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1.
Neuroradiology ; 64(7): 1367-1372, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1626879

ABSTRACT

PURPOSE: Intracerebral hemorrhage (ICH) is an uncommon but deadly event in patients with COVID-19 and its imaging features remain poorly characterized. We aimed to describe the clinical and imaging features of COVID-19-associated ICH. METHODS: Multicenter, retrospective, case-control analysis comparing ICH in COVID-19 patients (COV19 +) versus controls without COVID-19 (COV19 -). Clinical presentation, laboratory markers, and severity of COVID-19 disease were recorded. Non-contrast computed tomography (NCCT) markers (intrahematoma hypodensity, heterogeneous density, blend sign, irregular shape fluid level), ICH location, and hematoma volume (ABC/2 method) were analyzed. The outcome of interest was ultraearly hematoma growth (uHG) (defined as NCCT baseline ICH volume/onset-to-imaging time), whose predictors were explored with multivariable linear regression. RESULTS: A total of 33 COV19 + patients and 321 COV19 - controls with ICH were included. Demographic characteristics and vascular risk factors were similar in the two groups. Multifocal ICH and NCCT markers were significantly more common in the COV19 + population. uHG was significantly higher among COV19 + patients (median 6.2 mL/h vs 3.1 mL/h, p = 0.027), and this finding remained significant after adjustment for confounding factors (systolic blood pressure, antiplatelet and anticoagulant therapy), in linear regression (B(SE) = 0.31 (0.11), p = 0.005). This association remained consistent also after the exclusion of patients under anticoagulant treatment (B(SE) = 0.29 (0.13), p = 0.026). CONCLUSIONS: ICH in COV19 + patients has distinct NCCT imaging features and a higher speed of bleeding. This association is not mediated by antithrombotic therapy and deserves further research to characterize the underlying biological mechanisms.


Subject(s)
COVID-19 , Anticoagulants , Biomarkers , COVID-19/complications , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/diagnostic imaging , Hematoma/diagnostic imaging , Humans , Retrospective Studies
2.
Clin Infect Dis ; 73(9): e3019-e3026, 2021 11 02.
Article in English | MEDLINE | ID: covidwho-1501050

ABSTRACT

BACKGROUND: Recent findings indicated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related neurological manifestations involve cytokine release syndrome along with endothelial activation, blood brain barrier dysfunction, and immune-mediated mechanisms. Very few studies have fully investigated the cerebrospinal fluid (CSF) correlates of SARS-CoV-2 encephalitis. METHODS: Patients with polymerase chain reaction (PCR)-confirmed SARS-CoV-2 infection and encephalitis (COV-Enc), encephalitis without SARS-CoV-2 infection (ENC), and healthy controls (HC) underwent an extended panel of CSF neuronal (neurofilament light chain [NfL], T-tau), glial (glial fibrillary acidic protein [GFAP], soluble triggering receptor expressed on myeloid cells 2 [sTREM2], chitinase-3-like protein 1 [YKL-40]) and inflammatory biomarkers (interleukin [IL]-1ß, IL-6, Il-8, tumor necrosis factor [TNF] α, CXCL-13, and ß2-microglobulin). RESULTS: Thirteen COV-Enc, 21 ENC, and 18 HC entered the study. In COV-Enc cases, CSF was negative for SARS-CoV-2 real-time PCR but exhibited increased IL-8 levels independently from presence of pleocytosis/hyperproteinorracchia. COV-Enc patients showed increased IL-6, TNF- α, and ß2-microglobulin and glial markers (GFAP, sTREM2, YKL-40) levels similar to ENC but normal CXCL13 levels. Neuronal markers NfL and T-tau were abnormal only in severe cases. CONCLUSIONS: SARS-CoV-2-related encephalitis were associated with prominent glial activation and neuroinflammatory markers, whereas neuronal markers were increased in severe cases only. The pattern of CSF alterations suggested a cytokine-release syndrome as the main inflammatory mechanism of SARS-CoV-2-related encephalitis.


Subject(s)
COVID-19 , Encephalitis , Cytokine Release Syndrome , Glial Fibrillary Acidic Protein , Humans , SARS-CoV-2
3.
Acta Neurochir (Wien) ; 164(1): 141-150, 2022 01.
Article in English | MEDLINE | ID: covidwho-1482221

ABSTRACT

BACKGROUND: Lombardy was the most affected Italian region by the first phase of the COVID-19 pandemic and underwent urgent reorganization for the management of emergencies, including subarachnoid hemorrhage from a ruptured cerebral aneurysm (aSAH). The aim of the study was to define demographics, clinical, and therapeutic features of aSAH during the COVID-19 outbreak and compare these with a historical cohort. METHODS: In this observational multicenter cohort study, patients aged 18 years or older, who were diagnosed with aSAH at the participating centers in Lombardy from March 9 to May 10, 2020, were included (COVID-19 group). In order to minimize bias related to possible SAH seasonality, the control group was composed of patients diagnosed with aSAH from March 9 to May 10 of the three previous years, 2017-2018-2019 (pre-pandemic group). Twenty-three demographic, clinical, and therapeutic features were collected. Statistical analysis was performed. RESULTS: Seventy-two patients during the COVID-19 period and 179 in the control group were enrolled at 14 centers. Only 4 patients were positive for SARS-CoV-2. The "diagnostic delay" was significantly increased (+ 68%) in the COVID-19 group vs. pre-pandemic (1.06 vs. 0.63 days, respectively, p-value = 0.030), while "therapeutic delay" did not differ significantly between the two periods (0.89 vs. 0.74 days, p-value = 0.183). Patients with poor outcome (GOS at discharge from 1 to 3) were higher during the COVID-19 period (54.2%) compared to pre-pandemic (40.2%, p = 0.044). In logistic regression analysis, in which outcome was the dichotomized Glasgow Outcome Scale (GOS), five variables showed p-values < 0.05: age at admission, WFNS grade, treatment (none), days in ICU, and ischemia. CONCLUSIONS: We documented a significantly increased "diagnostic delay" for subarachnoid hemorrhages during the first COVID-19 outbreak in Lombardy. However, despite the dramatic situation that the healthcare system was experiencing, the Lombardy regional reorganization model, which allowed centralization of neurosurgical emergencies such as SAHs, avoided a "therapeutic delay" and led to results overall comparable to the control period.


Subject(s)
COVID-19 , Subarachnoid Hemorrhage , Cohort Studies , Humans , Pandemics , SARS-CoV-2 , Subarachnoid Hemorrhage/epidemiology , Treatment Outcome
5.
Neurobiol Stress ; 14: 100326, 2021 May.
Article in English | MEDLINE | ID: covidwho-1180112

ABSTRACT

COVID-19, the infectious disease caused by the most recently discovered severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has become a global pandemic. It dramatically affects people's health and daily life. Neurological complications are increasingly documented for patients with COVID-19. However, the effect of COVID-19 on the brain is less studied, and existing quantitative neuroimaging analyses of COVID-19 were mainly based on the univariate voxel-based morphometry analysis (VBM) that requires corrections for a large number of tests for statistical significance, multivariate approaches that can reduce the number of tests to be corrected have not been applied to study COVID-19 effect on the brain yet. In this study, we leveraged source-based morphometry (SBM) analysis, a multivariate extension of VBM, to identify changes derived from computed tomography scans in covarying gray matter volume patterns underlying COVID-19 in 120 neurological patients (including 58 cases with COVID-19 and 62 patients without COVID-19 matched for age, gender and diseases). SBM identified that lower gray matter volume (GMV) in superior/medial/middle frontal gyri was significantly associated with a higher level of disability (modified Rankin Scale) at both discharge and six months follow-up phases even when controlling for cerebrovascular diseases. GMV in superior/medial/middle frontal gyri was also significantly reduced in patients receiving oxygen therapy compared to patients not receiving oxygen therapy. Patients with fever presented significant GMV reduction in inferior/middle temporal gyri and fusiform gyrus compared to patients without fever. Patients with agitation showed GMV reduction in superior/medial/middle frontal gyri compared to patients without agitation. Patients with COVID-19 showed no significant GMV differences from patients without COVID-19 in any brain region. Results suggest that COVID-19 may affect the frontal-temporal network in a secondary manner through fever or lack of oxygen.

6.
J Infect Dis ; 223(1): 28-37, 2021 01 04.
Article in English | MEDLINE | ID: covidwho-1066338

ABSTRACT

BACKGROUND: Several preclinical and clinical investigations have argued for nervous system involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Some sparse case reports have described various forms of encephalitis in coronavirus disease 2019 (COVID-19) disease, but very few data have focused on clinical presentations, clinical course, response to treatment, and outcomes. METHODS: The SARS-CoV-2 related encephalopaties (ENCOVID) multicenter study included patients with encephalitis with full infectious screening, cerebrospinal fluid (CSF), electroencephalography (EEG), and magnetic resonance imaging (MRI) data and confirmed SARS-CoV-2 infection recruited from 13 centers in northern Italy. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment, and outcomes were recorded. RESULTS: Twenty-five cases of encephalitis positive for SARS-CoV-2 infection were included. CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by reverse-transcription polymerase chain reaction resulted negative. Based on MRI, cases were classified as acute demyelinating encephalomyelitis (ADEM; n = 3), limbic encephalitis (LE; n = 2), encephalitis with normal imaging (n = 13), and encephalitis with MRI alterations (n = 7). ADEM and LE cases showed a delayed onset compared to the other encephalitis cases (P = .001) and were associated with previous, more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to those with other encephalitis. CONCLUSIONS: SARS-CoV-2 infection is associated with a wide spectrum of encephalitis characterized by different clinical presentation, response to treatment, and outcomes.


Subject(s)
COVID-19/complications , Encephalitis/diagnosis , Aged , Aged, 80 and over , COVID-19/therapy , Electroencephalography , Encephalitis/classification , Encephalitis/virology , Female , Humans , Italy , Longitudinal Studies , Magnetic Resonance Imaging , Male , Middle Aged
7.
Stroke ; 52(1): 31-39, 2021 01.
Article in English | MEDLINE | ID: covidwho-939945

ABSTRACT

BACKGROUND AND PURPOSE: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. METHODS: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. SECONDARY OUTCOMES: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0-1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. RESULTS: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59-79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11-21) and 8 (interquartile range, 7-9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3-87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20-39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8-29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7-12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21-5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22-5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43-12.91] per SD-log increase in LDH). CONCLUSIONS: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient's profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04406090.


Subject(s)
COVID-19/complications , Endovascular Procedures , Ischemic Stroke/complications , Ischemic Stroke/surgery , Thrombectomy , Aged , Aged, 80 and over , COVID-19/epidemiology , Cohort Studies , Endovascular Procedures/mortality , Europe , Female , Humans , Ischemic Stroke/mortality , Male , Middle Aged , Registries , Risk Factors , SARS-CoV-2 , Thrombectomy/mortality , Treatment Outcome
9.
J Neurol Neurosurg Psychiatry ; 92(2): 218-220, 2021 02.
Article in English | MEDLINE | ID: covidwho-873577
10.
Ann Neurol ; 88(2): 423-427, 2020 08.
Article in English | MEDLINE | ID: covidwho-600958

ABSTRACT

Coronavirus disease 2019 (COVID-19) infection has the potential for targeting the central nervous system, and several neurological symptoms have been described in patients with severe respiratory distress. Here, we described the case of a 60-year-old patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection but only mild respiratory abnormalities who developed an akinetic mutism attributable to encephalitis. Magnetic resonance imaging was negative, whereas electroencephalography showed generalized theta slowing. Cerebrospinal fluid analyses during the acute stage were negative for SARS-CoV-2, positive for pleocytosis and hyperproteinorrachia, and showed increased interleukin-8 and tumor necrosis factor-α concentrations. Other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of cerebrospinal fluid parameters was observed after high-dose steroid treatment, thus arguing for an inflammatory-mediated brain involvement related to COVID-19. ANN NEUROL 2020;88:423-427.


Subject(s)
Akinetic Mutism/physiopathology , Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Encephalitis/drug therapy , Glucocorticoids/therapeutic use , Methylprednisolone/therapeutic use , Pneumonia, Viral/drug therapy , Betacoronavirus , COVID-19 , Coronavirus Infections/cerebrospinal fluid , Coronavirus Infections/complications , Coronavirus Infections/physiopathology , Drug Combinations , Electroencephalography , Encephalitis/cerebrospinal fluid , Encephalitis/complications , Encephalitis/physiopathology , Humans , Hydroxychloroquine/therapeutic use , Interleukin-6/cerebrospinal fluid , Interleukin-8/cerebrospinal fluid , Lopinavir/therapeutic use , Magnetic Resonance Imaging , Male , Middle Aged , Pandemics , Pneumonia, Viral/cerebrospinal fluid , Pneumonia, Viral/complications , Pneumonia, Viral/physiopathology , Ritonavir/therapeutic use , SARS-CoV-2 , Treatment Outcome , Tumor Necrosis Factor-alpha/cerebrospinal fluid , beta 2-Microglobulin/cerebrospinal fluid
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