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      Headaches and facial pain attributed to SARS‐CoV‐2 infection and vaccination: a systematic review

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          Abstract

          Background and purpose

          The aim was to provide insights to the characteristics of headache in the context of COVID‐19 on behalf of the Headache Scientific Panel and the Neuro‐COVID‐19 Task Force of the European Academy of Neurology (EAN) and the European Headache Federation (EHF).

          Methods

          Following the Delphi method the Task Force identified six relevant questions and then conducted a systematic literature review to provide evidence‐based answers and suggest specific diagnostic criteria.

          Results

          No data for facial pain were identified in the literature search. (1) Headache incidence during acute COVID‐19 varies considerably, with higher prevalence rates in prospective compared to retrospective studies (28.9%–74.6% vs. 6.5%–34.0%). (2) Acute COVID‐19 headache is usually bilateral or holocranial and often moderate to severe with throbbing pain quality lasting 2–14 days after first signs of COVID‐19; photo‐phonophobia, nausea, anosmia and ageusia are common associated features; persistent headache shares similar clinical characteristics. (3) Acute COVID‐19 headache is presumably caused by immune‐mediated mechanisms that activate the trigeminovascular system. (4) Headache occurs in 13.3%–76.9% following SARS‐CoV‐2 vaccination and occurs more often amongst women with a pre‐existing primary headache; the risk of developing headache is higher with the adenoviral‐vector‐type vaccines than with other preparations. (5) Headache related to SARS‐CoV‐2 vaccination is mostly bilateral, and throbbing, pressing, jolting or stabbing. (6) No studies have been conducted investigating the underlying mechanism of headache attributed to SARS‐CoV‐2 vaccines.

          Conclusion

          The results of this joint EAN/EHF initiative provide a framework for a better understanding of headache in the context of SARS‐CoV‐2 infection and vaccination.

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          Most cited references94

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          The PRISMA 2020 statement: an updated guideline for reporting systematic reviews

          The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, published in 2009, was designed to help systematic reviewers transparently report why the review was done, what the authors did, and what they found. Over the past decade, advances in systematic review methodology and terminology have necessitated an update to the guideline. The PRISMA 2020 statement replaces the 2009 statement and includes new reporting guidance that reflects advances in methods to identify, select, appraise, and synthesise studies. The structure and presentation of the items have been modified to facilitate implementation. In this article, we present the PRISMA 2020 27-item checklist, an expanded checklist that details reporting recommendations for each item, the PRISMA 2020 abstract checklist, and the revised flow diagrams for original and updated reviews.
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            Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition

            (2018)
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              Psychiatric and neuropsychiatric presentations associated with severe coronavirus infections: a systematic review and meta-analysis with comparison to the COVID-19 pandemic

              Summary Background Before the COVID-19 pandemic, coronaviruses caused two noteworthy outbreaks: severe acute respiratory syndrome (SARS), starting in 2002, and Middle East respiratory syndrome (MERS), starting in 2012. We aimed to assess the psychiatric and neuropsychiatric presentations of SARS, MERS, and COVID-19. Methods In this systematic review and meta-analysis, MEDLINE, Embase, PsycINFO, and the Cumulative Index to Nursing and Allied Health Literature databases (from their inception until March 18, 2020), and medRxiv, bioRxiv, and PsyArXiv (between Jan 1, 2020, and April 10, 2020) were searched by two independent researchers for all English-language studies or preprints reporting data on the psychiatric and neuropsychiatric presentations of individuals with suspected or laboratory-confirmed coronavirus infection (SARS coronavirus, MERS coronavirus, or SARS coronavirus 2). We excluded studies limited to neurological complications without specified neuropsychiatric presentations and those investigating the indirect effects of coronavirus infections on the mental health of people who are not infected, such as those mediated through physical distancing measures such as self-isolation or quarantine. Outcomes were psychiatric signs or symptoms; symptom severity; diagnoses based on ICD-10, DSM-IV, or the Chinese Classification of Mental Disorders (third edition) or psychometric scales; quality of life; and employment. Both the systematic review and the meta-analysis stratified outcomes across illness stages (acute vs post-illness) for SARS and MERS. We used a random-effects model for the meta-analysis, and the meta-analytical effect size was prevalence for relevant outcomes, I 2 statistics, and assessment of study quality. Findings 1963 studies and 87 preprints were identified by the systematic search, of which 65 peer-reviewed studies and seven preprints met inclusion criteria. The number of coronavirus cases of the included studies was 3559, ranging from 1 to 997, and the mean age of participants in studies ranged from 12·2 years (SD 4·1) to 68·0 years (single case report). Studies were from China, Hong Kong, South Korea, Canada, Saudi Arabia, France, Japan, Singapore, the UK, and the USA. Follow-up time for the post-illness studies varied between 60 days and 12 years. The systematic review revealed that during the acute illness, common symptoms among patients admitted to hospital for SARS or MERS included confusion (36 [27·9%; 95% CI 20·5–36·0] of 129 patients), depressed mood (42 [32·6%; 24·7–40·9] of 129), anxiety (46 [35·7%; 27·6–44·2] of 129), impaired memory (44 [34·1%; 26·2–42·5] of 129), and insomnia (54 [41·9%; 22·5–50·5] of 129). Steroid-induced mania and psychosis were reported in 13 (0·7%) of 1744 patients with SARS in the acute stage in one study. In the post-illness stage, depressed mood (35 [10·5%; 95% CI 7·5–14·1] of 332 patients), insomnia (34 [12·1%; 8·6–16·3] of 280), anxiety (21 [12·3%; 7·7–17·7] of 171), irritability (28 [12·8%; 8·7–17·6] of 218), memory impairment (44 [18·9%; 14·1–24·2] of 233), fatigue (61 [19·3%; 15·1–23·9] of 316), and in one study traumatic memories (55 [30·4%; 23·9–37·3] of 181) and sleep disorder (14 [100·0%; 88·0–100·0] of 14) were frequently reported. The meta-analysis indicated that in the post-illness stage the point prevalence of post-traumatic stress disorder was 32·2% (95% CI 23·7–42·0; 121 of 402 cases from four studies), that of depression was 14·9% (12·1–18·2; 77 of 517 cases from five studies), and that of anxiety disorders was 14·8% (11·1–19·4; 42 of 284 cases from three studies). 446 (76·9%; 95% CI 68·1–84·6) of 580 patients from six studies had returned to work at a mean follow-up time of 35·3 months (SD 40·1). When data for patients with COVID-19 were examined (including preprint data), there was evidence for delirium (confusion in 26 [65%] of 40 intensive care unit patients and agitation in 40 [69%] of 58 intensive care unit patients in one study, and altered consciousness in 17 [21%] of 82 patients who subsequently died in another study). At discharge, 15 (33%) of 45 patients with COVID-19 who were assessed had a dysexecutive syndrome in one study. At the time of writing, there were two reports of hypoxic encephalopathy and one report of encephalitis. 68 (94%) of the 72 studies were of either low or medium quality. Interpretation If infection with SARS-CoV-2 follows a similar course to that with SARS-CoV or MERS-CoV, most patients should recover without experiencing mental illness. SARS-CoV-2 might cause delirium in a significant proportion of patients in the acute stage. Clinicians should be aware of the possibility of depression, anxiety, fatigue, post-traumatic stress disorder, and rarer neuropsychiatric syndromes in the longer term. Funding Wellcome Trust, UK National Institute for Health Research (NIHR), UK Medical Research Council, NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust and University College London.
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                Author and article information

                Contributors
                dmitsikostas@uoa.gr
                Journal
                Eur J Neurol
                Eur J Neurol
                10.1111/(ISSN)1468-1331
                ENE
                European Journal of Neurology
                John Wiley and Sons Inc. (Hoboken )
                1351-5101
                1468-1331
                28 February 2024
                June 2024
                : 31
                : 6 ( doiID: 10.1111/ene.v31.6 )
                : e16251
                Affiliations
                [ 1 ] Neurology Department, Aeginition Hospital, Medical School National & Kapodistrian University of Athens Athens Greece
                [ 2 ] Headache Unit, Neurology Department Hospital Universitari Vall d'Hebron Barcelona Spain
                [ 3 ] Headache and Neurological Pain Research Group, Department of Medicine Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona Barcelona Spain
                [ 4 ] Neurophysiopathology Unit, DiBrain Department Aldo Moro University Bari Italy
                [ 5 ] Athens Naval Hospital Athens Greece
                [ 6 ] Department of Neurology, Faculty of Medicine Istanbul University, Istanbul Istanbul Turkey
                [ 7 ] Department of Neurology and Algology, NÖROM Gazi University Ankara Ankara Turkey
                [ 8 ] Department of Neurology University Hospital Schleswig‐Holstein Lübeck Germany
                [ 9 ] Department of Neurology Akershus University Hospital Lørenskog Norway
                [ 10 ] NorHEAD, Norwegian Centre for Headache Research Akershus University Hospital Lørenskog Norway
                [ 11 ] Department of General Practice, HELSAM University of Oslo Oslo Norway
                [ 12 ] Department of Neurology and Stroke Unit Konventhospital Barmherzige Brüder Linz Linz Austria
                [ 13 ] Headache Medical Center Linz Linz Austria
                [ 14 ] Division of Neurology, CHU of Grenoble, Grenoble Institute of Neurosciences, Grenoble Alpes University Grenoble France
                [ 15 ] Department of Neurology Landesklinikum Mistelbach‐Gänserndorf Mistelbach Austria
                [ 16 ] Department of Neurology Leiden University Medical Center Leiden The Netherlands
                [ 17 ] Neurology Department Clinica Universidad de Navarra Pamplona Spain
                Author notes
                [*] [* ] Correspondence

                Dimos‐Dimtirios D. Mitsikostas, First Neurology Department, Aeginition Hospital, Medical School, National and Kapodistrian Universtiy of Athens, Athens, Greece.

                Email: dmitsikostas@ 123456uoa.gr

                Author information
                https://orcid.org/0000-0002-4691-3388
                https://orcid.org/0000-0001-5525-0267
                https://orcid.org/0000-0001-6567-5373
                https://orcid.org/0000-0002-6208-1059
                https://orcid.org/0000-0002-4904-9994
                https://orcid.org/0000-0002-3357-7733
                https://orcid.org/0000-0002-8999-5424
                https://orcid.org/0000-0003-1756-1181
                https://orcid.org/0000-0002-7968-5908
                https://orcid.org/0000-0003-0796-4702
                https://orcid.org/0000-0001-8749-5533
                https://orcid.org/0000-0003-3140-6882
                https://orcid.org/0000-0002-7238-0036
                Article
                ENE16251 EJoN-23-1912.R1
                10.1111/ene.16251
                11235838
                38415282
                78a7fd21-f95b-4328-bdc4-f61b498e3b69
                © 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 January 2024
                : 12 September 2023
                : 01 February 2024
                Page count
                Figures: 1, Tables: 1, Pages: 13, Words: 9263
                Categories
                Review Article
                Headache
                Custom metadata
                2.0
                June 2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.4.5 mode:remove_FC converted:08.07.2024

                Neurology
                chronic daily headache,headache,neurological disorders
                Neurology
                chronic daily headache, headache, neurological disorders

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