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      Transcranial direct current stimulation for post-COVID fatigue: a randomized, double-blind, controlled pilot study

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          Abstract

          Fatigue is one of the most frequent and disabling symptoms of the post-COVID syndrome. In this study, we aimed to assess the effects of transcranial direct current stimulation on fatigue severity in a group of patients with post-COVID syndrome and chronic fatigue. We conducted a double-blind, parallel-group, sham-controlled study to evaluate the short-term effects of anodal transcranial direct current stimulation (2 mA, 20 min/day) on the left dorsolateral prefrontal cortex. The modified fatigue impact scale score was used as the primary endpoint. Secondary endpoints included cognition (Stroop test), depressive symptoms (Beck depression inventory) and quality of life (EuroQol-5D). Patients received eight sessions of transcranial direct current stimulation and were evaluated at baseline, immediately after the last session, and one month later. Forty-seven patients were enrolled (23 in the active treatment group and 24 in the sham treatment group); the mean age was 45.66 ± 9.49 years, and 37 (78.72%) were women. The mean progression time since the acute infection was 20.68 ± 6.34 months. Active transcranial direct current stimulation was associated with a statistically significant improvement in physical fatigue at the end of treatment and 1 month as compared with sham stimulation. No significant effect was detected for cognitive fatigue. In terms of secondary outcomes, active transcranial direct current stimulation was associated with an improvement in depressive symptoms at the end of treatment. The treatment had no effects on the quality of life. All the adverse events reported were mild and transient, with no differences between the active stimulation and sham stimulation groups. In conclusion, our results suggest that transcranial direct current stimulation on the dorsolateral prefrontal cortex may improve physical fatigue. Further studies are needed to confirm these findings and optimize stimulation protocols.

          Abstract

          In a randomized, double-blind, parallel-group and sham-controlled study, Oliver-Mas et al. find that eight sessions of anodal transcranial direct current stimulation on the left prefrontal dorsolateral cortex improve physical fatigue in patients with the post-COVID syndrome, with no adverse events.

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          Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L)

          Purpose This article introduces the new 5-level EQ-5D (EQ-5D-5L) health status measure. Methods EQ-5D currently measures health using three levels of severity in five dimensions. A EuroQol Group task force was established to find ways of improving the instrument’s sensitivity and reducing ceiling effects by increasing the number of severity levels. The study was performed in the United Kingdom and Spain. Severity labels for 5 levels in each dimension were identified using response scaling. Focus groups were used to investigate the face and content validity of the new versions, including hypothetical health states generated from those versions. Results Selecting labels at approximately the 25th, 50th, and 75th centiles produced two alternative 5-level versions. Focus group work showed a slight preference for the wording ‘slight-moderate-severe’ problems, with anchors of ‘no problems’ and ‘unable to do’ in the EQ-5D functional dimensions. Similar wording was used in the Pain/Discomfort and Anxiety/Depression dimensions. Hypothetical health states were well understood though participants stressed the need for the internal coherence of health states. Conclusions A 5-level version of the EQ-5D has been developed by the EuroQol Group. Further testing is required to determine whether the new version improves sensitivity and reduces ceiling effects.
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            A clinical case definition of post-COVID-19 condition by a Delphi consensus

            People with COVID-19 might have sustained postinfection sequelae. Known by a variety of names, including long COVID or long-haul COVID, and listed in the ICD-10 classification as post-COVID-19 condition since September, 2020, this occurrence is variable in its expression and its impact. The absence of a globally standardised and agreed-upon definition hampers progress in characterisation of its epidemiology and the development of candidate treatments. In a WHO-led Delphi process, we engaged with an international panel of 265 patients, clinicians, researchers, and WHO staff to develop a consensus definition for this condition. 14 domains and 45 items were evaluated in two rounds of the Delphi process to create a final consensus definition for adults: post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning. Symptoms might be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms might also fluctuate or relapse over time. A separate definition might be applicable for children. Although the consensus definition is likely to change as knowledge increases, this common framework provides a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy.
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              SARS-CoV-2 is associated with changes in brain structure in UK Biobank

              There is strong evidence of brain-related abnormalities in COVID-19 1–13 . However, it remains unknown whether the impact of SARS-CoV-2 infection can be detected in milder cases, and whether this can reveal possible mechanisms contributing to brain pathology. Here we investigated brain changes in 785 participants of UK Biobank (aged 51–81 years) who were imaged twice using magnetic resonance imaging, including 401 cases who tested positive for infection with SARS-CoV-2 between their two scans—with 141 days on average separating their diagnosis and the second scan—as well as 384 controls. The availability of pre-infection imaging data reduces the likelihood of pre-existing risk factors being misinterpreted as disease effects. We identified significant longitudinal effects when comparing the two groups, including (1) a greater reduction in grey matter thickness and tissue contrast in the orbitofrontal cortex and parahippocampal gyrus; (2) greater changes in markers of tissue damage in regions that are functionally connected to the primary olfactory cortex; and (3) a greater reduction in global brain size in the SARS-CoV-2 cases. The participants who were infected with SARS-CoV-2 also showed on average a greater cognitive decline between the two time points. Importantly, these imaging and cognitive longitudinal effects were still observed after excluding the 15 patients who had been hospitalised. These mainly limbic brain imaging results may be the in vivo hallmarks of a degenerative spread of the disease through olfactory pathways, of neuroinflammatory events, or of the loss of sensory input due to anosmia. Whether this deleterious effect can be partially reversed, or whether these effects will persist in the long term, remains to be investigated with additional follow-up.
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                Author and article information

                Contributors
                Journal
                Brain Commun
                Brain Commun
                braincomms
                Brain Communications
                Oxford University Press (US )
                2632-1297
                2023
                10 April 2023
                10 April 2023
                : 5
                : 2
                : fcad117
                Affiliations
                Department of Neurology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid , 28040 Madrid, Spain
                Department of Neurology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid , 28040 Madrid, Spain
                Department of Neurology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid , 28040 Madrid, Spain
                Department of Neurology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid , 28040 Madrid, Spain
                Department of Neurology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid , 28040 Madrid, Spain
                Department of Neurology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid , 28040 Madrid, Spain
                Department of Neurology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid , 28040 Madrid, Spain
                Department of Neurology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid , 28040 Madrid, Spain
                Department of Radiology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid , 28040 Madrid, Spain
                Department of Neurology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid , 28040 Madrid, Spain
                Department of Radiology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid , 28040 Madrid, Spain
                Department of Neurology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid , 28040 Madrid, Spain
                Department of Neurology, Hospital Clínico San Carlos, San Carlos Health Research Institute (IdISCC), Universidad Complutense de Madrid , 28040 Madrid, Spain
                Author notes
                Correspondence to: Jordi A. Matias-Guiu Department of Neurology, Hospital Clínico San Carlos C/Profesor Martín Lagos, 28040 Madrid, Spain E-mails: jordimatiasguiu@ 123456hotmail.com ; jordi.matias-guiu@ 123456salud.madrid.org
                Author information
                https://orcid.org/0000-0001-5520-2708
                Article
                fcad117
                10.1093/braincomms/fcad117
                10116605
                37091591
                1b703cb4-4ed3-4d7b-9f4a-2095bbbbf6cd
                © The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 October 2022
                : 19 February 2023
                : 05 April 2023
                Page count
                Pages: 12
                Funding
                Funded by: Fundación para el Conocimiento madri + d, doi 10.13039/501100007245;
                Funded by: Instituto de Salud Carlos III, doi 10.13039/501100004587;
                Funded by: European Regional Development Fund, doi 10.13039/501100008530;
                Categories
                Original Article
                AcademicSubjects/MED00310
                AcademicSubjects/SCI01870

                covid-19,post-covid syndrome,brain stimulation,fatigue,cognitive

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