Skip Navigation
Skip to contents

JMD : Journal of Movement Disorders

OPEN ACCESS
SEARCH
Search

Articles

Page Path
HOME > J Mov Disord > Early view > Article
Brief communication
COVID-19 Vaccine-Related Movement Disorders: A Systematic Review
Grace Elysse D. Angeles1orcid, Lowrence Precious C. Dichoso1orcid, Roland Dominic G. Jamora1,2corresp_iconorcid
> Epub ahead of print
DOI: https://doi.org/10.14802/jmd.24001
Published online: March 19, 2024

1Division of Adult Neurology, Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Manila, Philippines

2Section of Neurology, Department of Internal Medicine, Cardinal Santos Medical Center, San Juan City, Philippines

Corresponding author: Roland Dominic G. Jamora, MD, PhD Division of Adult Neurology, Department of Neurosciences, College of Medicine and Philippine General Hospital, University of the Philippines Manila, Zone 72, 670 Padre Faura St, Ermita, Manila 1000, Philippines / Tel: +62-385548400 / E-mail: rgjamora@up.edu.ph
• Received: January 2, 2024   • Revised: February 12, 2024   • Accepted: March 18, 2024

Copyright © 2024 The Korean Movement Disorder Society

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

  • 1,141 Views
  • 79 Download
  • Objective
    Since the release of vaccines against coronavirus disease 2019 (COVID-19), there have been reports of vaccine-related neurologic complications. This study aimed to perform a descriptive systematic review of movement disorders associated with COVID-19 vaccines.
  • Methods
    We described the demographics, clinical presentation, management, outcomes, and proposed pathomechanism of the patients. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A standardized tool was used to assess the quality of the cases.
  • Results
    We identified 8 articles that met our inclusion criteria; these articles included 10 patients who developed movement disorders after vaccination. The majority were males (n = 8), with a median age of 64.5 years. The most common movement disorder was hemichorea. The rest presented with generalized chorea with myoclonus, cervical dystonia, and akathisia. Most patients respond to immunotherapy. The standardized tool used showed that most studies had a low risk of bias.
  • Conclusion
    The reported incidence of vaccine-related movement disorders was low based on available published cases.
Severe acute respiratory syndrome coronavirus-2, the strain that causes coronavirus disease 2019 (COVID-19), primarily affects the respiratory system and led to the declaration of a global pandemic in March 2020 [1]. The development of vaccines against this novel virus was expedited to prevent further spread of the disease. As of August 2023, 12 vaccines have been granted emergency use listing by the World Health Organization (WHO), and more than 13.1 billion vaccines have been administered worldwide (https://extranet.who.int/prequal/vaccines/covid-19-vaccines-who-emergency-use-listing) [2]. The documentation of rare adverse events makes it important for risk-benefit evaluations due to the lack of available clinical trials [3]. Notably, neurological complications following COVID-19, such as movement disorders, have been reported in case reports with a frequency of 0.00002–0.0002 [4].
Several studies have reported movement disorders associated with ongoing or previous COVID-19 infection. However, few studies have investigated COVID-19 vaccine-related movement disorders. Despite the large databases that were established to detect adverse effects of the COVID-19 vaccine, detailed documentation on the identified movement disorders was not included.
While case reports may be limited by their ability to establish generalizations, they provide a more comprehensive investigation to confirm that movement disorders are more likely to result from COVID-19 vaccination. A systematic review of case reports may have a significant role in documenting the clinical presentation, ancillary tests performed, neuroimaging, management and outcome to establish that the movement disorder was indeed vaccine related. This review aimed to provide thorough insight into the literature on movement disorders following COVID-19 vaccination.
This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The study was registered in the PROSPERO database of systematic reviews (PROSPERO registration number: CRD42023463797).
The researchers considered case series and case reports that included patients who developed movement disorders following any COVID-19 vaccine. We included all possible movement disorders, including hyperkinetic and hypokinetic movement disorders.
We included only case reports with detailed descriptions of the neurologic symptoms, vaccine received, symptom onset, cranial imaging, management, outcome and possible mechanism of vaccine-related adverse events. There were no restrictions in terms of age, sex or ethnicity of the population. We excluded studies that included patients with prior or ongoing COVID-19 infection, preexisting movement disorders, a history of neurodegenerative disease, functional neurologic disorder or encephalitis who developed abnormal movements during the course of illness.
We systematically searched for case reports and case series in the PubMed, EBSCO, Scopus, and WHO COVID-19 Research databases. We used the following general and MeSH terms: [“Movement disorders” OR “hyperkinetic” OR “hypokinetic” OR “dyskinesia” OR “myoclonus” OR “chorea” OR tremor” OR “tics” OR “ballism” OR “athetosis” OR “Parkinson’s disease” OR “Parkinsonism” OR “akathisia” OR “restless leg syndrome” OR “stiff person syndrome”] AND [“COVID-19 vaccine” OR “COMIRNATY BioNTech” OR “VAXZEVRIA AstraZeneca” OR “COVISHIELD ChAdOx1-S” OR “SPIKEVAX Moderna Biotech” OR “Inactivated COVID-19 Vaccine” OR “CoronaVac Sinovac” OR “COVAXIN” OR “COVOVAX” OR “NUVAXOVID” OR “CONVIDECIA” OR “SKYCovione (GBP510)”]. The literature search was limited to studies published from the inception of records in these major databases until July 2023.
Studies were identified through database searching and manual searching, and those that did not meet the inclusion criteria were excluded. The following data were extracted: patient demographics, descriptions of the movement disorder, vaccine received, symptom onset, cranial imaging, management, outcome and possible mechanism of vaccine-related adverse events.
Case reports and case series have a high likelihood of bias. To address this issue, the researchers adapted a standardized tool to assess quality according to four domains: selection, ascertainment, causality, and reporting (Supplementary Table 1 in the online-only Data Supplement) [5]. The sum of the scores is aggregated and classified as low, moderate, and high risk.
A PRISMA flow diagram of the selected studies is presented in Figure 1. A total of 363 studies were identified, 32 duplicates were removed, and 301 studies were excluded.
Eight articles contained 10 individual patients who met the inclusion criteria; 8 were male, and the median age was 64.5 years. Five of the patients did not report any comorbid medical conditions. Four individuals received the Pfizer BioNTech COVID-19 vaccine, two received the AZD1222 vaccine, two received the BBIBP-CorV (Sinopharm) vaccine, and the remaining received the ChAdOx1 nCoV-19 vaccine (n = 1) and Moderna Biotech (n = 1). Three patients experienced movement disorders after receiving their second dose of vaccine, and the remaining patients (n = 7) experienced symptoms after receiving their first dose. Symptoms presented as early as 12 hours, and the latest symptoms were reported after 40 days of vaccination. The majority (n = 7) reported hemichorea as the predominant movement disorder after receiving the COVID-19 vaccine (Table 1) [6-13]. The remaining patients reported generalized chorea with myoclonus, cervical dystonia, akathisia, and hemiballismus. Cranial imaging was mostly unremarkable for the cases reported. One of the reported cases involved vaccine-induced thrombocytopenia resulting in an ischemic infarct in the thalamus [6]. Another case reported the presence of voltage-gated potassium channel and glutamic acid decarboxylase serum antibodies, possibly explaining an autoimmune-mediated movement disorder [7].
The possibility of an autoimmune post-vaccination reaction was the proposed pathophysiology for vaccine-related movement disorders. Methylprednisolone and intravenous immunoglobulin therapy showed promising results in seven of the cases reported. In one case report, tetrabenazine was used but was eventually discontinued due to the absence of any effect, after which the patient was switched to methylprednisolone therapy [8]. Other therapeutic options that have been used include clonazepam and botulinum toxin for the treatment of dystonia and hemichorea, haloperidol for hemichorea, and ropinirole for generalized chorea. Another patient reported vaccine-induced prothrombotic immune thrombocytopenia based on cranial imaging and hence was given anticoagulants [6].
The researchers used a standardized tool to assess the methodological quality of the studies (Supplementary Table 1 in the online-only Data Supplement) [5]. One case report was determined to have a high risk of bias and did not include any neuroimaging results or other ancillary tests to rule out other differential diagnoses.
Over 13.5 billion vaccines have been administered by 2023; however, there is a lack of documentation on COVID-19 vaccine-related movement disorders [2]. After a thorough search, this review identified 10 cases of vaccine-related movement disorders. The majority of the patients were males, with a median age of 64.5 years, who received their first dose of the COVID-19 vaccine. In the studies reviewed, hemichorea was the most common movement disorder, and autoimmunity was the proposed pathomechanism.
Hemichorea was the predominant movement disorder described as slow, irregular, and purposeless involuntary movements of the arms and legs [13]. According to a pharmacovigilance database, approximately 40 cases of hemichorea and hemiballismus have been attributed to COVID-19 vaccination; however, the details of these cases are unknown [8]. This study also revealed generalized chorea with myoclonus, cervical dystonia, and akathisia after COVID-19 vaccination. These movement disorders have also been reported in pharmacovigilance reports; however, there are no details on the associated workup, treatment or outcome [4].
Although cranial imaging has a role in the diagnosis of patients with movement disorders, cranial magnetic resonance imaging (MRI) was unremarkable in almost all of the patients who presented. Nonetheless, one patient showed abnormalities in functional imaging, showing perfusion pattern asymmetry on brain single photon emission computed tomography, hence detecting early changes in the uptake of tracers in the early clinical stages of disease [13]. In another case, a vaccine-induced prothrombotic thrombocytopenia showed ischemia on cranial MRI strategically located on the thalamus [6].
With the lack of clear identifiable laboratory evidence pointing to a different etiology and the universal response to immunotherapy, an autoimmune cause was the proposed pathomechanism in the identified case reports. An abnormal immunological attack resulting in neuronal dysfunction and manifesting as a movement disorder could be one of the most plausible causes of vaccine-induced movement disorders, similar to adult-onset autoimmune chorea and hemichorea [14,15]. Moreover, in addition to the COVID-19 vaccine, one patient reported acute chorea following vaccination against human papilloma virus due to molecular mimicry [16]. This autoimmune theory was also proposed for patients who had hyperkinetic disorders after having COVID-19 [17].
There were very few patients with vaccine-related movement disorders other than those caused by the COVID-19 vaccine. A literature search revealed one 30-year-old woman with postvaccine-related opsoclonus-myoclonus syndrome after rubella vaccination. The proposed pathomechanism was due to molecular mimicry resulting from the cross-reactivity of cerebral antigens and viral antigens [18]. In addition, postvaccine parkinsonism was documented after receiving anti-measles and antitetanus vaccines [4].
In future studies, patients with well-established functional neurologic disorders with movement disorder manifestations and patients with encephalitis as an adverse event of COVID-19 vaccination with a clinical presentation of abnormal movement may be included.
Conclusion
Movement disorders as a complication of COVID-19 vaccination are rare. In this systematic review, hemichorea was identified as the most common movement disorder after vaccination. This descriptive systematic review highlighted the autoimmune pathomechanism involved in the development of movement disorders, and treatment with immunotherapy resolved symptoms.
The online-only Data Supplement is available with this article at https://doi.org/10.14802/jmd.24001.
Supplementary Table 1.
Summary of quality assessment based on standardized tool by Murad et al [5]. (2018)
jmd-24001-Supplementary-Table-1.pdf

Conflicts of Interest

The authors have no financial conflicts of interest.

Funding Statement

None

Author Contributions

Conceptualization: Grace Elysse D. Angeles, Roland Dominic G. Jamora. Data curation: all authors. Formal analysis: Grace Elysse D. Angeles, Lowrence Precious C. Dichoso. Investigation: Grace Elysse D. Angeles, Lowrence Precious C. Dichoso. Methodology: Grace Elysse D. Angeles, Roland Dominic G. Jamora. Supervision: Roland Dominic G. Jamora. Validation: all authors. Visualization: Grace Elysse D. Angeles. Writing—original draft: Grace Elysse D. Angeles, Roland Dominic G. Jamora. Writing—review & editing: Grace Elysse D. Angeles, Roland Dominic G. Jamora.

None
Figure 1.
PRISMA flow diagram of included studies. WHO, World Health Organization; COVID, coronavirus disease; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.
jmd-24001f1.jpg
Table 1.
Clinical features of patients with COVID-19 vaccine related movement disorders
Study Movement disorder Age (yr)/sex Comorbidities Vaccine Symptom onset since vaccination Neuroimaging Management Outcome Proposed Pathophysiology
Shahali et al., [6] 2022 Right sided hemichorea 72/M None First dose ChAdOx1 nCoV-19 vaccine 9 days Cranial MRI: left thalamic ischemic infarct Nadroparin 90 U/kg/day sodium ozagrel 160 mg/day edaravone 60 mg/day methylprednisolone 1 g/kg haloperidol 0.75 mg/day warfarin 0.125 mg/kg/day Improved after 2 weeks Vaccine-induced prothrombotic immune thrombocytopenia
Dulanto et al., [7] 2023 Generalized chorea with myoclonus 57/F Type 2 diabetes mellitus, hypertension, dyslipidemia, gastritis, major depressive disorder, generalized anxiety disorder, and chronic substance abuse Second moderna booster 14 days Cranial MRI: unremarkable Methylprednisolone plasmapheresis rituximab 375 mg/m2 ropinirole (dose not specified) Chorea and myoclonus improved after immunotherapy Positive for voltage- gated potassium channel and glutamic acid decarboxylase antibodies pointing toward possible autoimmunity and molecular mimicry
Batot et al., [8] 2022 Left hemichorea-hemiballismus 90/M Hypertension, atrial fibrillation, prior myocardial infarction Second dose of the Pfizer-BioNTech Within hours after second dose, 21 days after first dose Cranial MRI: no abnormal signals in the basal ganglia Tetrabenzine 75 mg daily × 3 weeks Abnormal movements significantly improved 10 days after methylprednisolone with resolution of asymmetric metabolism of the putamen on FDG- PET Dysimmune reaction induced by COVID-19 vaccination
Olanzapine 7.5 mg daily for 1 week
FDG-PET: increased metabolism of right putamen (compared to the left) Methylprednisolone 1 g per day for 5 days
Algahtani et al., [9] 2022 Cervical dystonia with left laterocollis 38/M None First dose Pfizer-BioNTech BNT16B2b2 24 hours Cranial and cervical spine MRI: unremarkable Oral clonazepam 0.5 mg/day botulinum toxin (dose not specified) Responded transiently to medical therapy Autoantibody-mediated immunological dysfunction
Salinas and Dieppa, [10] 2021 Akathisia 36/F Atopic dermatitis, allergic rhinitis, anxiety Second dose Pfizer-BioNTech vaccine 12 hours None Spontaneously resolved Spontaneously resolved Extrapyramidal system involvement and immune response of triggered by vaccine
Matar et al., [11] 2021 Left hemichorea-hemiballismus 88/M Dyslipidemia, hypertension, gout First dose of AZD1222 16 days Cranial MRI: unremarkable Intravenous methylprednisolone 1 g for 3 doses Significant resolution within 24 hrs of first dose of methylprednisolone Autoimmune postvaccination reaction
Matar et al., [11] 2021 Left hemichorea-hemiballismus 84/M Asthma, allergic aspergillosis, primary orthostatic hypertension, treated colorectal, esophageal and prostate carcinoma First dose of AZD1222 40 days Cranial MRI: unremarkable Intravenous methylprednisolone 1 g for 3 doses Partial resolution after first dose of methylprednisolone, but resolved after 3 days of corticosteroids Autoimmune postvaccination reaction
Salari and Etemadifar, [12] 2022 Right sided hemichorea 13/M None First dose of BBIBP-CorV (Sinopharm) inactivated virus 7 days Cranial MRI: nonspecific multiple white matter lesions Intravenous methylprednisolone 1 g/d for 3 days followed by oral prednisolone 50 mg/d and tetrabenazine 25 mg/d Improved after 1 month follow-up Post vaccination inflammatory mechanism also seen on as white matter changes on MRI
Salari and Etemadifar, [12] 2022 Left sided hemichorea 18/M None BBIBP-CorV (Sinopharm) inactivated virus 7 days Cranial MRI: nonspecific white matter lesions Intravenous methylprednisolone 1 g/d for 3 days followed by oral prednisolone 50 mg/d, and tetrabenazine 25 mg/d Mild choreic movements after 1 month follow-up Post vaccination inflammatory mechanism
Ryu et al., [13] 2022 Right sided hemichorea 83/M None Second dose of Pfizer-BioNTech COVID-19 vaccine 1 day Cranial MRI: unremarkable Haloperidol 0.75 mg two times a day Relieved symptoms at two weeks of follow-up Unclear pathophysiology
Brain SPECT: perfusion pattern asymmetrically decreased in left thalamus

COVID-19, coronavirus disease 2019; SPECT, single photon emission tomography; MRI, magnetic resonance imaging; FDG-PET, fluorodeoxyglucose-positron emission tomography.

  • 1. Feng W, Zong W, Wang F, Ju S. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a review. Mol Cancer 2020;19:100.ArticlePubMedPMCPDF
  • 2. World Health Organization. Update on global COVID-19 vaccination [Internet]. Geneva: World Health Organization; 2023 [accessed on 2023 Sep 27]. Available at: https://apps.who.int/gb/COVID-19/pdf_files/2023/05_01/Item1.pdf.
  • 3. Patone M, Handunnetthi L, Saatci D, Pan J, Katikireddi SV, Razvi S, et al. Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection. Nat Med 2021;27:2144–2153.ArticlePubMedPMCPDF
  • 4. Schneider SA, Hennig A, Martino D. Relationship between COVID-19 and movement disorders: a narrative review. Eur J Neurol 2022;29:1243–1253.ArticlePubMedPDF
  • 5. Murad MH, Sultan S, Haffar S, Bazerbachi F. Methodological quality and synthesis of case series and case reports. BMJ Evid Based Med 2018;23:60–63.ArticlePubMedPMC
  • 6. Shahali H, Farahani RH, Asgari A, Hazrati E. Thalamic hemi-chorea: a rare complication after receiving the adenoviral vector-based COVID-19 vaccine: a case report. Clin Exp Vaccine Res 2022;11:217–221.ArticlePubMedPMCPDF
  • 7. Dulanto J, Chu D, Saffari P, Abdelshahid M, Xu P, Hauser J, et al. Three patients with chorea and positive voltage-gated potassium channel antibody: is this the link between hyperkinetic von Economo disease and COVID-19? Cureus 2023;15:e35666.ArticlePubMedPMC
  • 8. Batot C, Chea M, Zeidan S, Mongin M, Pop G, Mazoyer J, et al. Clinical and radiological follow-up of a Pfizer-BioNTech COVID-19 vaccine-induced hemichorea-hemiballismus. Tremor Other Hyperkinet Mov (N Y) 2022;12:16.ArticlePubMedPMC
  • 9. Algahtani HA, Shirah BH, Alwafi E. Acute cervical dystonia following the BNT162b2 mRNA COVID-19 vaccine. Clin Neurol Neurosurg 2022;218:107304.ArticlePubMedPMC
  • 10. Salinas MR, Dieppa M. Transient akathisia after the SARS-Cov-2 vaccine. Clin Park Relat Disord 2021;4:100098.ArticlePubMedPMC
  • 11. Matar E, Manser D, Spies JM, Worthington JM, Parratt KL. Acute hemichorea-hemiballismus following COVID-19 (AZD1222) vaccination. Mov Disord 2021;36:2714–2715.PubMedPMC
  • 12. Salari M, Etemadifar M. Two cousins with acute hemichorea after BBIBPCorV (Sinopharm) COVID-19 vaccine. Mov Disord 2022;37:1101–1103.PubMedPMC
  • 13. Ryu DW, Lim EY, Cho AH. A case of hemichorea following administration of the Pfizer-BioNTech COVID-19 vaccine. Neurol Sci 2022;43:771–773.ArticlePubMedPMCPDF
  • 14. Kyle K, Bordelon Y, Venna N, Linnoila J. Autoimmune and paraneoplastic chorea: a review of the literature. Front Neurol 2022;13:829076.ArticlePubMedPMC
  • 15. O’Toole O, Lennon VA, Ahlskog JE, Matsumoto JY, Pittock SJ, Bower J, et al. Autoimmune chorea in adults. Neurology 2013;80:1133–1144.ArticlePubMedPMC
  • 16. Decio A, Balottin U, De Giorgis V, Veggiotti P. Acute chorea in a child receiving second dose of human papilloma virus vaccine. Pediatr Allergy Immunol 2014;25:295–296.ArticlePubMed
  • 17. Hirschfeld AS. Autoimmune mediated hyperkinetic movement disorders in SARS-CoV-2 infection - a systematic review. Neurol Neurochir Pol 2021;55:549–558.ArticlePubMed
  • 18. Lapenna F, Lochi L, de Mari M, Iliceto G, Lamberti P. Post-vaccinic opsoclonus-myoclonus syndrome: a case report. Parkinsonism Relat Disord 2000;6:241–242.ArticlePubMed

Figure & Data

References

    Citations

    Citations to this article as recorded by  

      Comments on this article

      Roland Dominic Go Jamora

      We thank the authors for their comments. Due to the nature of our paper (systematic review of COVID-19 vaccine related movement disorders), we looked at the published articles available. The authors's issues on the small number of instances/ patients and the absence of specific information on the administered vaccine is again inherent to the available and limited number of publications (hence the systematic review). we are working with the data available in the published reports. The total number of vaccines administered worldwide and the limited number of published reports on vaccine related movement disorder might give us an idea as to its prevalence (while acknowledging the fact that not all events are published).

      June 04, 2024

      hinpetch daungsupawong

      COVID-19 vaccine related movement disorders: Comment
      Hinpetch Daungsupawong 1; Viroj Wiwanitkit2

      1.Private Academic Consultant, Phonhong, Lao People's Democratic Republic.
      2. 2.Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences Saveetha University India.


      Dear Editor, we would like to share ideas on the publication “COVID-19 vaccine related movement disorders: a systematic review.” In essence, the purpose of this study was to look into cases of movement difficulties after vaccination. The researchers found ten patients from eight articles who had mobility abnormalities following vaccination. The majority of patients were male, with a median age of 64.5 years. The most prevalent movement problem found was hemichorea, followed by generalized chorea with myoclonus, cervical dystonia, and akathisia. Immunotherapy was proven to be an effective treatment for the majority of instances.
      One potential problem in this study's approach is the small number of instances included in the analysis. With only 10 patients from 8 papers, the sample size is tiny, which may restrict the findings' generalizability. Furthermore, the use of case reports and case series for data gathering may create bias and variability in the reported results. Future research should aim for a bigger sample size and consider doing a more rigorous and systematic examination of the existing literature.
      Another potential flaw in the methodology is the absence of specific information supplied on the vaccines administered to patients. distinct vaccines may have distinct modes of action and potential side effects, influencing the development of movement disorders. Incorporating information about the individual vaccine administered to each patient would enable a more detailed investigation of the potential link between vaccination and movement disorders. Future research should seek to gather and analyze this extra information.
      In the future, researchers may consider undertaking a prospective cohort study to assess the occurrence of movement problems after immunization. This would enable a more thorough and controlled research into the potential link between immunization and movement disorders. Furthermore, introducing a control group of individuals who did not develop movement abnormalities following immunization could aid in the understanding of potential risk factors and mechanisms. Overall, future research in this field should aim to increase the quality and reliability of evidence on the link between immunization and movement disorders.

      March 21, 2024

      Add a comment
      Figure

      JMD : Journal of Movement Disorders Twitter