open access

Vol 55, No 6 (2021)
Review Article
Submitted: 2021-05-27
Accepted: 2021-08-27
Published online: 2021-10-12
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Autoimmune mediated hyperkinetic movement disorders in SARS-CoV-2 infection — a systematic review

Adam S. Hirschfeld1
·
Pubmed: 34637137
·
Neurol Neurochir Pol 2021;55(6):549-558.
Affiliations
  1. University of Medical Sciences Chair and Department of Medical Genetics, Poznan, Poland

open access

Vol 55, No 6 (2021)
Review articles
Submitted: 2021-05-27
Accepted: 2021-08-27
Published online: 2021-10-12

Abstract

Introduction. Various neurological symptoms have been confirmed in the course of SARS-CoV-2 infection. Some of these are undoubtedly the aftermath of the developing inflammation and increased coagulation processes. However, there is also a group of symptoms that derive from possible autoimmune processes. These include primary hyperkinetic movement disorders such as myoclonus, ataxia, opsoclonus, and tremors. This study systematically reviews scientific reports presenting patients with hyperkinetic movement disorders as one of the neurological symptoms.

Material and methods. The available literature was systematically reviewed as per the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The PubMed database was used in the range from 1 April, 2020, to 31 July, 2021.

Results. The PubMed database search identified 102 cases of patients with SARS-CoV-2 infection who developed hyperkinetic movement disorders. After excluding patients undergoing mechanical ventilation (n = 46) and a few other cases (n = 7), a group of 49 non-intubated patients was obtained. The mean age of the patients was 57.92 years, and 75.51% of the patients were male. The most common hyperkinetic movement disorders were ataxia (83.67%), myoclonus (67.35%), and tremor (30.61%). Symptoms appeared on average within two weeks of the first symptoms of infection. Most patients had symptoms significantly
reduced or withdrawn (67.44%) or early partial improvement (30.23%).

Conclusions. Based on the meta-analysis, it can be concluded that hyperkinetic movement disorders in the course of SARS-CoV-2 infection are an early symptom with a potential autoimmune background. They have a good prognosis with the applied treatment. Further observations are needed to determine their frequency and the most effective methods of treatment.

Abstract

Introduction. Various neurological symptoms have been confirmed in the course of SARS-CoV-2 infection. Some of these are undoubtedly the aftermath of the developing inflammation and increased coagulation processes. However, there is also a group of symptoms that derive from possible autoimmune processes. These include primary hyperkinetic movement disorders such as myoclonus, ataxia, opsoclonus, and tremors. This study systematically reviews scientific reports presenting patients with hyperkinetic movement disorders as one of the neurological symptoms.

Material and methods. The available literature was systematically reviewed as per the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The PubMed database was used in the range from 1 April, 2020, to 31 July, 2021.

Results. The PubMed database search identified 102 cases of patients with SARS-CoV-2 infection who developed hyperkinetic movement disorders. After excluding patients undergoing mechanical ventilation (n = 46) and a few other cases (n = 7), a group of 49 non-intubated patients was obtained. The mean age of the patients was 57.92 years, and 75.51% of the patients were male. The most common hyperkinetic movement disorders were ataxia (83.67%), myoclonus (67.35%), and tremor (30.61%). Symptoms appeared on average within two weeks of the first symptoms of infection. Most patients had symptoms significantly
reduced or withdrawn (67.44%) or early partial improvement (30.23%).

Conclusions. Based on the meta-analysis, it can be concluded that hyperkinetic movement disorders in the course of SARS-CoV-2 infection are an early symptom with a potential autoimmune background. They have a good prognosis with the applied treatment. Further observations are needed to determine their frequency and the most effective methods of treatment.

Get Citation

Keywords

Covid, SARS-CoV-2, ataxia, myoclonus, autoimmune

About this article
Title

Autoimmune mediated hyperkinetic movement disorders in SARS-CoV-2 infection — a systematic review

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 55, No 6 (2021)

Article type

Review Article

Pages

549-558

Published online

2021-10-12

Page views

7061

Article views/downloads

926

DOI

10.5603/PJNNS.a2021.0069

Pubmed

34637137

Bibliographic record

Neurol Neurochir Pol 2021;55(6):549-558.

Keywords

Covid
SARS-CoV-2
ataxia
myoclonus
autoimmune

Authors

Adam S. Hirschfeld

References (94)
  1. Zhu H, Wei Li, Niu P. The novel coronavirus outbreak in Wuhan, China. Glob Health Res Policy. 2020; 5: 6.
  2. WHO Coronavirus (COVID-19) Dashboard. https://covid19.who.int (08/05/2021).
  3. Collantes ME, Espiritu AI, Sy MC, et al. Neurological manifestations in COVID-19 infection: A systematic review and meta-analysis. Can J Neurol Sci. 2021; 48(1): 66–76.
  4. Gao Z, Xu Y, Sun C, et al. A systematic review of asymptomatic infections with COVID-19. J Microbiol Immunol Infect. 2021; 54(1): 12–16.
  5. Lopez-Leon S, Wegman-Ostrosky T, Perelman C, et al. More than 50 Long-term effects of COVID-19: a systematic review and meta-analysis. medRxiv. 2021.
  6. Nuzzo D, Cambula G, Bacile I, et al. Long-term brain disorders in Post Covid-19 Neurological Syndrome (PCNS) patient. Brain Sci. 2021; 11(4).
  7. Maury A, Lyoubi A, Peiffer-Smadja N, et al. Neurological manifestations associated with SARS-CoV-2 and other coronaviruses: A narrative review for clinicians. Rev Neurol (Paris). 2021; 177(1-2): 51–64.
  8. Kacem I, Gharbi A, Harizi C, et al. Characteristics, onset, and evolution of neurological symptoms in patients with COVID-19. Neurol Sci. 2021; 42(1): 39–46.
  9. Martinez-Fierro ML, Diaz-Lozano M, Alvarez-Zuñiga C, et al. Population-based COVID-19 screening in Mexico: assessment of symptoms and their weighting in predicting SARS-CoV-2 infection. Medicina (Kaunas). 2021; 57(4).
  10. Armangué T, Sabater L, Torres-Vega E, et al. Clinical and immunological features of opsoclonus-myoclonus syndrome in the era of neuronal cell surface antibodies. JAMA Neurol. 2016; 73(4): 417–424.
  11. Mondal R, Deb S, Shome G, et al. COVID-19 and emerging spinal cord complications: A systematic review. Mult Scler Relat Disord. 2021; 51: 102917.
  12. Ashraf M, Sajed S. Acute stroke in a young patient with coronavirus disease 2019 in the presence of patent foramen ovale. Cureus. 2020; 12(9): e10233.
  13. Sartoretti E, Sartoretti T, Imoberdorf R, et al. Long-segment arterial cerebral vessel thrombosis after mild COVID-19. BMJ Case Rep. 2020; 13(9).
  14. Pezzini A, Padovani A. Lifting the mask on neurological manifestations of COVID-19. Nat Rev Neurol. 2020; 16(11): 636–644.
  15. Chan JL, Murphy KA, Sarna JR. Myoclonus and cerebellar ataxia associated with COVID-19: a case report and systematic review. J Neurol. 2021 [Epub ahead of print].
  16. Shamseer L, Moher D, Clarke M, et al. PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015: elaboration and explanation. BMJ. 2015; 350: g7647.
  17. Emamikhah M, Babadi M, Mehrabani M, et al. Opsoclonus-myoclonus syndrome, a post-infectious neurologic complication of COVID-19: case series and review of literature. J Neurovirol. 2021; 27(1): 26–34.
  18. Werner J, Reichen I, Huber M, et al. Subacute cerebellar ataxia following respiratory symptoms of COVID-19: a case report. BMC Infect Dis. 2021; 21(1): 298.
  19. Fernandes J, Puhlmann P. Opsoclonus myoclonus ataxia syndrome in severe acute respiratory syndrome coronavirus-2. J Neurovirol. 2021; 27(3): 501–503.
  20. Foucard C, San-Galli A, Tarrano C, et al. Acute cerebellar ataxia and myoclonus with or without opsoclonus: a parainfectious syndrome associated with COVID-19. Eur J Neurol. 2021 [Epub ahead of print].
  21. Schellekens MMI, Bleeker-Rovers CP, Keurlings PAJ, et al. Reversible myoclonus-ataxia as a postinfectious manifestation of COVID-19. Mov Disord Clin Pract. 2020; 7(8): 977–979.
  22. Urrea-Mendoza E, Okafor K, Ravindran S, et al. Opsoclonus-myoclonus-ataxia syndrome (OMAS) associated with SARS-CoV-2 infection: post-Infectious neurological complication with benign prognosis. Tremor Other Hyperkinet Mov (N Y). 2021; 11: 7.
  23. El Otmani H, Moutaouakil F, Ouazzani M, et al. Isolated generalized myoclonus immune-mediated by SARS-CoV-2: an illustrative videotaped case. Neurol Sci. 2021; 42(8): 3411–3413.
  24. Borroni B, Gazzina S, Dono F, et al. Diaphragmatic myoclonus due to SARS-CoV-2 infection. Neurol Sci. 2020; 41(12): 3471–3474.
  25. Grimaldi S, Lagarde S, Harlé JR, et al. Autoimmune encephalitis concomitant with SARS-CoV-2 infection: insight from F-FDG PET imaging and neuronal autoantibodies. J Nucl Med. 2020; 61(12): 1726–1729.
  26. Wright D, Rowley R, Halks-Wellstead P, et al. Abnormal saccadic oscillations associated with severe acute respiratory syndrome Coronavirus 2 encephalopathy and ataxia. Mov Disord Clin Pract. 2020; 7(8): 980–982.
  27. Anand P, Zakaria A, Benameur K, et al. Myoclonus in patients with coronavirus disease 2019: a multicenter case series. Crit Care Med. 2020; 48(11): 1664–1669.
  28. Delorme C, Paccoud O, Kas A, et al. CoCo-Neurosciences study group and COVID SMIT PSL study group. COVID-19-related encephalopathy: a case series with brain FDG-positron-emission tomography/computed tomography findings. Eur J Neurol. 2020; 27(12): 2651–2657.
  29. Dijkstra F, Van den Bossche T, Willekens B, et al. Myoclonus and cerebellar ataxia following Coronavirus Disease 2019 (COVID-19). Mov Disord Clin Pract. 2020 [Epub ahead of print].
  30. Sanguinetti SY, Ramdhani RA. Opsoclonus-myoclonus-ataxia syndrome related to the novel coronavirus (COVID-19). J Neuroophthalmol. 2021; 41(3): e288–e289.
  31. Khoo A, McLoughlin B, Cheema S, et al. Postinfectious brainstem encephalitis associated with SARS-CoV-2. J Neurol Neurosurg Psychiatry. 2020; 91(9): 1013–1014.
  32. Balestrino R, Rizzone M, Zibetti M, et al. Onset of Covid-19 with impaired consciousness and ataxia: a case report. J Neurol. 2020; 267(10): 2797–2798.
  33. Diezma-Martín AM, Morales-Casado MI, García-Alvarado N, et al. [Tremor and ataxia in COVID-19]. Neurologia (Engl Ed). 2020; 35(6): 409–410.
  34. Rábano-Suárez P, Bermejo-Guerrero L, Méndez-Guerrero A, et al. Generalized myoclonus in COVID-19. Neurology. 2020; 95(6): e767–e772.
  35. Manganotti P, Pesavento V, Buoite Stella A, et al. Miller Fisher syndrome diagnosis and treatment in a patient with SARS-CoV-2. J Neurovirol. 2020; 26(4): 605–606.
  36. Manganotti P, Bellavita G, D'Acunto L, et al. Clinical neurophysiology and cerebrospinal liquor analysis to detect Guillain-Barré syndrome and polyneuritis cranialis in COVID-19 patients: A case series. J Med Virol. 2021; 93(2): 766–774.
  37. Lantos JE, Strauss SB, Lin E. COVID-19-associated Miller Fisher syndrome: MRI findings. AJNR Am J Neuroradiol. 2020; 41(7): 1184–1186.
  38. Fadakar N, Ghaemmaghami S, Masoompour SM, et al. A first case of acute cerebellitis associated with coronavirus disease (COVID-19): a case report and literature review. Cerebellum. 2020; 19(6): 911–914.
  39. Kopscik MR, Giourgas BK, Presley BC. A case report of acute motor and sensory polyneuropathy as the presenting symptom of SARS-CoV-2. Clin Pract Cases Emerg Med. 2020; 4(3): 352–354.
  40. Perrin P, Collongues N, Baloglu S, et al. Cytokine release syndrome-associated encephalopathy in patients with COVID-19. Eur J Neurol. 2021; 28(1): 248–258.
  41. Povlow A, Auerbach AJ. Acute cerebellar ataxia in COVID-19 infection: A case report. J Emerg Med. 2021; 60(1): 73–76.
  42. Gutiérrez-Ortiz C, Méndez-Guerrero A, Rodrigo-Rey S, et al. Miller Fisher syndrome and polyneuritis cranialis in COVID-19. Neurology. 2020; 95(5): e601–e605.
  43. Fernández-Domínguez J, Ameijide-Sanluis E, García-Cabo C, et al. Miller-Fisher-like syndrome related to SARS-CoV-2 infection (COVID 19). J Neurol. 2020; 267(9): 2495–2496.
  44. Fernando EZ, Yu JR, Santos SM, et al. Involuntary movements following administration of hydroxychloroquine for COVID-19 pneumonia. J Mov Disord. 2021; 14(1): 75–77.
  45. Shetty K, Jadhav AM, Jayanthakumar R, et al. Myoclonus-ataxia syndrome associated with COVID-19. J Mov Disord. 2021; 14(2): 153–156.
  46. Blanco-Palmero VA, Azcárate-Díaz FJ, Ruiz-Ortiz M, et al. Serum and CSF alpha-synuclein levels do not change in COVID-19 patients with neurological symptoms. J Neurol. 2021; 268(9): 3116–3124.
  47. Giannantoni NM, Rigamonti E, Rampolli FI, et al. Myoclonus and cerebellar ataxia associated with SARS-CoV-2 infection: case report and review of the literature. Eur J Case Rep Intern Med. 2021; 8(5): 002531.
  48. Przytuła F, Błądek S, Sławek J. Two COVID-19-related video-accompanied cases of severe ataxia-myoclonus syndrome. Neurol Neurochir Pol. 2021; 55(3): 310–313.
  49. Saha B, Saha S, Chong WH. 78-year-old woman with opsoclonus myoclonus ataxia syndrome secondary to COVID-19. BMJ Case Rep. 2021; 14(5).
  50. Ishaq H, Durrani T, Umar Z, et al. Post-COVID opsoclonus myoclonus syndrome: A case report from Pakistan. Front Neurol. 2021; 12: 672524.
  51. Emekli AS, Parlak A, Göcen NY, et al. Anti-GAD associated post-infectious cerebellitis after COVID-19 infection. Neurol Sci. 2021 [Epub ahead of print].
  52. Grieb A, Seitz T, Kitzberger R, et al. COVID-19-associated myoclonus in a series of five critically ill patients. Wien Klin Wochenschr. 2021 [Epub ahead of print].
  53. Ruggeri RM, Campennì A, Siracusa M, et al. Subacute thyroiditis in a patient infected with SARS-COV-2: an endocrine complication linked to the COVID-19 pandemic. Hormones (Athens). 2021; 20(1): 219–221.
  54. Park JE, Kwon KY. Coronavirus disease 2019-associated worsening and improvement of ataxia and gait in a patient with multiple system atrophy. Geriatr Gerontol Int. 2021; 21(7): 591–593.
  55. Muccioli L, Rondelli F, Ferri L, et al. Subcortical myoclonus in COVID-19: comprehensive evaluation of a patient. Mov Disord Clin Pract. 2020 [Epub ahead of print].
  56. Chaumont H, San-Galli A, Martino F, et al. Mixed central and peripheral nervous system disorders in severe SARS-CoV-2 infection. J Neurol. 2020; 267(11): 3121–3127.
  57. Cuhna P, Herlin B, Vassilev K, et al. Movement disorders as a new neurological clinical picture in severe SARS-CoV-2 infection. Eur J Neurol. 2020; 27(12): e88–e90.
  58. Méndez-Guerrero A, Laespada-García MI, Gómez-Grande A, et al. Acute hypokinetic-rigid syndrome following SARS-CoV-2 infection. Neurology. 2020; 95(15): e2109–e2118.
  59. Lowery MM, Taimur Malik M, Seemiller J, et al. Atypical variant of guillain Barre syndrome in a patient with COVID-19. J Crit Care Med (Targu Mures). 2020; 6(4): 231–236.
  60. Ros-Castelló V, Quereda C, López-Sendón J, et al. Post-hypoxic myoclonus after COVID-19 infection recovery. Mov Disord Clin Pract. 2020 [Epub ahead of print].
  61. Franke C, Ferse C, Kreye J, et al. High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms. Brain Behav Immun. 2021; 93: 415–419.
  62. Hayashi M, Sahashi Y, Baba Y, et al. COVID-19-associated mild encephalitis/encephalopathy with a reversible splenial lesion. J Neurol Sci. 2020; 415: 116941.
  63. Lahiri D, Ardila A. COVID-19 pandemic: A neurological perspective. Cureus. 2020; 12(4): e7889.
  64. Clark JR, Liotta EM, Reish NJ, et al. Abnormal movements in hospitalized COVID-19 patients: A case series. J Neurol Sci. 2021; 423: 117377.
  65. Mao L, Jin H, Wang M, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 2020; 77(6): 683–690.
  66. Mahammedi A, Saba L, Vagal A, et al. Imaging of neurologic disease in hospitalized patients with COVID-19: an Italian multicenter retrospective observational study. Radiology. 2020; 297(2): E270–E273.
  67. Agarwal P, Ray S, Madan A, et al. Neurological manifestations in 404 COVID-19 patients in Washington State. J Neurol. 2021; 268(3): 770–772.
  68. Mitoma H, Adhikari K, Aeschlimann D, et al. Consensus Paper: Neuroimmune mechanisms of cerebellar ataxias. Cerebellum. 2016; 15(2): 213–232.
  69. Ganos C, Kassavetis P, Erro R, et al. The role of the cerebellum in the pathogenesis of cortical myoclonus. Mov Disord. 2014; 29(4): 437–443.
  70. Rozenberg S, Vandromme J, Martin C. Are we equal in adversity? Does Covid-19 affect women and men differently? Maturitas. 2020; 138: 62–68.
  71. Jin JM, Bai P, He W, et al. Gender differences in patients with COVID-19: focus on severity and mortality. Front Public Health. 2020; 8: 152.
  72. Moulton VR. Sex hormones in acquired immunity and autoimmune disease. Front Immunol. 2018; 9: 2279.
  73. Lechien JR, Chiesa-Estomba CM, De Siati DR, et al. Olfactory and gustatory dysfunctions as a clinical presentation of mild-to-moderate forms of the coronavirus disease (COVID-19): a multicenter European study. Eur Arch Otorhinolaryngol. 2020; 277(8): 2251–2261.
  74. Husain Q, Kokinakos K, Kuo YH, et al. Characteristics of COVID-19 smell and taste dysfunction in hospitalized patients. Am J Otolaryngol. 2021 [Epub ahead of print]; 42(6): 103068.
  75. Bagheri S, Asghari A, Farhadi M, et al. Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak in Iran. Medical Journal of The Islamic Republic of Iran. 2020; 34.
  76. Choi Y, Lee MK. Neuroimaging findings of brain MRI and CT in patients with COVID-19: A systematic review and meta-analysis. Eur J Radiol. 2020; 133: 109393.
  77. Chougar L, Shor N, Weiss N, et al. CoCo Neurosciences Study Group. Retrospective observational study of brain MRI findings in patients with acute SARS-CoV-2 infection and neurologic manifestations. Radiology. 2020; 297(3): E313–E323.
  78. Connolly A, Pestronk A, Mehta S, et al. Serum autoantibodies in childhood opsoclonus-myoclonus syndrome: An analysis of antigenic targets in neural tissues. The Journal of Pediatrics. 1997; 130(6): 878–884.
  79. Grimaldi S, Lagarde S, Harlé JR, et al. Autoimmune encephalitis concomitant with SARS-CoV-2 infection: insight from F-FDG PET imaging and neuronal autoantibodies. J Nucl Med. 2020; 61(12): 1726–1729.
  80. Baig AM, Khaleeq A, Ali U, et al. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci. 2020; 11(7): 995–998.
  81. Mehta P, McAuley D, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. The Lancet. 2020; 395(10229): 1033–1034.
  82. Gold DM, Galetta SL. Neuro-ophthalmologic complications of coronavirus disease 2019 (COVID-19). Neurosci Lett. 2021; 742: 135531.
  83. Matschke J, Lütgehetmann M, Hagel C, et al. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. The Lancet Neurology. 2020; 19(11): 919–929.
  84. Netravathi M, Pal PK, Indira Devi B. A clinical profile of 103 patients with secondary movement disorders: correlation of etiology with phenomenology. Eur J Neurol. 2012; 19(2): 226–233.
  85. Victorino DB, Guimarães-Marques M, Nejm M, et al. COVID-19 and stroke: Red flags for secondary movement disorders? eNeurologicalSci. 2020; 21: 100289.
  86. Follmer C. Gut microbiome imbalance and neuroinflammation: impact of COVID-19 on Parkinson's disease. Mov Disord. 2020; 35(9): 1495–1496.
  87. Hashimoto T, Perlot T, Rehman A, et al. ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature. 2012; 487(7408): 477–481.
  88. Romano S, Savva GM, Bedarf JR, et al. Meta-analysis of the Parkinson's disease gut microbiome suggests alterations linked to intestinal inflammation. NPJ Parkinsons Dis. 2021; 7(1): 27.
  89. Labandeira-Garcia JL, Rodriguez-Pallares J, Dominguez-Meijide A, et al. Dopamine-angiotensin interactions in the basal ganglia and their relevance for Parkinson's disease. Mov Disord. 2013; 28(10): 1337–1342.
  90. Boika AV. A Post-COVID-19 Parkinsonism in the future? Mov Disord. 2020; 35(7): 1094.
  91. Hao F, Tan W, Jiang Li, et al. Do psychiatric patients experience more psychiatric symptoms during COVID-19 pandemic and lockdown? A case-control study with service and research implications for immunopsychiatry. Brain Behav Immun. 2020; 87: 100–106.
  92. Piscitelli D, Perin C, Tremolizzo L, et al. Functional movement disorders in a patient with COVID-19. Neurol Sci. 2020; 41(9): 2343–2344.
  93. Gupta H, Caviness J. Post-hypoxic myoclonus: current concepts, neurophysiology, and treatment. Tremor and Other Hyperkinetic Movements. 2016; 6(0): 409.
  94. Moningi S, Reddy GP, Nikhar SA, et al. Comparison of the influence of low dose etomidate and propofol as priming dose on the incidence of etomidate induced myoclonus: a randomised, double-blind clinical trial. Braz J Anesthesiol. 2021 [Epub ahead of print].

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