Top

Published in:

Open Access 16-02-2024 | Glucocorticoid | Neurology and Preclinical Neurological Studies - Original Article

High-dose glucocorticoids in COVID-19 patients with acute encephalopathy: clinical and imaging findings in a retrospective cohort study

Authors: Alexandra Rhally, Giulia Bommarito, Marjolaine Uginet, Gautier Breville, Patrick Stancu, Alice Accorroni, Frédéric Assal, Patrice H. Lalive, Karl-Olof Lövblad, Gilles Allali

Published in: Journal of Neural Transmission | Issue 4/2024

Abstract

Objectives

Acute encephalopathy (AE) has been described as a severe complication of COVID-19. Inflammation has been suggested as a pathogenic mechanism, with high-dose glucocorticoids (GC) showing a beneficial effect. Here, we retrospectively analyzed the clinical and radiological features in a group of COVID-19 AE patients who received GC treatment (GT) and in a non-treated (NT) group.

Method

Thirty-six patients with COVID-19 AE (mean age 72.6 \(\pm\) 11 years; 86.11% men) were evaluated for GC treatment. Twelve patients (mean age 73.6 \(\pm\) 4.5 years; 66.67% men) received GC, whereas 24 patients who showed signs of spontaneous remission were not treated with GC (mean age 70.1 \(\pm\) 8.6 years; 95.83% men). Differences in clinical characteristics and correlations with imaging features were explored.

Results

The GT group showed signs of vulnerability, with a longer hospitalization (p = 0.009) and AE duration (p = 0.012) and a higher hypertensive arteriopathy (HTNA) score (p = 0.022), when compared to NT group. At hospital discharge, the two groups were comparable in terms of clinical outcome (modified Rankin scale; p = 0.666) or mortality (p = 0.607). In our whole group analyses, AE severity was positively correlated with periventricular white matter hyperintensities (p = 0.011), deep enlarged perivascular spaces (p = 0.039) and HTNA score (p = 0.014).

Conclusion

This study suggests that, despite signs of radiological vulnerability and AE severity, patients treated by high-dose GC showed similar outcome at discharge, with respect to NT patients. Imaging features of cerebral small vessel disease correlated with AE severity, supporting the hypothesis that brain structural vulnerability can impact AE in COVID-19.

Agarwal S, Jain R, Dogra S et al (2020) Cerebral microbleeds and leukoencephalopathy in critically Ill patients with COVID-19. Stroke 51(9):2649–2655. https://doi.org/10.1161/STROKEAHA.120.030940CrossRefPubMedPubMedCentral

Awada HN, Steinthorsdottir KJ, Schultz NA et al (2022) High-dose pre-operative glucocorticoid for prevention of emergence and postoperative delirium in liver resection: a double-blinded randomized clinical trial substudy. Acta Anaesthesiol Scand 66(6):696–703. https://doi.org/10.1111/aas.14057CrossRefPubMedPubMedCentral

Bernard-Valnet R, Perriot S, Canales M et al (2021) Encephalopathies associated with severe COVID-19 present neurovascular unit alterations without evidence for strong neuroinflammation. Neurol Neuroimmunol Neuroinflamm 8(5):e1029. https://doi.org/10.1212/NXI.0000000000001029CrossRefPubMedPubMedCentral

Bommarito G, Garibotto V, Frisoni GB, Assal F, Lalive PH, Allali G (2023) The two-way route between delirium disorder and dementia: insights from Covid-19. Neurodegener Dis. https://doi.org/10.1159/000530566. (Published online April 13)CrossRef

Damanti S, Bozzolo E, Franchini S et al (2023) Predictors and outcomes of delirium in the emergency department during the first wave of the COVID-19 pandemic in Milan. Emerg Med J 40(3):202–209. https://doi.org/10.1136/emermed-2021-211749CrossRefPubMed

Fajgenbaum DC, June CH (2020) Cytokine storm. N Engl J Med 383(23):2255–2273. https://doi.org/10.1056/NEJMra2026131CrossRefPubMedPubMedCentral

Fazekas F, Barkhof F, Wahlund LO et al (2002) CT and MRI rating of white matter lesions. Cerebrovasc Dis 13(Suppl 2):31–36. https://doi.org/10.1159/000049147CrossRefPubMed

Gregoire SM, Chaudhary UJ, Brown MM et al (2009) The Microbleed Anatomical Rating Scale (MARS): reliability of a tool to map brain microbleeds. Neurology 73(21):1759–1766. https://doi.org/10.1212/WNL.0b013e3181c34a7dCrossRefPubMed

Helms J, Kremer S, Merdji H et al (2020) Neurologic features in severe SARS-CoV-2 infection. N Engl J Med 382(23):2268–2270. https://doi.org/10.1056/NEJMc2008597CrossRefPubMed

Heneka MT, Golenbock D, Latz E, Morgan D, Brown R (2020) Immediate and long-term consequences of COVID-19 infections for the development of neurological disease. Alzheimers Res Ther 12(1):69. https://doi.org/10.1186/s13195-020-00640-3CrossRefPubMedPubMedCentral

Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI (1990) Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Ann Intern Med 113(12):941–948. https://doi.org/10.7326/0003-4819-113-12-941CrossRefPubMed

Iwashyna TJ, Ely EW, Smith DM, Langa KM (2010) Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 304(16):1787–1794. https://doi.org/10.1001/jama.2010.1553CrossRefPubMedPubMedCentral

Kant IMJ, de Bresser J, van Montfort SJT, Slooter AJC, Hendrikse J (2017) MRI markers of neurodegenerative and neurovascular changes in relation to postoperative delirium and postoperative cognitive decline. Am J Geriatr Psychiatry 25(10):1048–1061. https://doi.org/10.1016/j.jagp.2017.06.016CrossRefPubMed

Kirschenbaum D, Imbach LL, Rushing EJ et al (2021) Intracerebral endotheliitis and microbleeds are neuropathological features of COVID-19. Neuropathol Appl Neurobiol 47(3):454–459. https://doi.org/10.1111/nan.12677CrossRefPubMed

Kluger MT, Skarin M, Collier J et al (2021) Steroids to reduce the impact on delirium (STRIDE): a double-blind, randomised, placebo-controlled feasibility trial of pre-operative dexamethasone in people with hip fracture. Anaesthesia 76(8):1031–1041. https://doi.org/10.1111/anae.15465CrossRefPubMed

Lau KK, Li L, Schulz U et al (2017) Total small vessel disease score and risk of recurrent stroke: validation in 2 large cohorts. Neurology 88(24):2260–2267. https://doi.org/10.1212/WNL.0000000000004042CrossRefPubMedPubMedCentral

Matsuda K, Shindo A, Ii Y et al (2021) Investigation of hypertensive arteriopathy-related and cerebral amyloid angiopathy-related small vessel disease scores in patients from a memory clinic: a prospective single-centre study. BMJ Open 11(4):e042550. https://doi.org/10.1136/bmjopen-2020-042550CrossRefPubMedCentral

Mendes A, Herrmann FR, Périvier S, Gold G, Graf CE, Zekry D (2021) Delirium in older patients with COVID-19: prevalence, risk factors, and clinical relevance. J Gerontol A Biol Sci Med Sci 76(8):e142–e146. https://doi.org/10.1093/gerona/glab039CrossRefPubMed

Paterson RW, Benjamin LA, Mehta PR et al (2021) Serum and cerebrospinal fluid biomarker profiles in acute SARS-CoV-2-associated neurological syndromes. Brain Commun. (Published online 2021:fcab099-fcab099)

Pensato U, Muccioli L, Cani I et al (2021) Brain dysfunction in COVID-19 and CAR-T therapy: cytokine storm-associated encephalopathy. Ann Clin Transl Neurol 8(4):968–979. https://doi.org/10.1002/acn3.51348CrossRefPubMedPubMedCentral

Pilotto A, Odolini S, Masciocchi S et al (2020) Steroid-responsive encephalitis in coronavirus disease 2019. Ann Neurol 88(2):423–427. https://doi.org/10.1002/ana.25783CrossRefPubMedPubMedCentral

Pizzato Tondo L, Beck Paglioli Neto E, Arpini S, Passos G, Becker J (2021) Encephalopathy due to COVID-19 with great response to glucocorticoids. Cureus. 13(9):e17845. https://doi.org/10.7759/cureus.17845CrossRefPubMedPubMedCentral

Pugin D, Vargas MI, Thieffry C et al (2020) COVID-19-related encephalopathy responsive to high-dose glucocorticoids. Neurology 95(12):543–546. https://doi.org/10.1212/WNL.0000000000010354CrossRefPubMed

Sessler CN, Gosnell MS, Grap MJ et al (2002) The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 166(10):1338–1344. https://doi.org/10.1164/rccm.2107138CrossRefPubMed

Uginet M, Breville G, Assal F et al (2021) COVID-19 encephalopathy: clinical and neurobiological features. J Med Virol 93(7):4374–4381. https://doi.org/10.1002/jmv.26973CrossRefPubMedPubMedCentral

Uginet M, Breville G, Hofmeister J et al (2022a) Cerebrovascular complications and vessel wall imaging in COVID-19 encephalopathy—a pilot study. Clin Neuroradiol 32(1):287–293. https://doi.org/10.1007/s00062-021-01008-2CrossRefPubMed

Uginet M, Breville G, Hofmeister J et al (2022b) Answer to letter to the editor: high-resolution black blood vessel wall imaging in COVID-19 encephalopathy-is it really endotheliitis? Clin Neuroradiol 32(1):297–298. https://doi.org/10.1007/s00062-021-01113-2CrossRefPubMed

Varga Z, Flammer AJ, Steiger P et al (2020) Endothelial cell infection and endotheliitis in COVID-19. Lancet 395(10234):1417–1418. https://doi.org/10.1016/S0140-6736(20)30937-5CrossRefPubMedPubMedCentral

Wilke V, Sulyok M, Stefanou MI et al (2022) Delirium in hospitalized COVID-19 patients: predictors and implications for patient outcome. PLoS One 17(12):e0278214. https://doi.org/10.1371/journal.pone.0278214CrossRefPubMedPubMedCentral

Xiang XB, Chen H, Wu YL, Wang K, Yue X, Cheng XQ (2022) The effect of preoperative methylprednisolone on postoperative delirium in older patients undergoing gastrointestinal surgery: a randomized, double-blind, placebo-controlled trial. J Gerontol A Biol Sci Med Sci 77(3):517–523. https://doi.org/10.1093/gerona/glab248CrossRefPubMed

Title: High-dose glucocorticoids in COVID-19 patients with acute encephalopathy: clinical and imaging findings in a retrospective cohort study
Authors: Alexandra Rhally
Giulia Bommarito
Marjolaine Uginet
Gautier Breville
Patrick Stancu
Alice Accorroni
Frédéric Assal
Patrice H. Lalive
Karl-Olof Lövblad
Gilles Allali
Publication date: 16-02-2024
Publisher: Springer Vienna
Keywords: Glucocorticoid
COVID-19
Encephalopathy
Cerebral Small Vessel Disease
Published in: Journal of Neural Transmission / Issue 4/2024
Print ISSN: 0300-9564
Electronic ISSN: 1435-1463
DOI: https://doi.org/10.1007/s00702-024-02751-9

At a glance: The STEP trials

Springer Medicine

High-dose glucocorticoids in COVID-19 patients with acute encephalopathy: clinical and imaging findings in a retrospective cohort study

Abstract

Objectives

Method

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Objectives

Method

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 4/2024

Association between autonomic dysfunction with motor and non-motor symptoms in patients with Parkinson's disease

Correlation between the MNCD classification-based staging of Parkinson’s disease and quality of life: a cross-sectional study

Mild cognitive impairment in Huntington’s disease: challenges and outlooks

Prof. DDr. Gregor K. Wenning (1964–2024)

Combined light and electron microscopy (CLEM) to quantify methamphetamine-induced alpha-synuclein-related pathology

More than fear? Brain activation patterns of dental phobic patients before and after an exposure-based treatment