[Cerebral venous sinus thrombosis presenting transient ischemic attack after recovery from COVID-19 with Graves' disease and IgG4-related ophthalmic disease: a case report].

A 57-year-old man presented with headache, transient right upper extremity weakness and numbness one month after recovery from coronavirus disease 2019 (COVID-19). His medical history included Graves' disease and IgG4-related ophthalmic disease. He had been administered prednisolone. His weakness and numbness were transient and not present on admission. Contrast-enhanced CT and MRI of the head showed thrombi in the superior sagittal sinus, right transverse sinus, sigmoid sinus, and the right internal jugular vein. Digital subtraction angiography showed occlusion at the same sites and mild perfusion delay in the left frontoparietal lobe. We diagnosed the patient with cerebral venous sinus thrombosis and treated him with anticoagulation. The thrombi partially regressed three months later, and perfusion delay became less noticeable. Cerebral venous sinus thrombosis is an important complication of COVID-19. Patients with predisposing factors, including Graves' disease and IgG4-related ophthalmic disease, may be at increased risk of developing cerebral venous sinus thrombosis even after recovery from COVID-19.

[COVID-19-Induced Cerebrovascular Disease].

As the number of COVID-19 cases continues to rapidly increase worldwide, a corresponding increase in COVID-19-induced neurological complications is being observed in clinical practice. COVID-19 is shown to trigger a pro-thrombotic state, which increases the risk of ischemic stroke. However, the incidence of COVID-19-induced ischemic stroke in 2022 was lower than that observed during the early stages of the pandemic. In this chapter, we describe the association between COVID-19 and stroke and the pathophysiology and prognosis of stroke in patients with COVID-19, together with a review of the latest literature.

Impact of COVID-19 on the Volume of Acute Stroke Admissions: A Nationwide Survey in Japan.

This study aimed to measure the impact of the COVID-19 pandemic on the volumes of annual stroke admissions compared with those before the pandemic in Japan. We conducted an observational, retrospective nationwide survey across 542 primary stroke centers in Japan. The annual admission volumes for acute stroke within 7 days from onset between 2019 as the pre-pandemic period and 2020 as the pandemic period were compared as a whole and separately by months during which the epidemic was serious and prefectures of high numbers of infected persons. The number of stroke patients declined from 182,660 in 2019 to 178,083 in 2020, with a reduction rate of 2.51% (95% confidence interval [CI], 2.58%-2.44%). The reduction rates were 1.92% (95% CI, 1.85%-2.00%; 127,979-125,522) for ischemic stroke, 3.88% (95% CI, 3.70%-4.07%, 41,906-40,278) for intracerebral hemorrhage, and 4.58% (95% CI, 4.23%-4.95%; 13,020-12,424) for subarachnoid hemorrhage. The admission volume declined by 5.60% (95% CI, 5.46%-5.74%) during the 7 months of 2020 when the epidemic was serious, whereas it increased in the remaining 5 months (2.01%; 95% CI, 1.91%-2.11%). The annual decline in the admission volume was predominant in the five prefectures with the largest numbers of infected people per million population (4.72%; 95% CI, 4.53%-4.92%). In conclusion, the acute stroke admission volume declined by 2.51% in 2020 relative to 2019 in Japan, especially during the months of high infection, and in highly infected prefectures. Overwhelmed healthcare systems and infection control practices may have been associated with the decline in the stroke admission volume during the COVID-19 pandemic.

Safety and Outcomes of Intravenous Thrombolytic Therapy in Ischemic Stroke Patients with COVID-19: CASCADE Initiative.

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19.

Evaluation of Workflow Delays in Stroke Reperfusion Therapy: A Comparison between the Year-Long Pre-COVID-19 Period and the with-COVID-19 Period.

AIM: We evaluated the delay in stroke reperfusion therapy between the pre-coronavirus disease 2019 (COVID-19) period and the with-COVID-19 period, and compared this delay between each phase of the with-COVID-19 period. METHODS: Patients with acute ischemic stroke (AIS) undergoing intravenous thrombolysis and/or mechanical thrombectomy were selected from our single-center prospective registry. The time to perform reperfusion therapy were compared between patients admitted from March 2019 to February 2020 (pre-COVID-19 group) and those from March 2020 to February 2021 (with-COVID-19 group). Patients in the with-COVID-19 group were further divided into three 4-month-long subgroups (first-phase: March to June 2020; second-phase: July to October 2020; third-phase: November 2020 to February 2021), and the time delay of reperfusion therapy were compared between these subgroups. RESULTS: Of 1,260 patients with AIS hospitalized in the study period, 265 patients were examined. Compared with the pre-COVID-19 group (133 patients; median age, 79 years), the with-COVID-19 group (132 patients; median age, 79 years) had a longer median door-to-imaging time (25 min vs. 27 min, P=0.04), and a longer door-to-groin puncture time (65 min vs. 72 min, P=0.02). In the three 4-month-long subgroups, the median door-to-needle time (49 min, 43 min, and 38 min, respectively; P=0.04) and door-to-groin puncture time (83 min, 70 min, and 61 min, P＜0.01, respectively) decreased significantly during the with-COVID-19 period. CONCLUSIONS: The delay in reperfusion therapy increased during the with-COVID-19 period compared with the pre-COVID-19 period. However, the door-to-needle time and door-to-groin puncture time decreased as time elapsed during the with-COVID-19 period. CLINICALTRIALS: gov Identifier: NCT02251665.

Adrenomedullin: A vasoactive agent for sporadic and hereditary vascular cognitive impairment.

Adrenomedullin (AM) is an endogenous peptide mainly secreted from endothelial cells, which has multiple physiological actions such as anti-inflammation, vasodilation, vascular permeability regulation and angiogenesis. Blood AM levels are upregulated in a variety of pathological states including sepsis, severe COVID-19, acute ischemic stroke and vascular cognitive impairment with white matter changes, likely serving as a compensatory biological defense response against infection and ischemia. AM is currently being tested in clinical trials for ulcerative colitis, Crohn's disease, severe COVID-19 for its anti-inflammatory properties and in ischemic stroke for its additional angiogenic action. AM has been proposed as a therapeutic option for vascular cognitive impairment as its arteriogenic and angiogenic properties are thought to contribute to a slowing of cognitive decline in mice after chronic cerebral hypoperfusion. As AM promotes differentiation of oligodendrocyte precursor cells into mature oligodendrocytes under hypoxic conditions, AM could also be used in the treatment of CADASIL, where reduced oxygen delivery is thought to lead to the death of hypoxia-prone oligodendrocytes. AM therefore holds potential as an innovative therapeutic drug, which may regenerate blood vessels, while controlling inflammation in cerebrovascular diseases.

Stroke Care Trends During COVID-19 Pandemic in Zanjan Province, Iran. From the CASCADE Initiative: Statistical Analysis Plan and Preliminary Results.

BACKGROUND: The emergence of the COVID-19 pandemic has significantly impacted global healthcare systems and this may affect stroke care and outcomes. This study examines the changes in stroke epidemiology and care during the COVID-19 pandemic in Zanjan Province, Iran. METHODS: This study is part of the CASCADE international initiative. From February 18, 2019, to July 18, 2020, we followed ischemic and hemorrhagic stroke hospitalization rates and outcomes in Valiasr Hospital, Zanjan, Iran. We used a Bayesian hierarchical model and an interrupted time series analysis (ITS) to identify changes in stroke hospitalization rate, baseline stroke severity [measured by the National Institutes of Health Stroke Scale (NIHSS)], disability [measured by the modified Rankin Scale (mRS)], presentation time (last seen normal to hospital presentation), thrombolytic therapy rate, median door-to-needle time, length of hospital stay, and in-hospital mortality. We compared in-hospital mortality between study periods using Cox-regression model. RESULTS: During the study period, 1,026 stroke patients were hospitalized. Stroke hospitalization rates per 100,000 population decreased from 68.09 before the pandemic to 44.50 during the pandemic, with a significant decline in both Bayesian [Beta: -1.034; Standard Error (SE): 0.22, 95% CrI: -1.48, -0.59] and ITS analysis (estimate: -1.03, SE = 0.24, p < 0.0001). Furthermore, we observed lower admission rates for patients with mild (NIHSS < 5) ischemic stroke (p < 0.0001). Although, the presentation time and door-to-needle time did not change during the pandemic, a lower proportion of patients received thrombolysis (-10.1%; p = 0.004). We did not see significant changes in admission rate to the stroke unit and in-hospital mortality rate; however, disability at discharge increased (p < 0.0001). CONCLUSION: In Zanjan, Iran, the COVID-19 pandemic has significantly impacted stroke outcomes and altered the delivery of stroke care. Observed lower admission rates for milder stroke may possibly be due to fear of exposure related to COVID-19. The decrease in patients treated with thrombolysis and the increased disability at discharge may indicate changes in the delivery of stroke care and increased pressure on existing stroke acute and subacute services. The results of this research will contribute to a similar analysis of the larger CASCADE dataset in order to confirm findings at a global scale and improve measures to ensure the best quality of care for stroke patients during the COVID-19 pandemic.