Publications by authors named "Georgios Tsivgoulis"

494 Publications

Association of Psychometric Indices and Normal Electrodiagnostic Studies in Referral for Suspected Carpal Tunnel Syndrome.

In Vivo 2021 May-Jun;35(3):1791-1797

Second Department of Psychiatry, Medical School, National and Kapodistrian University of Athens, Attikon University General Hospital, Athens, Greece.

Background/aim: The aim of this study was to investigate psychometric indices and their association with electrodiagnostic studies (EDX).

Patients And Methods: A total of 100 patients referred for EDX testing of the upper limbs were prospectively enrolled. Demographic data, laboratory test results, referral physician specialty, main symptom, WHODAS 2.0-12 item version, Hospital Anxiety and Depression Scale (HADS), Boston Carpal Tunnel Questionnaire (BCTQ) and a Numeric Rating Scale (NRS) indicating the extent of their discomfort were collected.

Results: Normal EDX results were elicited from 56% of patients. Only the presence of numbness in the right hand, pain in the left hand and older age were significantly associated with an abnormal EDX result. The more depressed and anxious the patients were, the more they scored on psychometric scales.

Conclusion: The large prevalence of normal EDX studies raises the issue of unnecessary referrals. A proportion of patients are referred only according to their reported symptoms. Psychological factors affect the way a person expresses physical discomfort, leading to unnecessary EDX referrals and inevitably with normal results.
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http://dx.doi.org/10.21873/invivo.12439DOI Listing
February 2021

Clinical and Neuroimaging Outcomes of Direct Thrombectomy vs Bridging Therapy in Large Vessel Occlusion: Analysis of the SELECT Cohort Study.

Neurology 2021 Apr 19. Epub 2021 Apr 19.

The University of Tennessee Health Science Center, Memphis, USA.

Objective: To evaluate the comparative safety and efficacy of direct endovascular thrombectomy(dEVT) compared to bridging therapy(BT:IV-tPA+EVT) and assess if BT potential benefit relates to stroke severity, size and initial presentation to EVT vs. non-EVT center.

Methods: In a prospective multicenter cohort-study of imaging selection for endovascular thrombectomy[SELECT], anterior-circulation large vessel occlusion (LVO) patients presenting to EVT-capable centers within 4.5hours from last-known-well were stratified into BT vs. dEVT. The primary outcome was 90-day functional independence[modified Rankin Scale(mRS)=0-2]. Secondary outcomes included a shift across 90-day mRS grades, mortality, symptomatic intracranial hemorrhage. We also performed subgroup-analyses according to initial presentation to EVT-capable center (direct versus transfer), stroke severity and baseline infarct core volume.

Results: We identified 226 LVOs (54%:men, mean age:65.6±14.6years, median NIHSS-score: 17, 28% received dEVT). Median time from arrival to groin-puncture did not differ in BT-patients when presenting directly[dEVT:1.43 (IQR=1.13-1.90) hours vs. BT:1.58(IQR=1.27-2.02)hours,p=0.40] or transferred to EVT-capable centers[dEVT:1.17 (IQR: 0.90-1.48) hours vs. BT:1.27 (IQR: 0.97-1.87) hours,p=0.24]. BT was associated with higher odds of 90-day functional independence (57% vs. 44%,aOR=2.02,95%CI:1.01-4.03,p=0.046) and functional improvement (adjusted cOR=2.06,95%CI:1.18-3.60,p=0.011), and lower likelihood of 90-day mortality (11% vs. 23%,aOR: 0.20,95%CI:0.07-0.58,p=0.003). No differences in any other outcomes were detected. In subgroup-analyses, BT patients with baseline NIHSS-scores<15 had higher functional independence likelihood compared to dEVT (aOR=4.87,95%CI:1.56-15.18,p=0.006); this association was not evident for patients with NIHSS-scores≥15 (aOR=1.05,95%CI:0.40-2.74,p=0.92). Similarly, functional outcomes improvements with BT were detected in patients with core volume strata (Ischemic core <50cc: aOR: 2.10, 95% CI:1.02-4.33, p=0.044 vs ischemic core ≥50cc: aOR: 0.41,95% CI:0.01-16.02,p=0.64) and transfer status (transferred: aOR: 2.21,95% CI:0.93-9.65,p=0.29 vs direct to EVT center: aOR:1.84,95%CI:0.80-4.23,p=0.15).

Conclusions: Bridging therapy appears to be associated with better clinical outcomes, especially with milder NIHSS-scores, smaller presentation core volumes and those who were "dripped and shipped". We did not observe any potential benefit of bridging therapy in patients with more severe strokes.

Classification Of Evidence: This study provides Class III evidence that for patients with ischemic stroke from anterior-circulation LVO within 4.5 hours from last-known-well, bridging therapy compared to direct endovascular thrombectomy leads to better 90-day functional outcomes.
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http://dx.doi.org/10.1212/WNL.0000000000012063DOI Listing
April 2021

Stroke in SARS-CoV-2 Infection: A Pictorial Overview of the Pathoetiology.

Front Cardiovasc Med 2021 29;8:649922. Epub 2021 Mar 29.

Neurology Department, Neuroscience Institute, Geisinger Health System, Danville, PA, United States.

Since the early days of the pandemic, there have been several reports of cerebrovascular complications during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Numerous studies proposed a role for SARS-CoV-2 in igniting stroke. In this review, we focused on the pathoetiology of stroke among the infected patients. We pictured the results of the SARS-CoV-2 invasion to the central nervous system (CNS) via neuronal and hematogenous routes, in addition to viral infection in peripheral tissues with extensive crosstalk with the CNS. SARS-CoV-2 infection results in pro-inflammatory cytokine and chemokine release and activation of the immune system, COVID-19-associated coagulopathy, endotheliitis and vasculitis, hypoxia, imbalance in the renin-angiotensin system, and cardiovascular complications that all may lead to the incidence of stroke. Critically ill patients, those with pre-existing comorbidities and patients taking certain medications, such as drugs with elevated risk for arrhythmia or thrombophilia, are more susceptible to a stroke after SARS-CoV-2 infection. By providing a pictorial narrative review, we illustrated these associations in detail to broaden the scope of our understanding of stroke in SARS-CoV-2-infected patients. We also discussed the role of antiplatelets and anticoagulants for stroke prevention and the need for a personalized approach among patients with SARS-CoV-2 infection.
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http://dx.doi.org/10.3389/fcvm.2021.649922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039152PMC
March 2021

Prevalence, clinical characteristics and outcomes of Guillain-Barré syndrome spectrum associated with COVID-19: A systematic review and meta-analysis.

Eur J Neurol 2021 Apr 9. Epub 2021 Apr 9.

Second Department of Neurology, 'Attikon' University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Background And Purpose: Mounting evidence supports an association between Guillain-Barré syndrome spectrum (GBSs) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, GBSs in the setting of coronavirus disease 2019 (COVID-19) remains poorly characterized, whilst GBSs prevalence amongst COVID-19 patients has not been previously systematically evaluated using a meta-analytical approach.

Methods: A systematic review and meta-analysis of observational cohort and case series studies reporting on the occurrence, clinical characteristics and outcomes of patients with COVID-19-associated GBSs was performed. A random-effects model was used to calculate pooled estimates and odds ratios (ORs) with corresponding 95% confidence intervals (CIs), compared to non-COVID-19, contemporary or historical GBSs patients.

Results: Eighteen eligible studies (11 cohorts, seven case series) were identified including a total of 136,746 COVID-19 patients. Amongst COVID-19 patients, including hospitalized and non-hospitalized cases, the pooled GBSs prevalence was 0.15‰ (95% CI 0%-0.49‰; I  = 96%). Compared with non-infected contemporary or historical controls, patients with SARS-CoV-2 infection had increased odds for demyelinating GBSs subtypes (OR 3.27, 95% CI 1.32%-8.09%; I  = 0%). In SARS-CoV-2-infected patients, olfactory or concomitant cranial nerve involvement was noted in 41.4% (95% CI 3.5%-60.4%; I  = 46%) and 42.8% (95% CI 32.8%-53%; I  = 0%) of the patients, respectively. Clinical outcomes including in-hospital mortality were comparable between COVID-19 GBSs patients and non-infected contemporary or historical GBSs controls.

Conclusion: GBSs prevalence was estimated at 15 cases per 100,000 SARS-CoV-2 infections. COVID-19 appears to be associated with an increased likelihood of GBSs and with demyelinating GBSs variants in particular.
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http://dx.doi.org/10.1111/ene.14860DOI Listing
April 2021

Cervical duplex ultrasound for the diagnosis of giant cell arteritis with vertebral artery involvement.

J Neuroimaging 2021 Apr 5. Epub 2021 Apr 5.

Second Department of Neurology, National & Kapodistiran University of Athens, School of Medicine, "Attikon" University Hospital, Athens, Greece.

Giant cell arteritis (GCA) is a systemic inflammatory arteriopathy of medium and large-sized arteries, predominantly affecting branches of the external carotid artery. Ischemic stroke has been reported in 2.8-7% of patients diagnosed with GCA. The majority of ischemic strokes may involve the posterior circulation as a result of vertebral and/or, less frequently, of basilar artery vasculitis. Prompt diagnosis is crucial since high-dose corticosteroid treatment is highly effective in preventing the occurrence or recurrence of ischemic complications, including posterior circulation ischemic stroke in cases with vertebrobasilar involvement. Cervical duplex sonography (CDS) of the temporal arteries is a powerful diagnostic tool with high sensitivity and specificity for the diagnosis of GCA. In cases with clinical suspicion or a temporal artery ultrasonographic confirmation of GCA, a detailed evaluation of the cervical, axillary, and intracranial arteries with CDS and transcranial-duplex-sonography, respectively, should be part of the ultrasound examination protocol. Specifically, signs of extracranial vertebral artery wall inflammation ("halo" sign) and focal luminar stenoses may be accurately depicted by ultrasounds in high-risk patients or individuals with ischemic stroke attributed to GCA. In this review, we present three cases of GCA and posterior circulation ischemic complications that were initially evaluated with comprehensive neurosonology protocol and were promptly diagnosed with GCA based on the characteristic "halo" sign in the temporal and vertebral arteries. In addition, we discuss the relevant literature concerning the utility of CDS for the early diagnosis of GCA, focusing on the subtype with extracranial arterial involvement, particularly that of the vertebral arteries.
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http://dx.doi.org/10.1111/jon.12857DOI Listing
April 2021

European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke.

Eur Stroke J 2021 Mar 19;6(1):I-LXII. Epub 2021 Feb 19.

Department of Neurology, GHU Paris Psychiatrie et Neurosciences, Hopital Sainte-Anne, Université de Paris, Paris, France.

Intravenous thrombolysis is the only approved systemic reperfusion treatment for patients with acute ischaemic stroke. These European Stroke Organisation (ESO) guidelines provide evidence-based recommendations to assist physicians in their clinical decisions with regard to intravenous thrombolysis for acute ischaemic stroke. These guidelines were developed based on the ESO standard operating procedure and followed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The working group identified relevant clinical questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence, and wrote recommendations. Expert consensus statements were provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found high quality evidence to recommend intravenous thrombolysis with alteplase to improve functional outcome in patients with acute ischemic stroke within 4.5 h after symptom onset. We also found high quality evidence to recommend intravenous thrombolysis with alteplase in patients with acute ischaemic stroke on awakening from sleep, who were last seen well more than 4.5 h earlier, who have MRI DWI-FLAIR mismatch, and for whom mechanical thrombectomy is not planned. These guidelines provide further recommendations regarding patient subgroups, late time windows, imaging selection strategies, relative and absolute contraindications to alteplase, and tenecteplase. Intravenous thrombolysis remains a cornerstone of acute stroke management. Appropriate patient selection and timely treatment are crucial. Further randomized controlled clinical trials are needed to inform clinical decision-making with regard to tenecteplase and the use of intravenous thrombolysis before mechanical thrombectomy in patients with large vessel occlusion.
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http://dx.doi.org/10.1177/2396987321989865DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995316PMC
March 2021

SARS-CoV-2 Is a Culprit for Some, but Not All Acute Ischemic Strokes: A Report from the Multinational COVID-19 Stroke Study Group.

J Clin Med 2021 Mar 1;10(5). Epub 2021 Mar 1.

Neurology Department, Neuroscience Institute, Geisinger Health System, Danville, PA 17822, USA.

Background: SARS-CoV-2 infected patients are suggested to have a higher incidence of thrombotic events such as acute ischemic strokes (AIS). This study aimed at exploring vascular comorbidity patterns among SARS-CoV-2 infected patients with subsequent stroke. We also investigated whether the comorbidities and their frequencies under each subclass of TOAST criteria were similar to the AIS population studies prior to the pandemic.

Methods: This is a report from the Multinational COVID-19 Stroke Study Group. We present an original dataset of SASR-CoV-2 infected patients who had a subsequent stroke recorded through our multicenter prospective study. In addition, we built a dataset of previously reported patients by conducting a systematic literature review. We demonstrated distinct subgroups by clinical risk scoring models and unsupervised machine learning algorithms, including hierarchical K-Means (ML-K) and Spectral clustering (ML-S).

Results: This study included 323 AIS patients from 71 centers in 17 countries from the original dataset and 145 patients reported in the literature. The unsupervised clustering methods suggest a distinct cohort of patients (ML-K: 36% and ML-S: 42%) with no or few comorbidities. These patients were more than 6 years younger than other subgroups and more likely were men (ML-K: 59% and ML-S: 60%). The majority of patients in this subgroup suffered from an embolic-appearing stroke on imaging (ML-K: 83% and ML-S: 85%) and had about 50% risk of large vessel occlusions (ML-K: 50% and ML-S: 53%). In addition, there were two cohorts of patients with large-artery atherosclerosis (ML-K: 30% and ML-S: 43% of patients) and cardioembolic strokes (ML-K: 34% and ML-S: 15%) with consistent comorbidity and imaging patterns. Binominal logistic regression demonstrated that ischemic heart disease (odds ratio (OR), 4.9; 95% confidence interval (CI), 1.6-14.7), atrial fibrillation (OR, 14.0; 95% CI, 4.8-40.8), and active neoplasm (OR, 7.1; 95% CI, 1.4-36.2) were associated with cardioembolic stroke.

Conclusions: Although a cohort of young and healthy men with cardioembolic and large vessel occlusions can be distinguished using both clinical sub-grouping and unsupervised clustering, stroke in other patients may be explained based on the existing comorbidities.
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http://dx.doi.org/10.3390/jcm10050931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957755PMC
March 2021

Stopping "transient ischemic attacks" by antiplatelet withdrawal.

Neurol Res Pract 2021 Apr 1;3(1):19. Epub 2021 Apr 1.

Second Department of Neurology, National and Kapodistrian University of Athens, School of Medicine, "Attikon" University Hospital, Rimini 1, Chaidari, 12462, Athens, Greece.

Introduction: Transient ischemic attack (TIA) is considered to be an important risk factor for the development of ischemic stroke and requires complete etiopathogenic evaluation and prompt initiation of secondary prevention treatment. In addition, an accurate differential diagnosis should be performed in order to exclude other disorders mimicking TIA.

Methods: In this case report, we describe the clinical and neuroimaging evaluation and the differential diagnosis of a patient with suspected crescendo TIAs.

Results: A 79-year-old man presented with recurrent episodes of right-sided numbness over the past 7 months, despite different single and dual antiplatelet therapies that were sequentially prescribed for suspected TIAs. Brain MRI revealed cortical superficial siderosis, symmetrical periventricular leukoencephalopathy and enlarged perivascular spaces. Cerebral amyloid angiopathy was considered in the differential diagnosis of the patient. Antiplatelet withdrawal was recommended and led to complete remission of the patient's transient focal neurological episodes (TFNE) that were initially misdiagnosed as TIAs.

Discussion: Cortical superficial siderosis has been implicated as a key neuroimaging feature of cerebral amyloid angiopathy, a diagnosis which can be supported by the additional radiological findings of symmetrical white matter hyperintensities and enlarged perivascular spaces. Antiplatelet treatment in patients with cortical superficial siderosis may increase the frequency and severity of TFNE, while it increases exponentially the risk of intracerebral hemorrhage. The present case highlights that recognition of cortical superficial siderosis is crucial in the management of patients presenting with transient focal neurological symptoms that can be misdiagnosed as recurrent TIAs.
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http://dx.doi.org/10.1186/s42466-021-00117-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015043PMC
April 2021

Burden of oral anticoagulation in embolic stroke of undetermined source without atrial fibrillation.

BMC Cardiovasc Disord 2021 Mar 31;21(1):160. Epub 2021 Mar 31.

Florey Institute of Neuroscience, Melbourne, Australia.

Objective: Prevention of recurrent stroke in patients with embolic stroke of undetermined source (ESUS) is challenging. The advent of safer anticoagulation in the form of direct oral anticoagulants (DOACs) has prompted exploration of prophylactic anticoagulation for all ESUS patients, rather than anticoagulating just those with documented atrial fibrillation (AF). However, recent trials have failed to demonstrate a clinical benefit, while observing increased bleeding. We modeled the economic impact of anticoagulating ESUS patients without documented AF across multiple geographies.

Methods: CRYSTAL-AF trial data were used to assess ischaemic stroke event rates in ESUS patients confirmed AF-free after long-term monitoring. Anticipated bleeding event rates (including both minor and major bleeds) with aspirin, dabigatran 150 mg, and rivaroxaban 20 mg were sourced from published meta-analyses, whilst a 30% ischaemic stroke reduction for both DOACs was assumed. Cost data for clinical events and pharmaceuticals were collected from the local payer perspective.

Results: Compared with aspirin, dabigatran and rivaroxaban resulted in 17.9 and 29.9 additional bleeding events per 100 patients over a patient's lifetime, respectively. Despite incorporating into our model the proposed 30% reduction in ischaemic stroke risk, both DOACs were cost-additive over patient lifetime, as the costs of bleeding events and pharmaceuticals outweighed cost savings associated with the reduction in ischaemic strokes. DOACs added £5953-£7018 per patient (UK), €6683-€7368 (Netherlands), €4933-€9378 (Spain), AUD$5353-6539 (Australia) and $26,768-$32,259 (US) of payer cost depending on the agent prescribed. Additionally, in the U.S. patient pharmacy co-payments ranged from $2468-$12,844 depending on agent and patient plan. In all settings, cost-savings could not be demonstrated even when the modelling assumed 100% protection from recurrent ischaemic strokes, due to the very low underlying risk of recurrent ischaemic stroke in this population (1.27 per 100 patient-years).

Conclusions: Anticoagulation of non-AF patients may cause excess bleeds and add substantial costs for uncertain benefits, suggesting a personalised approach to anticoagulation in ESUS patients.
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http://dx.doi.org/10.1186/s12872-021-01967-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015049PMC
March 2021

Delayed recurrent enhancing white matter lesions complicating coiling of intracranial aneurysm.

Eur J Neurol 2021 Mar 29. Epub 2021 Mar 29.

Second Department of Neurology, School of Medicine, "Attikon" University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Background And Purpose: In recent years, the use of coiling has gained increased popularity for the treatment of intracranial aneurysms, and stroke physicians are confronted with rare pathologies associated with this relatively new and evolving treatment method, such as embolization of pieces of the polymeric filaments from the coils and a subsequent inflammatory response. In particular, white matter enhancing lesions are a rare complication after aneurysm endovascular therapy (EVT), suggesting a foreign body reaction to shedding of hydrophilic coating from the endovascular devices into the blood stream. The description of such a case aims to raise the clinicians' awareness of the symptomatic delayed and recurring inflammatory changes that may occur after endovascular aneurysmal treatment with the use of coiling devices.

Case Description: A 64-year-old woman underwent coiling of a ruptured right posterior communicating artery aneurysm. She was asymptomatic after EVT. One year later, she presented with headache, acoustic hallucinations, paresthesias and left arm weakness. Brain magnetic resonance imaging (MRI) revealed multiple enhancing white matter lesions in the right hemisphere. She was treated with pulse intravenous methylprednisolone, followed by oral prednisolone; all clinical symptoms resolved and imaging findings improved substantially. Two years after tapering the steroids, follow-up symptoms recurred and repeat brain MRI revealed new enhancing white matter lesions.

Discussion And Conclusions: There is an increasing number of similar reports of enhancing white matter lesions after coiling of intracranial aneurysms, with the incidence estimated to be between 0.5% and 2.3% in different cohort studies. Close monitoring for the appearance of new neurologic symptoms that could suggest delayed brain reactivity should be recommended.
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http://dx.doi.org/10.1111/ene.14844DOI Listing
March 2021

Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic.

Stroke Vasc Neurol 2021 Mar 26. Epub 2021 Mar 26.

Department of Radiology, Beaumont Hospital, Dublin, Ireland.

Background: During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines.

Methods: We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation.

Findings: There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p<0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p<0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile.

Interpretation: There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.
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http://dx.doi.org/10.1136/svn-2020-000695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006491PMC
March 2021

Global Impact of COVID-19 on Stroke Care and Intravenous Thrombolysis.

Neurology 2021 Mar 25. Epub 2021 Mar 25.

Department of Neurology, University of North Carolina at Chapel Hill, North Carolina, USA.

Objective: The objectives of this study were to measure the global impact of the pandemic on the volumes for intravenous thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with two control 4-month periods.

Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases.

Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95%CI, -11.7 to - 11.3, p<0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95%CI, -13.8 to -12.7, p<0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95%CI, -13.7 to -10.3, p=0.001). Recovery of stroke hospitalization volume (9.5%, 95%CI 9.2-9.8, p<0.0001) was noted over the two later (May, June) versus the two earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.3% (1,722/52,026) of all stroke admissions.

Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.
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http://dx.doi.org/10.1212/WNL.0000000000011885DOI Listing
March 2021

Off-label use of intravenous thrombolysis for acute ischemic stroke: a critical appraisal of randomized and real-world evidence.

Ther Adv Neurol Disord 2021 26;14:1756286421997368. Epub 2021 Feb 26.

Department of Neurology, The University of Tennessee Health Science Center, Memphis, TN, USA.

Intravenous thrombolysis (IVT) represents the only systemic reperfusion therapy able to reverse neurological deficit in patients with acute ischemic stroke (AIS). Despite its effectiveness in patients with or without large vessel occlusion, it can be offered only to a minority of them, because of the short therapeutic window and additional contraindications derived from stringent but arbitrary inclusion and exclusion criteria used in landmark randomized controlled clinical trials. Many absolute or relative contraindications lead to disparities between the official drug label and guidelines or expert recommendations. Based on recent advances in neuroimaging and evidence from cohort studies, off-label use of IVT is increasingly incorporated into the daily practice of many stroke centers. They relate to extension of therapeutic time windows, and expansion of indications in co-existing conditions originally listed in exclusion criteria, such as use of alternative thrombolytic agents, pre-treatment with antiplatelets, anticoagulants or low molecular weight heparins. In this narrative review, we summarize recent randomized and real-world data on the safety and efficacy of off-label use of IVT for AIS. We also make some practical recommendations to stroke physicians regarding the off-label use of thrombolytic agents in complex and uncommon presentations of AIS or other conditions mimicking acute cerebral ischemia. Finally, we provide guidance on the risks and benefits of IVT in numerous AIS subgroups, where equipoise exists and guidelines and treatment practices vary.
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http://dx.doi.org/10.1177/1756286421997368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934037PMC
February 2021

Magnitude of blood pressure change and clinical outcomes after thrombectomy in stroke caused by large artery occlusion.

Eur J Neurol 2021 Mar 7. Epub 2021 Mar 7.

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Background: Extremes of both high and low systolic blood pressure (SBP) after mechanical thrombectomy (MT) in large artery occlusion stroke are known predictors of unfavorable outcome. However, the effect of SBP change (∆SBP) during the first 24 h on thrombectomy outcomes remains unclear. We aimed to investigate the association between ∆SBP at different time intervals and thrombectomy outcomes.

Methods: We analyzed MT-treated patients registered in the SITS International Stroke Thrombectomy Registry from January 1, 2014 to September 3, 2019. Primary outcome was 3-month unfavorable outcome (modified Rankin scale scores 3-6). We defined ∆SBP as the mean SBP of a given time interval after MT (0-2, 2-4, 4-12, 12-24 h) minus admission SBP. Multivariable mixed logistic regression models were used to adjust for known confounders and center as random effect. Subgroup analyses were included to contrast specific subpopulations. Restricted cubic splines were used to model the associations.

Results: The study population consisted of 5835 patients (mean age 70 years, 51% male, median NIHSS 16). Mean ∆SBP was -12.3, -15.7, -17.2, and -16.9 mmHg for the time intervals 0-2, 2-4, 4-12 h, and 12-24 h, respectively. Higher ∆SBP was associated with unfavorable outcome at 0-2 h (odds ratio 1.065, 95% confidence interval 1.014-1.118), 2-4 h (1.140, 1.081-1.203), 4-12 h (1.145, 1.087-1.203), and 12-24 h (1.145, 1.089-1.203), for every increase of 10 mmHg. Restricted cubic spline models suggested that increasing ∆SBP was associated with unfavorable outcome, with higher values showing increased risk of unfavorable outcome.

Conclusion: SBP increase after thrombectomy in large artery occlusion stroke is associated with poor functional outcome.
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http://dx.doi.org/10.1111/ene.14807DOI Listing
March 2021

Blood Biomarkers in Frontotemporal Dementia: Review and Meta-Analysis.

Brain Sci 2021 Feb 15;11(2). Epub 2021 Feb 15.

2nd Department of Neurology, School of Medicine, "Attikon" University General Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece.

Biomarkers in cerebrospinal fluid (CSF) are useful in the differential diagnosis between frontotemporal dementia (FTD) and Alzheimer's dementia (AD), but require lumbar puncture, which is a moderately invasive procedure that can cause anxiety to patients. Gradually, the measurement of blood biomarkers has been attracting great interest. Testing blood instead of CSF, in order to measure biomarkers, offers numerous advantages because it negates the need for lumbar puncture, it is widely available, and can be repeated, allowing the prediction of disease course. In this study, a systematic review of the existing literature was conducted, as well as meta-analysis with greater emphasis on the most studied biomarkers, p-tau and progranulin. The goal was to give prominence to evidence regarding the use of plasma biomarkers in clinical practice.
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http://dx.doi.org/10.3390/brainsci11020244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919273PMC
February 2021

A nomogram to predict unfavourable outcome in patients receiving oral anticoagulants for atrial fibrillation after stroke.

Eur Stroke J 2020 Dec 26;5(4):384-393. Epub 2020 Nov 26.

Neurology and Stroke Center, University Hospital Basel and University of Basel, Basel, Switzerland.

Introduction: It is unknown whether the type of treatment (direct oral anticoagulant versus vitamin K antagonist) and the time of treatment introduction (early versus late) may affect the functional outcome in stroke patients with atrial fibrillation. We aimed to develop and validate a nomogram model including direct oral anticoagulant/vitamin K antagonist and early/late oral anticoagulant introduction for predicting the probability of unfavourable outcome after stroke in atrial fibrillation-patients.

Patients And Methods: We conducted an individual patient data analysis of four prospective studies. Unfavourable functional outcome was defined as three-month modified Rankin Scale score 3 -6. To generate the nomogram, five independent predictors including age (<65 years, reference; 65--79; or 80), National Institutes of Health Stroke Scale score (0--5 points, reference; 6--15; 16--25; or >25), acute revascularisation treatments (yes, reference, or no), direct oral anticoagulant (reference) or vitamin K antagonist, and early (7 days, reference) or late (8--30) anticoagulant introduction entered into a final logistic regression model. The discriminative performance of the model was assessed by using the area under the receiver operating characteristic curve.

Results: A total of 2102 patients with complete data for generating the nomogram was randomly dichotomised into training ( = 1553) and test ( = 549) sets. The area under the receiver operating characteristic curve was 0.822 (95% confidence interval, CI: 0.800--0.844) in the training set and 0.803 (95% CI: 0.764--0.842) in the test set. The model was adequately calibrated (9.852;  = 0.276 for the Hosmer--Lemeshow test).

Discussion And Conclusion: Our nomogram is the first model including type of oral anticoagulant and time of treatment introduction to predict the probability of three-month unfavourable outcome in a large multicentre cohort of stroke patients with atrial fibrillation.
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http://dx.doi.org/10.1177/2396987320945840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856583PMC
December 2020

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes.

Eur Stroke J 2020 Dec 22;5(4):374-383. Epub 2020 Jul 22.

Internal Medicine, San Giuseppe Hospital, Empoli, Italy.

Introduction: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing.

Materials And Methods: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke.

Results: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80).

Discussion: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events.

Conclusions: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.
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http://dx.doi.org/10.1177/2396987320937116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856592PMC
December 2020

Cerebral microbleeds: from depiction to interpretation.

J Neurol Neurosurg Psychiatry 2021 Feb 9. Epub 2021 Feb 9.

Department of Neurology, U1172 - LilNCog - Lille Neuroscience & Cognition, Univ. Lille, Inserm, CHU Lille, F-59000 Lille, France

Cerebral microbleeds (CMBs) are defined as hypointense foci visible on T2*-weighted and susceptible-weighted MRI sequences. CMBs are increasingly recognised with the widespread use of MRI in healthy individuals as well as in the context of cerebrovascular disease or dementia. They can also be encountered in major critical medical conditions such as in patients requiring extracorporeal mechanical oxygenation. The advent of MRI-guided postmortem neuropathological examinations confirmed that, in the context of cerebrovascular disease, the vast majority of CMBs correspond to recent or old microhaemorrhages. Detection of CMBs is highly influenced by MRI parameters, in particular field strength, postprocessing methods used to enhance T2* contrast and three dimensional sequences. Despite recent progress, harmonising imaging parameters across research studies remains necessary to improve cross-study comparisons. CMBs are helpful markers to identify the nature and the severity of the underlying chronic small vessel disease. In daily clinical practice, presence and numbers of CMBs often trigger uncertainty for clinicians especially when antithrombotic treatments and acute reperfusion therapies are discussed. In the present review, we discuss those clinical dilemmas and address the value of CMBs as diagnostic and prognostic markers for future vascular events.
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http://dx.doi.org/10.1136/jnnp-2020-323951DOI Listing
February 2021

Perfusion imaging averting intravenous thrombolysis in stroke mimics.

Neurol Sci 2021 Feb 5. Epub 2021 Feb 5.

Second Department of Neurology, National and Kapodistrian University of Athens, School of Medicine, "Attikon" University Hospital, Athens, Greece.

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http://dx.doi.org/10.1007/s10072-021-05090-9DOI Listing
February 2021

Off-label intravenous thrombolysis for early recurrent brain embolism associated with aortic arch thrombus.

Neurol Res Pract 2021 Jan 16;3(1). Epub 2021 Jan 16.

Second Department of Neurology, Aristotle University of Thessaloniki, School of Medicine, Faculty of Health Sciences, AHEPA University Hospital, Thessaloniki, Greece.

Safety data of intravenous thrombolysis (IVT) in presence of aortic arch thrombus is scant. Furthermore, IVT is debatable in patients with prior recent stroke. We present a 51-year-old woman with recurrent major infarction 5 days after a minor left MCA territory stroke. She had a floating aortic arch thrombus and she was treated safely and effectively with off-label IVT. Patients with small infarct volumes and mild/no residual neurological deficits after an initial stroke might be considered for IVT in case of early recurrence. IVT may be reasonable in a context of acute severely disabling stroke associated with aortic arch thrombus.
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http://dx.doi.org/10.1186/s42466-021-00103-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811222PMC
January 2021

Real-world comparative safety and efficacy of tenecteplase alteplase in acute ischemic stroke patients with large vessel occlusion.

Ther Adv Neurol Disord 2021 12;14:1756286420986727. Epub 2021 Jan 12.

Second Department of Neurology, Attikon University Hospital, School of Medicine, University of Athens, Athens, Greece.

Background And Aims: Tenecteplase has recently emerged as an alternative thrombolytic agent in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO), possibly superior in achieving early reperfusion compared with alteplase. We aimed to compare the safety and efficacy of intravenous tenecteplase with intravenous alteplase for AIS patients with LVO in everyday clinical practice settings.

Methods: We prospectively evaluated patients with AIS due to LVO, treated with intravenous thrombolysis (IVT) with or without mechanical thrombectomy in two tertiary stroke centers. Patients were treated with standard-dose alteplase (0.9 mg/kg) or 0.25 mg/kg tenecteplase. Safety outcomes included prevalence of symptomatic intracranial hemorrhage (sICH) and mortality. Efficacy outcomes included averted thrombectomy, major neurological improvement at 24 h (defined as decrease in baseline NIHSS score of 8 points or greater) and functional status on discharge and on 3 months assessed by modified Rankin Scale (mRS).

Results: Nineteen AIS patients with LVO received tenecteplase and 39 received alteplase. We observed a non-significant higher rate of averted thrombectomies (32% 18%,  = 0.243) and a non-significant higher rate of sICH (16% 5%,  = 0.201) in the tenecteplase group. The rate of 24 h major neurological improvement was higher in the tenecteplase group (64% 33%,  = 0.046) but this was marginally attenuated in multivariable analyses (adjusted OR 10.22, 95% CI: 0.73-142.98;  = 0.084). Discharge mRS, 3-months mRS, and 3-month functional independence (mRS scores of 0-2) did not differ ( > 0.2) between the two groups. The rates of 3-month mortality (11% 18%,  = 0.703) were similar in the two groups. No independent association between thrombolytic agent and safety or efficacy outcomes emerged in multivariable regression analyses.

Conclusion: The present pilot observational study highlights that AIS patients with LVO treated with 0.25 mg/kg bolus administration of tenecteplase had increased likelihood to achieve early neurological improvement compared with AIS patients treated with alteplase, but this association was attenuated after adjustment for potential confounders. There were no significant differences in 3-month functional or safety outcomes between the two groups. This preliminary real-world observation requires independent confirmation in larger, multicenter studies.
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http://dx.doi.org/10.1177/1756286420986727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809628PMC
January 2021

Endovascular treatment for basilar artery occlusion: A systematic review and meta-analysis.

Eur J Neurol 2021 Jan 22. Epub 2021 Jan 22.

Second Department of Neurology, School of Medicine, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Background And Purpose: Independent randomized controlled clinical trials (RCTs) have provided robust evidence for endovascular treatment (EVT) as the standard of care treatment for acute large vessel occlusions in the anterior circulation. We examined available studies specific to posterior cerebral circulation ischemic strokes to see if any conclusions can be drawn regarding EVT options.

Methods: We performed a systematic literature search to identify studies evaluating the safety and efficacy of EVT versus standard medical treatment for patients with acute basilar artery occlusion (BAO). We extracted data for outcomes of interest and presented associations between the two groups with the use of risk ratios (RRs) or odds ratios (ORs), with corresponding 95% confidence intervals (CIs). We used a random-effects model to pool the effect estimates.

Results: We identified five studies (two RCTs, three observational cohorts) including a total of 1098 patients. Patients receiving EVT had a higher risk of symptomatic intracranial hemorrhage (sICH) compared to those receiving non-interventional medical management (RR 5.42, 95% CI 2.74-10.71). Nonsignificant trends towards modified Rankin Scale (mRS) scores 0-2 (RR 1.02, 95% CI 0.74-1.41), mRS scores 0-3 (RR = 0.97, 95% CI 0.64-1.47), overall functional improvement (OR 0.93, 95% CI 0.57-1.51), and all-cause mortality (RR 1.03, 95% CI 0.78-1.35) at 3 months were seen.

Conclusion: Although EVT increases the probability of sICH, the available data do not exclude the possibility of improved functional outcomes over standard therapy. As larger studies are challenged by the perceived lack of equipoise in this vulnerable patient population, results of ongoing RCTs are expected to provide substantial input for future meta-analyses.
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http://dx.doi.org/10.1111/ene.14751DOI Listing
January 2021

Global impact of COVID-19 on stroke care.

Int J Stroke 2021 Mar 29:1747493021991652. Epub 2021 Mar 29.

Neurology, Grady Memorial Hospital, Emory University, Atlanta, Georgia, USA.

Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide.

Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March-31 May 2020) compared with two control three-month periods (immediately preceding and one year prior).

Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers.

Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, -19.7 to -18.7), 11.5% (95%CI, -12.6 to -10.6), and 12.7% (95%CI, -13.6 to -11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (-20.5%) had greater declines in mechanical thrombectomy volumes than mid- (-10.1%) and low-volume (-8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions.

Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes.
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http://dx.doi.org/10.1177/1747493021991652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010375PMC
March 2021

Prevalence of patent foramen ovale in the Greek population is high and impacts on the interpretation of the risk of paradoxical embolism (RoPE) score.

Ther Adv Neurol Disord 2020 10;13:1756286420964673. Epub 2020 Oct 10.

2nd Department of Neurology, Aristotle University of Thessaloniki, AHEPA University Hospital, S.Kyriakidi 1, Thessaloniki, 54636, Greece.

Background: The risk of paradoxical embolism (RoPE) score calculates the probability that patent foramen ovale (PFO) is causally related to stroke (PFO attributable fraction, PFOAF), based on PFO prevalence in patients with cryptogenic stroke (CS) compared with that in the general population. The latter has been estimated at 25%; however, PFO prevalence in nonselected populations varies widely.

Methods: Since PFO prevalence in Greece remains unknown, we evaluated it and we calculated PFOAF stratified by RoPE score in a cohort of patients with CS ⩽55 years old. PFO was detected according to the international consensus transcranial Doppler (TCD) criteria in 124 healthy subjects (H), in 102 patients with CS, and in 56 patients with stroke of known cause (nonCS). Each subject underwent unilateral middle cerebral artery recording after infusion of agitated saline, at rest, and after a controlled Valsalva maneuver. We characterized PFO as large (>20 microbubbles or curtain), moderate (11-20), and small (⩽10).

Results: PFO was detected in 42.7% of H, 49% of CS, and 25% of nonCS ( = 0.013). Large PFOs were numerically higher in CS [28.4% (29/102)] compared with H [19.3% (24/124);  = 0.1] and to nonCS [7.1% (4/56),  = 0.04]. The median RoPE score in patients with CS and PFO was seven. Even patients with very high RoPE score (9-10) had moderate PFOAF (57%). For any individual stratum up to RopE score 8, PFOAF was <33%.

Conclusions: PFO prevalence in the Greek population is much higher than the widely accepted 25%. PFO may be the cause of stroke in one out of nine Greek patients with CS. Among Greek CS patients who harbor a PFO, the latter is causal in one out of five. The established RoPE score cutoff of ⩾7 for having a probable PFO-associated stroke may overestimate the probability in patients deriving from populations with high PFO prevalence.
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http://dx.doi.org/10.1177/1756286420964673DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758802PMC
October 2020

COVID-19: Neuroimaging Features of a Pandemic.

J Neuroimaging 2021 03 9;31(2):228-243. Epub 2021 Jan 9.

Department of Neurology, St. Josef-Hospital Bochum, Ruhr University Bochum, Bochum, Germany.

Background And Purpose: The ongoing Coronavirus Disease 2019 (COVID-19) pandemic is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is occasionally associated with manifold diseases of the central nervous system (CNS). We sought to present the neuroimaging features of such CNS involvement. In addition, we sought to identify typical neuroimaging patterns that could indicate possible COVID-19-associated neurological manifestations.

Methods: In this systematic literature review, typical neuroimaging features of cerebrovascular diseases and inflammatory processes associated with COVID-19 were analyzed. Reports presenting individual patient data were included in further quantitative analysis with descriptive statistics.

Results: We identified 115 studies reporting a total of 954 COVID-19 patients with associated neurological manifestations and neuroimaging alterations. A total of 95 (82.6%) of the identified studies were single case reports or case series, whereas 660 (69.2%) of the reported cases included individual information and were thus included in descriptive statistical analysis. Ischemia with neuroimaging patterns of large vessel occlusion event was revealed in 59.9% of ischemic stroke patients, whereas 69.2% of patients with intracerebral hemorrhage exhibited bleeding in a location that was not associated with hypertension. Callosal and/or juxtacortical location was identified in 58.7% of cerebral microbleed positive images. Features of hemorrhagic necrotizing encephalitis were detected in 28.8% of patients with meningo-/encephalitis.

Conclusions: Manifold CNS involvement is increasingly reported in COVID-19 patients. Typical and atypical neuroimaging features have been observed in some disease entities, so that familiarity with these imaging patterns appears reasonable and may assist clinicians in the differential diagnosis of COVID-19 CNS manifestations.
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http://dx.doi.org/10.1111/jon.12819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014046PMC
March 2021