| 1. |
- Fällmar, David, et al.
(författare)
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The extent of neuroradiological findings in COVID-19 shows correlation with blood biomarkers, Glasgow coma scale score and days in intensive care
- 2022
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Ingår i: Journal of neuroradiology. - : Elsevier. - 0150-9861 .- 1773-0406. ; 49:6, s. 421-427
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeA 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 methodsPatients 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 conclusionsThe 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.
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| 2. |
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| 3. |
- Virhammar, Johan, et al.
(författare)
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Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid
- 2020
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Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 95:10, s. 445-449
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Tidskriftsartikel (refereegranskat)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.
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| 4. |
- Abdelhak, Ahmed, et al.
(författare)
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Prognostic performance of blood neurofilament light chain protein in hospitalized COVID-19 patients without major central nervous system manifestations: an individual participant data meta-analysis.
- 2023
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Ingår i: Journal of neurology. - : Springer. - 1432-1459 .- 0340-5354. ; 270:7, s. 3315-3328
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Tidskriftsartikel (refereegranskat)abstract
- To investigate the prognostic value of blood neurofilament light chain protein (NfL) levels in the acute phase of coronavirus disease 2019 (COVID-19).We conducted an individual participant data (IPD) meta-analysis after screening on MEDLINE and Scopus to May 23rd2022. We included studies with hospitalized adult COVID-19 patients without major COVID-19-associated central nervous system (CNS) manifestations and with a measurement of blood NfL in the acute phase as well as data regarding at least one clinical outcome including intensive care unit (ICU)admission, need of mechanical ventilation (MV) and death. We derived the age-adjusted measures NfL Z scores and conducted mixed-effects modelling to test associations between NfL Z scores and other variables, encompassing clinical outcomes. Summary receiver operating characteristic curves (SROCs) were used to calculate the area under the curve (AUC) for blood NfL.We identified 382 records, of which 7 studies were included with a total of 669 hospitalized COVID-19 cases (mean age 66.2±15.0years, 68.1% males). Median NfL Z score at admission was elevated compared to the age-corrected reference population (2.37, IQR: 1.13-3.06, referring to 99th percentile in healthy controls). NfL Z scores were significantly associated with disease duration and severity. Higher NfL Z scores were associated with ahigher likelihood of ICU admission, need ofMV, and death. SROCs revealed AUCs of 0.74, 0.80 and 0.71 for mortality, need ofMV and ICU admission, respectively.Blood NfL levels were elevated in the acute phase of COVID-19 patients without major CNS manifestations and associated with clinical severity and poor outcome. The marker might ameliorate the performance of prognostic multivariable algorithms in COVID-19.
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| 5. |
- Banote, Rakesh Kumar, et al.
(författare)
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Quantitative proteomic analysis to identify differentially expressed proteins in patients with epilepsy
- 2021
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211 .- 1872-6844. ; 174
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Tidskriftsartikel (refereegranskat)abstract
- There is a great need for biomarkers in epilepsy, particularly markers of epileptogenesis. A first seizure will lead to epilepsy in 20-45 % of cases, but biomarkers that can identify these individuals are missing. The purpose of this study was to identify potential biomarkers of epilepsy/epileptogenesis in a cohort of adults with new-onset seizures, using quantitative proteomic analysis. Plasma was collected from 55 adults with new-onset seizures and sufficient follow-up to identify epilepsy. After a follow up period of two years, 63.6 % of the cohort had a diagnosis of epilepsy, whereas 36.4 % of patients only had a single seizure. Plasma proteins were extracted and labelled with tandem mass tags, then analyzed using mass spectrometry approach. Proteins that were up- or downregulated by >= 20 % and with a pvalue of <0.05 were considered as differentially expressed and were also annotated to their processes and pathways. Several proteins were differentially expressed in the epilepsy group compared to controls. A total of 1075 proteins were detected, out of which 41 proteins were found to be significantly dysregulated in epilepsy patients. Many of these have been identified in experimental studies of epilepogenesis. We report plasma proteome profiling in new-onset epilepsy in a pilot study with 55 individuals. The identified proteins could be involved in pathways associated with epileptogenesis. The results should be seen as hypothesisgenerating and targeted, confirmatory studies are needed.
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| 6. |
- Bergerum, Carolina, 1967-
(författare)
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Patient and public involvement in hospital quality improvement interventions : the mechanisms, monitoring and management
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This dissertation focuses on the mechanisms, monitoring and management of patient and public involvement in hospital quality improvement (QI) interventions. Findings from a literature review generated an initial programme theory (PT) on active patient involvement in healthcare QI interventions (Paper 1). Empirical studies were also undertaken in order to describe what was actually happening in the hospital QI teams and what patients and professionals experience influence their joint involvement (Paper 2), and to compare hospital leaders’ and managers’ experiences of managing QI interventions involving patients and the public (Paper 3). Finally, it was studied how patient-reported measures stimulate patient involvement in QI interventions in practice (Paper 4). The research had a qualitative design. The approach was descriptive and comparative, and the studies were carried out prospectively. Data were collected in two hospital organisations in Sweden and in one hospital organisation in the Netherlands. Data collection methods were a literature search (Paper 1), interviews and field observations (Paper 2 and 3) and data collection meetings (Paper 4). Altogether, 93 team meetings and meetings between the team leaders and management were attended and a total of 20 days of study visits with different forms of meetings were made. Twelve patients, 12 healthcare professionals and 17 and 8 hospital leaders and managers, respectively, participated in the interviews and data collection meetings. Realist synthesis was used to formulate the initial PT (Paper 1). Constructivist grounded theory was used to analyse and describe what was happening in the QI teams and how it was experienced by the team members (Paper 2). To compare hospital leaders’ and managers’ different, contextual meanings in Sweden and the Netherlands, the reflexive thematic analysis informed by critical realism was used (Paper 3). To order, manage and map data from 31 examples of local QI interventions associated to patient-reported measures, the framework method was used (Paper 4). The results formulate a generic PT on the mechanisms, monitoring and management perspectives of co-produced QI interventions in hospital services where patients and the public are involved. The PT provides a hypothesis on the various mechanisms at play and outcomes obtained at the different levels of hospital organisations in the process. It is argued that focus should be on experiences, interaction, relationships and dialogue, integration of context, and the matching of hospital resources to patient and public demands and needs. Subsequently, the outcome will be the resources and reasoning interplay resulting in actions and processes, experiences and knowledge, ‘product’ benefits, emotions, judgements and motivations. Monitoring constitutes an important feedback loop to enable such learnings. The PT aligns the perspectives of the clinical microsystem, improvement science and the service-dominant logic, and has a potential to explain how patient and public involvement in QI interventions might work.
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| 7. |
- Cunningham, Janet, et al.
(författare)
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Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in the Serum and Cerebrospinal Fluid of Patients With Coronavirus Disease 2019 and Neurological Symptoms
- 2022
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 225:6, s. 965-970
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Tidskriftsartikel (refereegranskat)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.
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| 8. |
- Cunningham, Janet L, et al.
(författare)
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Anti-SARS-CoV2 antibody responses in serum and cerebrospinal fluid of COVID-19 patients with neurological symptoms.
- 2022
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 225:6, s. 965-970
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Tidskriftsartikel (refereegranskat)abstract
- Antibody responses to SARS-CoV-2 in serum and CSF from 16 COVID-19 patients with neurological symptoms were assessed using two independent methods. IgG specific for the virus spike protein was found in 81% of cases in serum and in 56% in CSF. SARS-CoV-2 IgG in CSF was observed in two cases with negative serology. Levels of IgG in both serum and CSF were associated with disease severity (p<0.05). All patients with elevated markers of CNS damage in CSF also had CSF antibodies (p=0.002), and CSF antibodies had the highest predictive value for neuronal damage markers of all tested clinical variables.
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| 9. |
- Fahlström, Markus, et al.
(författare)
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Evaluation of Arterial Spin Labeling MRI : Comparison with 15O-Water PET on an Integrated PET/MR Scanner
- 2021
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Ingår i: Diagnostics (Basel). - : MDPI. - 2075-4418. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral blood flow (CBF) measurements are of high clinical value and can be acquired non-invasively with no radiation exposure using pseudo-continuous arterial spin labeling (ASL). The aim of this study was to evaluate accordance in resting state CBF between ASL (CBFASL) and 15O-water positron emission tomography (PET) (CBFPET) acquired simultaneously on an integrated 3T PET/MR system. The data comprised ASL and dynamic 15O-water PET data with arterial blood sampling of eighteen subjects (eight patients with focal epilepsy and ten healthy controls, age 21 to 61 years). 15O-water PET parametric CBF images were generated using a basis function implementation of the single tissue compartment model. Cortical and subcortical regions were automatically segmented using Freesurfer. Average CBFASL and CBFPET in grey matter were 60 ± 20 and 75 ± 22 mL/100 g/min respectively, with a relatively high correlation (r = 0.78, p < 0.001). Bland-Altman analysis revealed poor agreement (bias = −15 mL/100 g/min, lower and upper limits of agreements = −16 and 45 mL/100 g/min, respectively) with a negative relationship. Accounting for the negative relationship, the width of the limits of agreement could be narrowed from 61 mL/100 g/min to 35 mL/100 g/min using regression-based limits of agreements. Although a high correlation between CBFASL and CBFPET was found, the agreement in absolute CBF values was not sufficient for ASL to be used interchangeably with 15O-water PET.
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| 10. |
- Frithiof, Robert, et al.
(författare)
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Critical illness polyneuropathy, myopathy and neuronal biomarkers in COVID-19 patients: A prospective study
- 2021
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Ingår i: Clinical Neurophysiology. - : Elsevier BV. - 1388-2457 .- 1872-8952. ; 132:7, s. 1733-1740
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Tidskriftsartikel (refereegranskat)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. (c) 2021 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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