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1.
Neurol Clin Pract ; 11(2): e64-e72, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1304433

ABSTRACT

BACKGROUND: An increasing number of neurologic problems are being described in coronavirus disease 2019 (COVID-19) disease, but their frequency and type have not been defined. In this study, we sought to determine the extent of neurologic manifestations of COVID-19 in a prospective series of unselected patients admitted to the general medicine wards of our hospitals due to COVID-19 and who were examined by a team of neurologists. METHODS: Eight neurologists provided medical attention to patients hospitalized for COVID-19 to provide medical support to other hospital units tasked with the care of an increasingly larger influx of patients with COVID-19. A series of 100 consecutive, unselected patients were evaluated systematically, including a questionnaire that collected medical information derived from the initial examination and the medical history. RESULTS: Eighty-eight percent of the patients had 1 neurologic manifestation associated with COVID-19 during hospitalization. Most common were anosmia-dysgeusia and headache (44% each), myalgias (43%), and dizziness (36%). Less frequent were encephalopathy (8%), syncope (7%), seizures (2%), and ischemic stroke during the period of hospitalization (2%). Anosmia and headache associated with younger patients with less severe disease, and both were associated with each other and with serum inflammatory markers. Encephalopathy was associated with fever and syncope and with markers of inflammation. CONCLUSIONS: Neurologic disturbances are common in patients with COVID-19, particularly if patients are evaluated by neurologists. There is a wide variety of neurologic conditions, some of them severe, in the spectrum of COVID-19 disease that will benefit from an evaluation by practicing neurologists.

2.
CNS Neurosci Ther ; 27(10): 1127-1135, 2021 10.
Article in English | MEDLINE | ID: covidwho-1270830

ABSTRACT

AIMS: To determine if neurologic symptoms at admission can predict adverse outcomes in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: Electronic medical records of 1053 consecutively hospitalized patients with laboratory-confirmed infection of SARS-CoV-2 from one large medical center in the USA were retrospectively analyzed. Univariable and multivariable Cox regression analyses were performed with the calculation of areas under the curve (AUC) and concordance index (C-index). Patients were stratified into subgroups based on the presence of encephalopathy and its severity using survival statistics. In sensitivity analyses, patients with mild/moderate and severe encephalopathy (defined as coma) were separately considered. RESULTS: Of 1053 patients (mean age 52.4 years, 48.0% men [n = 505]), 35.1% (n = 370) had neurologic manifestations at admission, including 10.3% (n = 108) with encephalopathy. Encephalopathy was an independent predictor for death (hazard ratio [HR] 2.617, 95% confidence interval [CI] 1.481-4.625) in multivariable Cox regression. The addition of encephalopathy to multivariable models comprising other predictors for adverse outcomes increased AUCs (mortality: 0.84-0.86, ventilation/ intensive care unit [ICU]: 0.76-0.78) and C-index (mortality: 0.78 to 0.81, ventilation/ICU: 0.85-0.86). In sensitivity analyses, risk stratification survival curves for mortality and ventilation/ICU based on severe encephalopathy (n = 15) versus mild/moderate encephalopathy (n = 93) versus no encephalopathy (n = 945) at admission were discriminative (p < 0.001). CONCLUSIONS: Encephalopathy at admission predicts later progression to death in SARS-CoV-2 infection, which may have important implications for risk stratification in clinical practice.


Subject(s)
Brain Diseases/diagnosis , Brain Diseases/mortality , COVID-19/diagnosis , COVID-19/mortality , Patient Admission/trends , Adult , Aged , Brain Diseases/therapy , COVID-19/therapy , Cohort Studies , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies
3.
Crit Care Explor ; 3(6): e0456, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1270759

ABSTRACT

To determine if early CNS symptoms are associated with severe coronavirus disease 2019. DESIGN: A retrospective, observational case series study design. SETTING: Electronic health records were reviewed for patients from five healthcare systems across the state of Florida, United States. PATIENTS: A clinical sample (n = 36,615) of patients with confirmed diagnosis of coronavirus disease 2019 were included. Twelve percent (n = 4,417) of the sample developed severe coronavirus disease 2019, defined as requiring critical care, mechanical ventilation, or diagnosis of acute respiratory distress syndrome, sepsis, or severe inflammatory response syndrome. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: We reviewed the electronic health record for diagnosis of early CNS symptoms (encephalopathy, headache, ageusia, anosmia, dizziness, acute cerebrovascular disease) between 14 days before the diagnosis of coronavirus disease 2019 and 8 days after the diagnosis of coronavirus disease 2019, or before the date of severe coronavirus disease 2019 diagnosis, whichever came first. Hierarchal logistic regression models were used to examine the odds of developing severe coronavirus disease 2019 based on diagnosis of early CNS symptoms. Severe coronavirus disease 2019 patients were significantly more likely to have early CNS symptoms (32.8%) compared with nonsevere patients (6.11%; χ2[1] = 3,266.08, p < 0.0001, φ = 0.29). After adjusting for demographic variables and pertinent comorbidities, early CNS symptoms were significantly associated with severe coronavirus disease 2019 (odds ratio = 3.21). Diagnosis of encephalopathy (odds ratio = 14.38) was associated with greater odds of severe coronavirus disease 2019; whereas diagnosis of anosmia (odds ratio = 0.45), ageusia (odds ratio = 0.46), and headache (odds ratio = 0.63) were associated with reduced odds of severe coronavirus disease 2019. CONCLUSIONS: Early CNS symptoms, and specifically encephalopathy, are differentially associated with risk of severe coronavirus disease 2019 and may serve as an early marker for differences in clinical disease course. Therapies for early coronavirus disease 2019 are scarce, and further identification of subgroups at risk may help to advance understanding of the severity trajectories and enable focused treatment.

4.
J Neurol Res ; 10(5): 164-172, 2020 Oct.
Article in English | MEDLINE | ID: covidwho-1227227

ABSTRACT

Coronavirus disease 2019 (COVID-19) disease caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been associated with many neurological symptoms. The purpose of this article is to describe the neurological manifestations so far reported and their probable pathogenesis. We conducted a literature review on EMBASE, MEDLINE and SCIELO databases using the terms "COVID-19", "COVID", "neurological", "neurologic", "manifestations", "implications", "Guillain-Barre syndrome", "encephalopathy". A total of 33 articles including clinical series, retrospective studies, and case reports were selected and thoroughly reviewed to describe neurological manifestations of COVID-19. There are several neurological manifestations of SARS-CoV-2 infection with different clinical presentations, severity, and prevalence. The most critical ones, such as cerebrovascular disease, encephalopathy, and Guillain-Barre syndrome, were less common and usually associated with previous medical history, known risk factors for cerebrovascular disease or advanced age. The main hypotheses for the spread of the virus are through the hematogenous route or the cribriform plate of the ethmoid bone or a disseminated severe immune response by a cytokine storm. The presence of neurological disturbances associated with laboratory tests alterations is an important clue for the physicians to promptly recognize neurological manifestations of SARS-CoV-2.

5.
BMJ Case Rep ; 14(5)2021 May 10.
Article in English | MEDLINE | ID: covidwho-1223565

ABSTRACT

Teprotumumab (Tepezza), an insulin-like growth factor type 1 receptor antagonist, was approved for treatment of thyroid eye disease in 2020. Teprotumumab is administered intravenously every 3 weeks for a total of eight doses. Common side effects include nausea, diarrhoea, muscle spasms, hearing impairment, dysgeusia, headaches, dry skin, infusion reactions and hyperglycaemia. We report here a 76-year-old man with Graves-related thyroid eye disease who developed a rapidly progressive cognitive decline after receiving four out of eight doses of teprotumumab (cumulative dose 4620 mg). He was admitted for workup and teprotumumab infusions were discontinued. Intravenous glucocorticoids and immunoglobulin were given which showed no improvement in clinical symptoms. He subsequently underwent plasmapheresis with resolution of his symptoms, suggesting a teprotumumab-induced encephalopathy. Further studies involving larger populations and longer durations are needed.


Subject(s)
Cognitive Dysfunction , Graves Ophthalmopathy , Aged , Antibodies, Monoclonal, Humanized , Graves Ophthalmopathy/drug therapy , Humans , Male
6.
Ann Neurol ; 89(5): 1041-1045, 2021 05.
Article in English | MEDLINE | ID: covidwho-1100843

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) can present with distinct neurological manifestations. This study shows that inflammatory neurological diseases were associated with increased levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IL-12, chemokine (C-X-C motif) ligand 8 (CXCL8), and CXCL10 in the cerebrospinal fluid. Conversely, encephalopathy was associated with high serum levels of IL-6, CXCL8, and active tumor growth factor ß1. Inflammatory syndromes of the central nervous system in COVID-19 can appear early, as a parainfectious process without significant systemic involvement, or without direct evidence of severe acute respiratory syndrome coronavirus 2 neuroinvasion. At the same time, encephalopathy is mainly influenced by peripheral events, including inflammatory cytokines. ANN NEUROL 2021;89:1041-1045.


Subject(s)
COVID-19/blood , COVID-19/cerebrospinal fluid , Inflammation Mediators/blood , Inflammation Mediators/cerebrospinal fluid , Nervous System Diseases/blood , Nervous System Diseases/cerebrospinal fluid , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/epidemiology , Cytokines/blood , Cytokines/cerebrospinal fluid , Humans , Nervous System Diseases/epidemiology
7.
Clin Microbiol Infect ; 27(3): 458-466, 2021 Mar.
Article in English | MEDLINE | ID: covidwho-973978

ABSTRACT

OBJECTIVES: To provide an overview of the spectrum, characteristics and outcomes of neurologic manifestations associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: We conducted a single-centre retrospective study during the French coronavirus disease 2019 (COVID-19) epidemic in March-April 2020. All COVID-19 patients with de novo neurologic manifestations were eligible. RESULTS: We included 222 COVID-19 patients with neurologic manifestations from 46 centres in France. Median (interquartile range, IQR) age was 65 (53-72) years and 136 patients (61.3%) were male. COVID-19 was severe or critical in 102 patients (45.2%). The most common neurologic diseases were COVID-19-associated encephalopathy (67/222, 30.2%), acute ischaemic cerebrovascular syndrome (57/222, 25.7%), encephalitis (21/222, 9.5%) and Guillain-Barré syndrome (15/222, 6.8%). Neurologic manifestations appeared after the first COVID-19 symptoms with a median (IQR) delay of 6 (3-8) days in COVID-19-associated encephalopathy, 7 (5-10) days in encephalitis, 12 (7-18) days in acute ischaemic cerebrovascular syndrome and 18 (15-28) days in Guillain-Barré syndrome. Brain imaging was performed in 192 patients (86.5%), including 157 magnetic resonance imaging (70.7%). Among patients with acute ischaemic cerebrovascular syndrome, 13 (22.8%) of 57 had multiterritory ischaemic strokes, with large vessel thrombosis in 16 (28.1%) of 57. Brain magnetic resonance imaging of encephalitis patients showed heterogeneous acute nonvascular lesions in 14 (66.7%) of 21. Cerebrospinal fluid of 97 patients (43.7%) was analysed, with pleocytosis found in 18 patients (18.6%) and a positive SARS-CoV-2 PCR result in two patients with encephalitis. The median (IQR) follow-up was 24 (17-34) days with a high short-term mortality rate (28/222, 12.6%). CONCLUSIONS: Clinical spectrum and outcomes of neurologic manifestations associated with SARS-CoV-2 infection were broad and heterogeneous, suggesting different underlying pathogenic processes.


Subject(s)
COVID-19/complications , Nervous System Diseases/etiology , Registries/statistics & numerical data , Aged , Brain/diagnostic imaging , Brain/pathology , COVID-19/epidemiology , Female , France/epidemiology , Humans , Male , Middle Aged , Nervous System Diseases/diagnosis , Nervous System Diseases/epidemiology , Nervous System Diseases/pathology , Retrospective Studies , SARS-CoV-2
9.
Brain Nerve ; 72(10): 1031-1037, 2020 Oct.
Article in Japanese | MEDLINE | ID: covidwho-869291

ABSTRACT

Although COVID-19 is predominantly characterized by respiratory symptoms, various types of diseases such as cerebral infarction, thrombosis, encephalitis/encephalopathy, and autoimmune disorders have been reported to be associated with COVID-19. Possible mechanisms for neurological complications of COVID-19 are 1) direct invasion of the virus into the nervous system, 2) neurological symptoms of COVID-19 as a systemic disease, 3) parainfectious neurological complications, and 4) an accidental neurological disorder during a pandemic are assumed. In this paper, encephalitis and encephalopathy have been reviewed as neuronal complications of COVID-19, discussing these pathological conditions and whether SARS-CoV-2 targets the central nervous system.


Subject(s)
Betacoronavirus , Brain Diseases , Coronavirus Infections , Meningoencephalitis , Pandemics , Pneumonia, Viral , Brain Diseases/etiology , COVID-19 , Coronavirus Infections/complications , Humans , Meningoencephalitis/etiology , Pneumonia, Viral/complications , SARS-CoV-2
10.
J Neurol ; 268(8): 2671-2675, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-841658

ABSTRACT

OBJECTIVE: To report on efficacy and safety of intravenous immunoglobulin (IVIg) therapy in a case series of patients with COVID-19-related encephalopathy. METHODS: We retrospectively collected data on all patients with COVID-19 hospitalized at two Italian hospitals who developed encephalopathy during disease course and were treated with IVIg. RESULTS: Five patients (two females, mean age 66.8 years) developed encephalopathy after a mean of 12.6 days, since the onset of respiratory/constitutional symptoms related to COVID-19. Four patients suffered severe respiratory distress, three of which required invasive mechanical ventilation. Neurological manifestations included impaired consciousness, agitation, delirium, pyramidal and extrapyramidal signs. EEG demonstrated diffuse slowing in all patients. Brain MRI showed non-specific findings. CSF analysis revealed normal cell count and protein levels. In all subjects, RT-PCR for SARS-CoV-2 in CSF tested negative. IVIg at 0.4 g/kg/die was commenced 29.8 days (mean, range: 19-55 days) after encephalopathy onset, leading to complete electroclinical recovery in all patients, with an initial improvement of neuropsychiatric symptoms observed in 3.4 days (mean, range: 1-10 days). No adverse events related to IVIg were observed. CONCLUSIONS: Our preliminary findings suggest that IVIg may represent a safe and effective treatment for COVID-19-associated encephalopathy. Clinical efficacy may be driven by the anti-inflammatory action of IVIg, associated with its anti-cytokine qualities.


Subject(s)
Brain Diseases , COVID-19 , Aged , Brain Diseases/drug therapy , Female , Humans , Immunoglobulins, Intravenous , Retrospective Studies , SARS-CoV-2
11.
J Neuroimmunol ; 349: 577400, 2020 12 15.
Article in English | MEDLINE | ID: covidwho-792960

ABSTRACT

Encephalopathy is emerging as a recurrent complication of COVID-19 yet remains poorly characterized. We report the case of a middle-aged woman with COVID-19-related encephalopathy presenting as expressive aphasia and inattentiveness, subsequently progressing to agitation and marked confusion. Brain MRI and CSF analysis were unremarkable, while EEG showed slowing with frontal sharp waves. Neuropsychiatric symptoms resolved following treatment with tocilizumab. CNS involvement in COVID-19 may present as a subacute encephalopathy characterized by prominent frontal lobe dysfunction, with language disturbances as first neurological manifestation. Future studies should further investigate the role of tocilizumab in treating COVID-19-related encephalopathy.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Aphasia/etiology , Brain Diseases/virology , COVID-19/complications , Cytokine Release Syndrome/drug therapy , Brain Diseases/drug therapy , Brain Diseases/immunology , COVID-19/immunology , Cytokine Release Syndrome/virology , Female , Humans , Middle Aged , SARS-CoV-2
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