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1.
Crit Care Explor ; 2(8): e0197, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-1795077

ABSTRACT

We describe the intracranial pressure dynamics and cerebral vasomotor reactivity in a coronavirus disease 2019 patient with acute encephalitis treated with cerebrospinal fluid drainage and therapeutic plasma exchange. DATA SOURCES: Coronavirus disease ICU, Uppsala University Hospital, Sweden. STUDY SELECTION: Case report. DATA EXTRACTION: Radiology, intracranial pressure, intracranial compliance (correlation between intracranial pressure amplitude and mean intracranial pressure), cerebral vasomotor reactivity (pressure reactivity index), arterial blood pressure, cerebrospinal fluid chemistry, and treatment. DATA SYNTHESIS: None. CONCLUSIONS: This is the first reported case of intracranial pressure monitoring in a patient with acute encephalitis following coronavirus disease 2019. Intracranial pressure data exhibited a high incidence of plateau waves with intracranial pressure insults above 40 mm Hg that required cerebrospinal fluid drainage. Intracranial compliance was low, and pressure reactivity was intact. It is probable that the combination of low intracranial compliance and intact pressure autoregulation explain the high degree of plateau intracranial pressure waves and intracranial pressure variability. This case illustrates that it could be of value to consider intracranial pressure monitoring in selected coronavirus disease 2019 patients with suspicion of increased intracranial pressure to be able to confirm and treat intracranial hypertension if needed. In this patient, therapeutic plasma exchange was safe and efficacious as the level of neuroinflammation decreased and the patient regained consciousness.

2.
J Infect Dis ; 225(6): 965-970, 2022 03 15.
Article in English | MEDLINE | ID: covidwho-1740882

ABSTRACT

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in serum and cerebrospinal fluid (CSF) samples from 16 patients with coronavirus disease 2019 and neurological symptoms were assessed using 2 independent methods. Immunoglobulin G (IgG) specific for the virus spike protein was found in 81% of patients in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in 2 patients with negative serological findings. Levels of IgG in both serum and CSF were associated with disease severity (P < .05). All patients with elevated markers of central nervous system damage in CSF also had CSF antibodies (P = .002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.


Subject(s)
Antibodies, Viral/blood , COVID-19/diagnosis , Immunoglobulin G/blood , Nervous System Diseases/blood , Nervous System Diseases/cerebrospinal fluid , SARS-CoV-2/isolation & purification , Aged , Antibodies, Neutralizing/blood , Antibody Formation , Biomarkers/blood , Biomarkers/cerebrospinal fluid , COVID-19/blood , COVID-19/cerebrospinal fluid , COVID-19/complications , Female , Humans , Male , Middle Aged , Nervous System Diseases/diagnosis , Nervous System Diseases/etiology , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Spike Glycoprotein, Coronavirus
3.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-310699

ABSTRACT

Background: Several reports on neurological complications associated with SARS-CoV-2 infection have been published. However, systematic description on intensive care unit acquired weakness (ICUAW) are still missing. Methods: : The objective was to determine the incidence and characteristics of critical illness polyneuropathy (CIN) and myopathy (CIM) in patients with severe COVID-19. We also aimed to describe the electrophysiological features and their relation to plasma biomarkers for neuronal injury. This was a prospective observational intensive care unit cohort study. All adult patients admitted to the general intensive care unit (ICU) at Uppsala University Hospital, Uppsala, Sweden, between March 13 and June 8, 2020 were screened for inclusion. Patients with PCR confirmed COVID-19 were included. All patients were admitted to intensive care treatment due to severe COVID-19, including intravenous anaesthesia, opioid anaelgesia, neuromuscular blockade and mechanical ventilation. Associations of clinical, electrophysiological (sensory and motor conduction studies and electromyography) and biomarker data [neurofilament light chain (NfL), glial fibrillary acidic protein (GFAp) and tau] were studied between COVID-19 patients who developed CIN/CIM and those who did not. Results: : 111 COVID-19 patients were included, 11 (11 males, mean age: 64 years) developed CIN/CIM whereas 100 (74 males, mean age: 61 years) did not (non-CIN/CIM). The CIN/CIM incidence was higher in COVID-19 patients compared to a general ICU-population treated during 2019 (9.9% vs 3.4%). In particular CIN was more frequent in the COVID-19 ICU cohort (50%) compared with the non-COVID-19 ICU cohort (0%, p=0.008). NfL and GFAp levels were higher in the CIN/CIM group both at the early (<9 days) and late time points (>11 days) compared with the non-CIN/CIM group (both p=0.001) and correlated with nerve amplitudes. Conclusions: : CIN/CIM, in particular CIN, were more prevalent among COVID-19 patients than an ICU treated control cohort and should be considered in the differential diagnostic workup and the further rehabilitation of COVID-19 patients. COVID-19 patients who later developed ICUAW had significantly higher NfL and GFAp in the early phase of ICU care, which suggests their potential as predictive biomarkers. Trial registration: The study protocol was registered (ClinicalTrialsID:NCT04316884). Mechanisms for Organ Dysfunction in Covid-19 (UMODCOVID19) March 18, 2020.

4.
J Neuroradiol ; 2021 Nov 18.
Article in English | MEDLINE | ID: covidwho-1521436

ABSTRACT

BACKGROUND AND PURPOSE: A wide range of neuroradiological findings has been reported in patients with coronavirus disease 2019 (COVID-19), ranging from subcortical white matter changes to infarcts, haemorrhages and focal contrast media enhancement. These have been descriptively but inconsistently reported and correlations with clinical findings and biomarkers have been difficult to extract from the literature. The purpose of this study was to quantify the extents of neuroradiological findings in a cohort of patients with COVID-19 and neurological symptoms, and to investigate correlations with clinical findings, duration of intensive care and biomarkers in blood. MATERIAL AND METHODS: Patients with positive SARS-CoV-2 and at least one new-onset neurological symptom were included from April until July 2020. Nineteen patients were examined regarding clinical symptoms, biomarkers in blood and MRI of the brain. In order to quantify the MRI findings, a semi-quantitative neuroradiological severity scale was constructed a priori, and applied to the MR images by two specialists in neuroradiology. RESULTS AND CONCLUSIONS: The score from the severity scale correlated significantly with blood biomarkers of CNS injury (glial fibrillary acidic protein, total-tau, ubiquitin carboxyl-terminal hydrolase L1) and inflammation (C-reactive protein), Glasgow Coma Scale score, and the number of days spent in intensive care. The underlying radiological assessments had inter-rater agreements of 90.5%/86% (for assessments with 2/3 alternatives). Total intraclass correlation was 0.80. Previously reported neuroradiological findings in COVID-19 have been diverse and heterogenous. In this study, the extent of findings in MRI examination of the brain, quantified using a structured report, shows correlation with relevant biomarkers.

6.
Clin Neurophysiol ; 132(7): 1733-1740, 2021 07.
Article in English | MEDLINE | ID: covidwho-1163547

ABSTRACT

OBJECTIVE: The aim was to characterize the electrophysiological features and plasma biomarkers of critical illness polyneuropathy (CIN) and myopathy (CIM) in coronavirus disease 2019 (COVID-19) patients with intensive care unit acquired weakness (ICUAW). METHODS: An observational ICU cohort study including adult patients admitted to the ICU at Uppsala University Hospital, Uppsala, Sweden, from March 13th to June 8th 2020. We compared the clinical, electrophysiological and plasma biomarker data between COVID-19 patients who developed CIN/CIM and those who did not. Electrophysiological characteristics were also compared between COVID-19 and non-COVID-19 ICU patients. RESULTS: 111 COVID-19 patients were included, 11 of whom developed CIN/CIM. Patients with CIN/CIM had more severe illness; longer ICU stay, more thromboembolic events and were more frequently treated with invasive ventilation for longer than 2 weeks. In particular CIN was more frequent among COVID-19 patients with ICUAW (50%) compared with a non-COVID-19 cohort (0%, p = 0.008). Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAp) levels were higher in the CIN/CIM group compared with those that did not develop CIN/CIM (both p = 0.001) and correlated with nerve amplitudes. CONCLUSIONS: CIN/CIM was more prevalent among COVID-19 ICU patients with severe illness. SIGNIFICANCE: COVID-19 patients who later developed CIN/CIM had significantly higher NfL and GFAp in the early phase of ICU care, suggesting their potential as predictive biomarkers for CIN/CIM.


Subject(s)
COVID-19/complications , Muscular Diseases/etiology , Polyneuropathies/etiology , Aged , Biomarkers/blood , COVID-19/physiopathology , Critical Illness , Female , Humans , Intensive Care Units , Length of Stay/statistics & numerical data , Male , Middle Aged , Muscle Weakness/etiology , Muscular Diseases/blood , Muscular Diseases/physiopathology , Polyneuropathies/blood , Polyneuropathies/physiopathology , Prospective Studies , Respiration, Artificial/statistics & numerical data , Thromboembolism/etiology
8.
Eur J Neurol ; 28(10): 3324-3331, 2021 10.
Article in English | MEDLINE | ID: covidwho-1035403

ABSTRACT

BACKGROUND AND PURPOSE: Neurological symptoms have been frequently reported in hospitalized patients with coronavirus disease 2019 (COVID-19), and biomarkers of central nervous system (CNS) injury are reported to be increased in plasma but not extensively studied in cerebrospinal fluid (CSF). This study examined CSF for biomarkers of CNS injury and other pathology in relation to neurological symptoms and disease severity in patients with neurological manifestations of COVID-19. METHODS: Nineteen patients with neurological symptoms and mild to critical COVID-19 were prospectively included. Extensive analysis of CSF, including measurement of biomarkers of CNS injury (neurofilament light chain [NfL] protein, glial fibrillary acidic protein [GFAp], and total tau), was performed and compared to neurological features and disease severity. RESULTS: Neurological symptoms included altered mental status (42%), headache (42%), and central (21%) and peripheral weakness (32%). Two patients demonstrated minor pleocytosis, and four patients had increased immunoglobulin G levels in CSF. Neuronal autoantibody testing using commercial tests was negative in all patients. Increased CSF levels of NfL protein, total tau, and GFAp were seen in 63%, 37%, and 16% of patients, respectively. Increased NfL protein correlated with disease severity, time in intensive care, and level of consciousness. NfL protein in CSF was higher in patients with central neurological symptoms. CONCLUSIONS: Although limited by the small sample size, our data suggest that levels of NfL protein, GFAp, and total tau in CSF are commonly elevated in patients with COVID-19 with neurological symptoms. This is in contrast to the standard CSF workup where pathological findings are scarce. NfL protein, in particular, is associated with central neurological symptoms and disease severity.


Subject(s)
COVID-19 , Neurofilament Proteins , Biomarkers , Central Nervous System , Glial Fibrillary Acidic Protein , Humans , SARS-CoV-2 , Severity of Illness Index
9.
Neurology ; 95(10): 445-449, 2020 09 08.
Article in English | MEDLINE | ID: covidwho-999777

ABSTRACT

Here, we report a case of COVID-19-related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.


Subject(s)
Brain/diagnostic imaging , Coronavirus Infections/cerebrospinal fluid , Leukoencephalitis, Acute Hemorrhagic/cerebrospinal fluid , Pneumonia, Viral/cerebrospinal fluid , RNA, Viral/cerebrospinal fluid , Acyclovir/therapeutic use , Antiviral Agents/therapeutic use , Betacoronavirus/genetics , COVID-19 , Coronavirus Infections/diagnostic imaging , Coronavirus Infections/physiopathology , Coronavirus Infections/therapy , Female , Glial Fibrillary Acidic Protein/cerebrospinal fluid , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunologic Factors/therapeutic use , Interleukin-6/cerebrospinal fluid , Leukoencephalitis, Acute Hemorrhagic/diagnostic imaging , Leukoencephalitis, Acute Hemorrhagic/physiopathology , Leukoencephalitis, Acute Hemorrhagic/therapy , Magnetic Resonance Imaging , Middle Aged , Neurofilament Proteins/cerebrospinal fluid , Pandemics , Plasma Exchange , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/physiopathology , Pneumonia, Viral/therapy , Real-Time Polymerase Chain Reaction , SARS-CoV-2 , Tomography, X-Ray Computed , Viral Tropism , tau Proteins/cerebrospinal fluid
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