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POST-SARS-COV-2-VACCINATION CEREBRAL VENOUS SINUS THROMBOSIS: AN ANALYSIS OF CASES NOTIFIED TO THE EUROPEAN MEDICINES AGENCY
Abstract
Background and Aims
Cerebral venous sinus thrombosis (CVST) has been described after vaccination against SARS-CoV-2. We report clinical characteristics of 213 post-vaccination CVST cases notified to the European Medicines Agency (EMA).
Methods
Data on Adverse Drug Reactions (ADRs) after SARS-CoV-2 vaccination notified until 8 April 2021 under the Medical Dictionary for Regulatory Activities Term ‘Central nervous system vascular disorders’ were obtained from the EudraVigilance database. We compared post-vaccination CVST to 100 European patients with CVST from before the COVID-19 pandemic (2015-2018) derived from the International CVST Consortium.
Results
We identified 213 CVST cases: 187 after ChAdOx1 nCov-19 vaccination and 26 after a mRNA vaccine (25 BNT162b2 and 1 mRNA-1273).. Thrombocytopenia was reported in 107 CVST cases (57%, 95%CI 50-64%) in the ChAdOx1 nCov-19 group, in none in the mRNA vaccine group (0%, 95%CI 0-13%), and in 7 (7%, 95%CI 3-14%) in the pre-COVID-19 group. In the ChAdOx1 nCov-19 group, there were 39 (21%) reported COVID-19 PCR tests performed within 30 days of CVST symptom onset, all were negative. Of the 117 patients with a reported outcome in the ChAdOx1 nCov-19 group, 44 (38%, 95%CI 29-47%) had died, compared to 2/10 (20%, 95%CI 6-51%) in the mRNA vaccine group and 3/100 (3%, 95%CI 1-8%) in the pre-COVID-19 group. Mortality among patients with thrombocytopenia in the ChAdOx1 nCov-19 group was 49% (95%CI 39-60%).
Conclusions
Analysis of EMA data shows that CVST occurring after ChAdOx1 nCov-19 vaccination has a clinical profile distinct from CVST unrelated to vaccination. Thrombocytopenia was associated only with CVST after ChAdOx1 nCov-19 vaccination.
STROKE IN COVID-19-POSITIVE PATIENTS: HISTOPATHOLOGICAL FINDINGS
Abstract
Background and Aims
Аccording to WHO as of 17 May 2021, there have been 162 704 139 confirmed cases of COVID-19, including 3 374 052 deaths in the world. The last updated on May 17, 2021 for Ukraine indicates that coronavirus cases were 2,156,000 and deaths were 48,184. Stroke is the most difficult neurological disorder associated with COVID-19. The aim of this study was to assess the histopathological findings of the brain tissue in patients who died from complications of COVID-19 and stroke.
Methods
All patients died in Lviv regional and city hospitals from complications of COVID-19 and had a positive test for SARS-CoV-2 detected by qRT-PCR reaction. Patients were autopsied between March 2020 and May 2021, information from the autopsy protocol included macroscopic and microscopic characteristics of brain and general autopsy findings. We used common histological methods of staining with hematoxylin and eosin.
Results
The post-mortem study included 89 cases. The patients had a median age of 67 years (range, 21-97 years), 53,93% men (n=48). The majority of patients (60,67%, n=54) had hypertension, while 29 (32,58%) had type 2 diabetes mellitus and hypertension. The large vessel ischemic strokes with colliquation necrosis, inflammation infiltrates, acute hypoxic neurons and marked edema diagnosed in 3 (3,37%) COVID-19 patients, without prior history of stroke, 2 (2,25%) COVID-19 patients had evidence of intracranial hemorrhage, one of intracranial hemorrhages occurred as a secondary transformation of an ischemic infarct.
Conclusions
Stroke is the difficult neurological disorder associated with COVID-19, hypertension and diabetes are risk factors for severe COVID-19 course or poor outcome.
THE DETRIMENTAL IMPACT OF NOT MAINTAINING ACCESS TO STROKE UNITS DURING THE COVID-19 PANDEMIC
Abstract
Background and Aims
Changes to hospital resourcing related to acute stroke care have occurred as a by-product of the COVID-19 pandemic. There is uncertainty on the impacts this has had on the quality of care. We aimed to compare the provision of acute stroke care provided in stroke units with alternate ward settings during the pandemic.
Methods
Patients admitted with stroke or transient ischaemic attack from 61 hospitals contributing data to the Australian Stroke Clinical Registry in 2019 and 2020 were included. Interrupted time series analysis was conducted to assess trends in the provision of therapies before and after two critical pandemic time points in Australia: the first wave (starting 1/3/2020); and the second wave (between 9/7/2020-20/10/2020).
Results
There were 19,164 admissions in 2019 and 19,131 admissions in 2020 included, with no differences in age and sex between years (mean age 73 years, 56% male). Fewer patients were provided treatment in a stroke unit in 2020 compared to 2019 (72% vs 77%, p<0.001). There were greater declines in the provision of hyperacute aspirin and secondary prevention medications at discharge in alternate wards than stroke units during the second wave (between 0.41% and 1.31% per week). Provision of mobilisation and swallow screening/assessment declined in alternate wards only. Provision of care planning at discharge improved in alternate wards relative to stroke units by 0.49% per week during the first wave and 1.14% per week during the second wave.
Conclusions
Maintaining access to stroke units is paramount to ensuring best practice care even during a pandemic.
COL4A1 VARIANTS IN CHINESE PATIENTS WITH INTRACEREBRAL HEMORRHAGE
Abstract
Background and Aims
In genome-wide association study, COL4A1 was reported to be associated with the risk or recurrence of intracerebral hemorrhage (ICH). The purpose of this study is to screen the COL4A1 variants in Chinese ICH patients and to summarize the relationship between the variants and clinical characteristics.
Methods
It was a prospective multicenter cohort study that included patients with ICH from 21 hospitals in China from 2015 to 2019. Hemorrhage due to brain trauma, arteriovenous malformations, hemorrhagic tumor and hemorrhagic transformation were excluded. Targeted sequencing of a 65-gene panel including COL4A1 was performed to detect all the exons and ±10 bp splicing sites.
Results
Totally, 568 patients were included in this study. For rare variants with minimum allele frequency (MAF) <1%, 6 missense variants and 6 suspicious splice site variants, absent in 573 healthy controls, were found in 18 patients. Compared with ChinaMAP public database, A allele in rs199822852 was significantly associated with the risk of ICH (p<0.001, OR 6.727 (95%CI 3.00-15.0)). For the nine SNP loci with MAF>5%, no statistical difference was found in the genotype distribution compared with controls. There was no significant difference in age of onset, hematoma volume and location, ratio of recurrent ICH and death at 1-year follow-up between patients with or without rare variants.
Conclusions
Rare variants in COL4A1 accounted for 3.17% (18/568) in Chinese ICH patients. This study indicated A allele in rs199822852 might increase the risk of ICH, while COL4A1 rare variants might not be related to the clinical phenotype.
REGRESSION OF WHITE MATTER HYPERINTENSITY LESIONS IN CEREBRAL SMALL VESSEL DISEASE
Abstract
Background and Aims
White matter hyperintensities (WMHs) are a radiological hallmark of cerebral small vessel disease (SVD). Previous studies have found that whole brain WMH burden can reduce over time, but the extent of lesion regression and the factors that drive it are not fully understood. We aimed to assess WMH regression in three SVD cohorts.
Methods
Participants were from the SCANS observational study (n=99; MRI at 0/1/2/3 years) and the PRESERVE trial (intensive blood pressure lowering in SVD; standard treatment arm n=42; MRI at 0/1 year) and had symptomatic lacunar infarcts with moderate WMH burden at baseline (Fazekas score>=2). WMHs in SCANS were calculated using a two-step pipeline mapping individual images to a participant average and then warping to a group average space. WMHs in PRESERVE were calculated using a semi-automatic contouring program with pre- and post-treatment FLAIR images marked in parallel (blinded to timepoint). Regression was defined as WMH reduction >0.25cc between scans.
Results
WMH volume at baseline in SCANS was 45.8cc and the mean change between scans was 4.5+/-6.3cc; no subjects showed regression. WMH at baseline in PRESERVE was 31.0cc and the mean change between scans was 5.9+/-6.0cc); 6 subjects showed regression. Compared to non-regressors there were no significant differences in age, sex, baseline WMH volume, lacune number or brain volume.
Conclusions
Few participants showed WMH regression. To test whether this is due to statistical/imaging factors or SVD severity, we will apply the method used to quantify WMHs in PRESERVE to a third cohort with less severe SVD - the RUN-DMC study (n=276).
STROKELINE OUTREACH – A NEED FOR CONTINUITY OF STROKE CARE EXTENDING BEYOND COVID19
Abstract
Background and Aims
In anticipation of care disruption for survivors of stroke from the coronavirus pandemic (COVID-19), Stroke Foundation developed StrokeLine Outreach to ensure continuity of care for Queensland survivors of stroke supported by a Queensland Government grant.
Methods
StrokeLine Outreach was a one-year outbound telephone service targeting vulnerable and at-risk survivors of stroke and carers referred at discharge from acute hospital services. It was delivered by Stroke Foundation health professionals and built on established Stroke Foundation services. The program focus was health and medication management, understanding and managing the impacts of stroke, stroke risk factors, secondary prevention, and mental health risk assessment (using Patient Health Questionnaire-4 - PHQ-4). This was achieved through the provision of information, resources and services including connecting in with general practioners, allied health, community services, hospital services and support groups and mental health services.
Results
10 hospitals participated with 551 referrals. 69% completed the service. 31% of survivors of stroke reported significant issues on discharge and 25% reported difficulties coping or not coping post stroke. Of those screened for mental health issues 72% were at low risk for developing anxiety and depression, 14% at medium risk and 14% scored at high-risk. Eighteen cases required extensive support.
Conclusions
We identified that post hospital discharge continuity of care for survivors of stroke is a pressing area of need with mental health an important consideration. The program demonstrated an existing and ongoing need for the StrokeLine Outreach service given the less than anticipated impact of COVID-19 in Queensland.
OBSTRUCTIVE SLEEP APNEA IS ASSOCIATED WITH MARKERS OF CEREBRAL SMALL VESSEL DISEASE IN A DOSE-DEPENDENT MANNER: A SYSTEMATIC REVIEW AND META-ANALYSIS
Abstract
Background and Aims
Cerebral small vessel disease (CSVD) manifests on neuroimaging as white matter hyperintensities (WMH), lacunes, or cerebral microbleeds (CMBs) and is a major contributor to dementia, stroke and incident death. Obstructive sleep apnea (OSA) may disrupt endothelial cell metabolism and repair, thus increasing the risk of CSVD. This systematic review/meta-analysis aims to elucidate whether OSA severity increases the likelihood of exhibiting CSVD.
Methods
This review was registered on PROSPERO and conducted in accordance with PRISMA standards. We searched Medline, Embase and Cochrane for studies reporting associations between OSA and CSVD. A random-effects model was used to meta-analyze unadjusted odds ratios (OR) derived from event rates. CSVD prevalence was compared between groups with no OSA (apnea-hypopnea index [AHI]<5), mild OSA (5≤AHI<15), moderate-severe OSA (AHI≥15) and severe OSA (AHI≥30). Study quality was assessed using the Newcastle-Ottawa Scale.
Results
Thirty-two observational studies were included: 24 reported effect sizes for WMHs, 11 for lacunes and 4 for CMBs. Eighteen studies were rated as “high-quality”. Upon pooling ORs, we found OSA severity to be significantly associated with WMHs. Compared to patients without OSA, the odds of possessing WMHs were 1.7[95%CI 0.9;3.6] in mild OSA, 3.9[2.7;5.5] in moderate-severe OSA and 4.3[1.9;9.6] in severe OSA (Figure 1). We also observed potential, albeit nonsignificant, dose responses between OSA severity and lacunes or CMBs amidst heterogeneous data.
Conclusions
This meta-analysis is the first to elucidate a potential dose-dependent relationship between OSA severity and WMH burden. Our findings invite future research to explore the role of OSA treatment in stabilizing or ameliorating CSVD progression.