansion. Late hemorrhagic transformation in the days and weeks following stroke remains a potentially serious complication for which we still do not have any established clinical or radiological prediction tools. The optimal time to initiate therapy is challenging to define since delaying effective secondary prevention treatment exposes patients to the risk of recurrent embolism. Consequently, there is clinical equipoise to define and individualize the optimal timepoint to initiate anticoagulation combining the lowest risk of hemorrhagic transformation and ischemic recurrence in cardioembolic stroke patients. In this narrative review, we will highlight and critically outline recent observational and randomized relevant evidence in different subtypes of cardioembolic stroke with a special focus on anticoagulation initiation following endovascular treatment. We will refer mainly to the commonest cause of cardioembolism, non-valvular atrial fibrillation, and examine the possible risk and benefit of anticoagulation before, during, and shortly after the acute phase of stroke. Other indications of anticoagulation after ischemic stroke will be briefly discussed. We provide a synthesis of available data to help clinicians individualize the timing of initiation of oral anticoagulation based on the presence and extent of hemorrhagic transformation as well as stroke severity.
8.Endovascular versus Medical Management of Acute Basilar Artery Occlusion: A Systematic Review and Meta-Analysis of the Randomized Controlled Trials
Mohamad ABDALKADER ; Stephanos FINITSIS ; Chuanhui LI ; Wei HU ; Xinfeng LIU ; Xunming JI ; Xiaochuan HUO ; Fana ALEMSEGED ; Zhongming QIU ; Daniel STRBIAN ; Volker PUETZ ; James E. SIEGLER ; Shadi YAGHI ; Kaiz ASIF ; Piers KLEIN ; Yuyou ZHU ; Bruce C.V. CAMPBELL ; Hui-Sheng CHEN ; Simon NAGEL ; Georgios TSIVGOULIS ; Zhongrong MIAO ; Raul G. NOGUEIRA ; Tudor G. JOVIN ; Wouter J. SCHONEWILLE ; Thanh N. NGUYEN ;
Journal of Stroke 2023;25(1):81-91
Background:
and Purpose The optimal management of patients with acute basilar artery occlusion (BAO) is uncertain. We aimed to evaluate the safety and efficacy of endovascular thrombectomy (EVT) compared to medical management (MM) for acute BAO through a meta-analysis of randomized controlled trials (RCTs).
Methods:
We performed a systematic review and meta-analysis of RCTs of patients with acute BAO. We analyzed the pooled effect of EVT compared to MM on the primary outcome (modified Rankin Scale [mRS] of 0–3 at 3 months), secondary outcome (mRS 0–2 at 3 months), symptomatic intracranial hemorrhage (sICH), and 3-month mortality rates. For each study, effect sizes were computed as odds ratios (ORs) with random effects and Mantel-Haenszel weighting.
Results:
Four RCTs met inclusion criteria including 988 patients. There were higher odds of mRS of 0-3 at 90 days in the EVT versus MM group (45.1% vs. 29.1%, OR 1.99, 95% confidence interval [CI] 1.04–3.80; P=0.04). Patients receiving EVT had a higher sICH compared to MM (5.4% vs. 0.8%, OR 7.89, 95% CI 4.10–15.19; P<0.01). Mortality was lower in the EVT group (35.5% vs. 45.1%, OR 0.64, 95% CI 0.42–0.99; P=0.05). In an analysis of two trials with BAO patients and National Institutes of Health Stroke Scale (NIHSS) <10, there was no difference in 90-day outcomes between EVT versus MM.
Conclusion
In this systematic review and meta-analysis, EVT was associated with favorable outcome and decreased mortality in patients with BAO up to 24 hours from stroke symptoms compared to MM. The treatment effect in BAO patients with NIHSS <10 was less certain. Further studies are of interest to evaluate the efficacy of EVT in basilar occlusion patients with milder symptoms.
9.Borderzone Infarcts and Recurrent Cerebrovascular Events in Symptomatic Intracranial Arterial Stenosis: A Systematic Review and Meta-Analysis
Saurav DAS ; Liqi SHU ; Rebecca J. MORGAN ; Asghar SHAH ; Fayez H. FAYAD ; Eric D. GOLDSTEIN ; Dalia CHAHIEN ; Benton MAGLINGER ; Satish Kumar BOKKA ; Cory OWENS ; Mehdi ABBASI ; Alexandra KVERNLAND ; James E. SIEGLER ; Brian Mac GRORY ; Thanh N. NGUYEN ; Karen FURIE ; Pooja KHATRI ; Eva MISTRY ; Shyam PRABHAKARAN ; David S. LIEBESKIND ; Jose G. ROMANO ; Adam de HAVENON ; Lina PALAIODIMOU ; Georgios TSIVGOULIS ; Shadi YAGHI
Journal of Stroke 2023;25(2):223-232
Background:
and Purpose Intracranial arterial stenosis (ICAS)-related stroke occurs due to three primary mechanisms with distinct infarct patterns: (1) borderzone infarcts (BZI) due to impaired distal perfusion, (2) territorial infarcts due to distal plaque/thrombus embolization, and (3) plaque progression occluding perforators. The objective of the systematic review is to determine whether BZI secondary to ICAS is associated with a higher risk of recurrent stroke or neurological deterioration.
Methods:
As part of this registered systematic review (CRD42021265230), a comprehensive search was performed to identify relevant papers and conference abstracts (with ≥20 patients) reporting initial infarct patterns and recurrence rates in patients with symptomatic ICAS. Subgroup analyses were performed for studies including any BZI versus isolated BZI and those excluding posterior circulation stroke. The study outcome included neurological deterioration or recurrent stroke during follow-up. For all outcome events, corresponding risk ratios (RRs) and 95% confidence intervals (95% CI) were calculated.
Results:
A literature search yielded 4,478 records with 32 selected during the title/abstract triage for full text; 11 met inclusion criteria and 8 studies were included in the analysis (n=1,219 patients; 341 with BZI). The meta-analysis demonstrated that the RR of outcome in the BZI group compared to the no BZI group was 2.10 (95% CI 1.52–2.90). Limiting the analysis to studies including any BZI, the RR was 2.10 (95% CI 1.38–3.18). For isolated BZI, RR was 2.59 (95% CI 1.24–5.41). RR was 2.96 (95% CI 1.71–5.12) for studies only including anterior circulation stroke patients.
Conclusion
This systematic review and meta-analysis suggests that the presence of BZI secondary to ICAS may be an imaging biomarker that predicts neurological deterioration and/or stroke recurrence.
10.Global Impact of the COVID-19 Pandemic on Cerebral Venous Thrombosis and Mortality
Thanh N. NGUYEN ; Muhammad M. QURESHI ; Piers KLEIN ; Hiroshi YAMAGAMI ; Mohamad ABDALKADER ; Robert MIKULIK ; Anvitha SATHYA ; Ossama Yassin MANSOUR ; Anna CZLONKOWSKA ; Hannah LO ; Thalia S. FIELD ; Andreas CHARIDIMOU ; Soma BANERJEE ; Shadi YAGHI ; James E. SIEGLER ; Petra SEDOVA ; Joseph KWAN ; Diana Aguiar de SOUSA ; Jelle DEMEESTERE ; Violiza INOA ; Setareh Salehi OMRAN ; Liqun ZHANG ; Patrik MICHEL ; Davide STRAMBO ; João Pedro MARTO ; Raul G. NOGUEIRA ;
Journal of Stroke 2024;26(1):129-129