Skip to main content

Advertisement

SpringerLink
Log in

COVID-19 Impacts the Mental Health and Speech Function in Spinocerebellar Ataxia Type 2: Evidences from a Follow-Up Study

  • RESEARCH
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Limited evidence suggests that the SARS-CoV-2 infection can accelerate the progression of neurodegenerative diseases, but this has been not verified in the spinocerebellar ataxias (SCA). The objective of this study is to assess the impact of COVID-19 on the mental health and motor features of SCA2. A follow-up study was carried out in 170 Cuban SCA2 subjects and 87 community controls between 2020 and 2021. All subjects underwent a structured questionnaire to assess the risks of exposure to COVID-19, the confirmation of COVID-19 diagnosis, and the Hospital Anxiety and Depression Scale (HADS). Moreover, 36 subjects underwent the Scale for the Assessment and Rating of ataxia (SARA). The risk of exposure to SARS-CoV-2 and the frequency of COVID-19 were similar between the ataxia cohort and the community controls. Within the ataxia group, significantly increased HADS scores existed at the 2nd visit in both groups, but this increase was more evident for the infected group regarding the depression score. Moreover, a significant within-group increase of SARA score was observed in the infected group but not the non-infected group, which was mainly mediated by the significant increase of the speech item score in the infected group. Similar results were observed within the subgroup of preclinical carriers. Our study identified no selective vulnerability nor protection to COVID-19 in SCA2, but once infected, the patients experienced a deterioration of mental health and speech function, even at preclinical disease stage. These findings set rationales for tele-health approaches that minimize the detrimental effect of COVID-19 on SCA2 progression and identify SCA2 individuals as clinical model to elucidate the link between SARS-CoV-2 infection and neurodegeneration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data Availability

This dataset is not publicly available and can be asked from the Cuban authors directly upon reasonable request.

References

  1. Pollard CA, Morran MP, Nestor-Kalinoski AL. The COVID-19 pandemic: a global health crisis. Physiol Genomics. 2020;52:549–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bauer L, Laksono BM, de Vrij FMS, Kushner SA, Harschnitz O, van Riel D. The neuroinvasiveness, neurotropism, and neurovirulence of SARS-CoV-2. Trends Neurosci [Internet]. 2022;45:358–68. Available from: https://doi.org/10.1016/j.tins.2022.02.006.

  3. Misra S, Kolappa K, Prasad M, Radhakrishnan D, Thakur KT, Solomon T, et al. Frequency of neurologic manifestations in COVID-19. Neurology. 2021;97:E2269-81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Chou SHY, Beghi E, Helbok R, Moro E, Sampson J, Altamirano V, et al. Global incidence of neurological manifestations among patients hospitalized with COVID-19 - a report for the GCS-NeuroCOVID consortium and the ENERGY consortium. JAMA Netw Open. 2021;4:1–14.

    Article  Google Scholar 

  5. Monje M, Iwasaki A. The neurobiology of long COVID. Neuron [Internet]. 2022;110:3484–96. Available from: https://doi.org/10.1016/j.neuron.2022.10.006.

  6. Sakibuzzaman M, Hassan A, Hayee S, Haque FA, Bushra SS, Maliha M, et al. Exacerbation of pre-existing neurological symptoms with COVID-19 in patients with chronic neurological diseases: an updated systematic review. Cureus. 2022;14(9):e29297.

  7. Rutkai I, Mayer MG, Hellmers LM, Ning B, Huang Z, Monjure CJ, et al. Neuropathology and virus in brain of SARS-CoV-2 infected non-human primates. Nat Commun [Internet]. 2022;13:1745. Available from: https://www.nature.com/articles/s41467-022-29440-z. Accessed 21 Mar 2023

  8. Shaikh AG, Manto M, Mitoma H. 2 years into the pandemic: what did we learn about the COVID-19 and cerebellum? Cerebellum [Internet]. 2022;21:19–22. Available from: https://doi.org/10.1007/s12311-021-01351-7.

  9. González-Garcés Y, Domínguez-Barrios Y, Zayas-Hernández A, Sigler-Villanueva AA, Canales-Ochoa N, Hernández Oliver MO, et al. Impacts of the COVID-19 pandemic on the mental health and motor deficits in Cuban patients with cerebellar ataxias. The Cerebellum [Internet]. 2021;20:896–903. Available from: https://link.springer.com/10.1007/s12311-021-01260-9.

  10. Gong Y, Chen Z, Liu M, Wan L, Wang C, Peng H, et al. Anxiety and depression in spinocerebellar ataxia patients during the COVID-19 pandemic in China: a cross-sectional study. J Clin Neurosci [Internet]. 2021;88:39–46. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0967586821001144. Accessed 21 Dec 2021

  11. Singh I, Swarup V, Shakya S, Kumar V, Gupta D, Rajan R, et al. Impact of SARS-CoV-2 infection in spinocerebellar ataxia 12 patients. Mov Disord. 2021;36:2459–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Schirinzi T, Sancesario A, Castelli E, Bertini E, Vasco G. Friedreich ataxia in COVID-19 time: current impact and future possibilities. Cerebellum & Ataxias [Internet]. 2021;8:4. Available from: https://cerebellumandataxias.biomedcentral.com/articles/10.1186/s40673-020-00127-9. Accessed 12 Jan 2021

  13. Shen MM, Rodden LN, McIntyre K, Arias A, Profeta V, Schadt K, et al. SARS-CoV-2 in patients with Friedreich ataxia. J Neurol [Internet]. 2023;270:610–3. Available from: https://doi.org/10.1007/s00415-022-11419-x.

  14. Faltin K, Lewandowska Z, Małeckia P, Czyż K, Szafran E, Kowalska-Tupko A, et al. SARS-CoV-2 attacks the weakest point - COVID-19 course in a pediatric patient with Friedreich’s ataxia. Int J Infect Dis. 2022;117:284–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Velázquez-Pérez L, Medrano-Montero J, Rodríguez-Labrada R, Canales-Ochoa N, CampinsAlí J, Carrillo Rodes FJ, et al. Hereditary ataxias in Cuba: a nationwide epidemiological and clinical study in 1001 patients. Cerebellum. 2020;19:252–64.

    Article  PubMed  Google Scholar 

  16. Almaguer-Mederos LE, Falcón NS, Almira YR, Zaldivar YG, Almarales D, Gongora EH, Herrera MP, Armiñan RR, Manresa MV, Cruz GS, Laffita-Mesa J, Cruz TM, Chang V, Auburger G, Gispert SPL. Estimation of the age at onset in spinocerebellar ataxia type 2 Cuban patients by survival analysis. Clin Genet. 2010;78:169–74.

    Article  CAS  PubMed  Google Scholar 

  17. Snaith RP. The hospital anxiety and depression scale. Health Qual Life Outcomes. 2003;10:1–11.

    Google Scholar 

  18. Schmitz-Hubsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, et al. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology [Internet]. 2006;66:1717–20. Available from: https://www.neurology.org/lookup/doi/10.1212/01.wnl.0000219042.60538.92.

  19. Bonenfant G, Williams N, Netzband R, Schwarz MC, Evans MJ, Pager CT. Zika virus subverts stress granules to promote and restrict viral gene expression. J Virol. 2019;93(12):e00520-19

  20. Jagdeo JM, Dufour A, Klein T, Solis N, Kleifeld O, Kizhakkedathu J, et al. N-Terminomics TAILS identifies host cell substrates of poliovirus and coxsackievirus B3 3C proteinases that modulate virus infection. Pfeiffer JK, editor. J Virol [Internet]. 2018;92. Available from: https://journals.asm.org/doi/10.1128/JVI.02211-17. Accessed 9 Sept 2020

  21. Elden AC, Kim H-J, Hart MP, Chen-Plotkin AS, Johnson BS, Fang X, et al. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. Nature [Internet]. 2010;466:1069–75. Available from: https://www.nature.com/articles/nature09320.

  22. Rubino E, Mancini C, Boschi S, Ferrero P, Ferrone M, Bianca S, et al. ATXN2 intermediate repeat expansions influence the clinical phenotype in frontotemporal dementia. Neurobiol Aging [Internet]. 2019;73:231.e7-231.e9. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0197458018303324.

  23. Reynaldo Armiñan RD, Reynaldo Hernández R, Paneque Herrera M, Prieto Ávila L, Pérez Ruiz E. Trastornos mentales en pacientes con ataxia espinocerebelosa tipo 2 cubana. Rev Neurol [Internet]. 2002;35:818. Available from: https://www.neurologia.com/articulo/2002300.

  24. Zhu C, Zhang T, Li Q, Chen X, Wang K. Depression and anxiety during the COVID-19 pandemic: epidemiology, mechanism, and treatment. Neurosci Bull [Internet]. 2022;39:675–84. Available from: https://doi.org/10.1007/s12264-022-00970-2.

  25. Miconi D, Li ZY, Frounfelker RL, Santavicca T, Cénat JM, Venkatesh V. Ethno-cultural disparities in mental health during the COVID-19 pandemic : a cross-sectional study on the impact of exposure to the virus and COVID-19-related discrimination and stigma on mental health across ethno-cultural groups in Quebec (Canada). BJPsych Open. 2021;7(1): e14. Available from: https://doi.org/10.1192/bjo.2020.146.

  26. Tancredi S, Ulytė A, Wagner C, Keidel D, Witzig M, Imboden M, et al. Changes in socioeconomic resources and mental health after the second COVID - 19 wave (2020–2021): a longitudinal study in Switzerland. Int J Equity Health. 2023;22(1):51. https://doi.org/10.1186/s12939-023-01853-2.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Willey B, Mimmack K, Gagliardi G, Dossett ML, Wang S, Udeogu OJ. Racial and socioeconomic status differences in stress , posttraumatic growth , and mental health in an older adult cohort during the COVID-19 pandemic. eClinicalMedicine [Internet]. 2022;45:101343. Available from: https://doi.org/10.1016/j.eclinm.2022.101343.

  28. Di Pietro DA, Olivares A, Comini L, Vezzadini G, Luisa A, Petrolati A, et al. Voice alterations, dysarthria, and respiratory derangements in patients with Parkinson’s disease. J Speech, Lang Hear Res [Internet]. 2022;65:3749–57. Available from: http://pubs.asha.org/doi/10.1044/2022_JSLHR-21-00539. Accessed 29 Sept 2023

  29. Sarmet M, Santos DB, Mangilli LD, Million JL, Maldaner V, Zeredo JL. Chronic respiratory failure negatively affects speech function in patients with bulbar and spinal onset amyotrophic lateral sclerosis: retrospective data from a tertiary referral center. Logop Phoniatr Vocology [Internet]. 2022;1–10. Available from: https://www.tandfonline.com/doi/full/10.1080/14015439.2022.2092209. Accessed 28 Sept 2023

  30. Vázquez‐Mojena Y, Rodríguez‐Córdova Y, Dominguez‐Barrios Y, León‐Arcia K, Miranda‐Becerra D, Gonzalez‐Zaldivar Y, et al. Peripheral inflammation links with the severity of clinical phenotype in spinocerebellar ataxia 2. Mov Disord [Internet]. 2023;38:880–5. Available from: https://movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29359.

  31. Vogel AP, Magee M, Torres-Vega R, Medrano-Montero J, Cyngler MP, Kruse M, et al. Features of speech and swallowing dysfunction in pre-ataxic spinocerebellar ataxia type 2. Neurology [Internet]. 2020;95:e194–205. Available from: https://www.neurology.org/lookup/doi/10.1212/WNL.0000000000009776.

  32. Fodoulian L, Tuberosa J, Rossier D, Boillat M, Kan C, Pauli V, et al. SARS-CoV-2 Receptors and Entry genes are expressed in the human olfactory neuroepithelium and brain. iScience [Internet]. 2020;23:101839. Available from: https://linkinghub.elsevier.com/retrieve/pii/S2589004220310361. Accessed 23 Mar 2022

  33. Matschke J, Lütgehetmann M, Hagel C, Sperhake JP, Schröder AS, Edler C, et al. Neuropathology of patients with COVID-19 in Germany: a post-mortem case series. Lancet Neurol. 2020;19:919–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Fabbri VP, Foschini MP, Lazzarotto T, Gabrielli L, Cenacchi G, Gallo C, et al. Brain ischemic injury in COVID‐19‐infected patients: a series of 10 post‐mortem cases. Brain Pathol [Internet]. 2021;31:205–10. Available from: https://onlinelibrary.wiley.com/doi/10.1111/bpa.12901. Accessed 1 Apr 2022

  35. Chan JL, Murphy KA, Sarna JR. Myoclonus and cerebellar ataxia associated with COVID-19: a case report and systematic review. J Neurol [Internet]. 2021;268:3517–48. Available from: https://doi.org/10.1007/s00415-021-10458-0

  36. Marcelo A, Afonso IT, Afonso-Reis R, Brito DVC, Costa RG, Rosa A, et al. Autophagy in Spinocerebellar ataxia type 2, a dysregulated pathway, and a target for therapy. Cell Death Dis [Internet]. 2020;12:1117. Available from: https://www.nature.com/articles/s41419-021-04404-1.

  37. Wardman JH, Henriksen EE, Marthaler AG, Nielsen JE, Nielsen TT. Enhancement of autophagy and solubilization of ataxin-2 alleviate apoptosis in spinocerebellar ataxia type 2 patient cells. The Cerebellum [Internet]. 2020;19:165–81. Available from: http://link.springer.com/10.1007/s12311-019-01092-8.

  38. Arsović A, Halbach MV, Canet-Pons J, Esen-Sehir D, Döring C, Freudenberg F, Czechowska N, Seidel K, Baader SL, Gispert S, Sen N-E, Auburger G. Mouse ataxin-2 expansion downregulates camkii and other calcium mouse ataxin-2 expansion downregulates camkii and other calcium signaling factors, impairing granule — Purkinje neuron synaptic strength. Int J Mol Sci. 2020;21:6673.

  39. Almaguer-Gotay D, Almaguer-Mederos LE, Aguilera-Rodríguez R, Estupiñán-Rodríguez A, González-Zaldivar Y, Cuello-Almarales D, et al. Role of glutathione S-transferases in the spinocerebellar ataxia type 2 clinical phenotype. J Neurol Sci. 2014;341:41–5.

    Article  CAS  PubMed  Google Scholar 

  40. Meierhofer D, Halbach M, Şen NE, Gispert S, Auburger G. Ataxin-2 (Atxn2)-knock-out mice show branched chain amino acids and fatty acids pathway alterations. Mol Cell Proteomics. 2016;15:1728–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Almutairi MM, Sivandzade F, Albekairi TH, Alqahtani F, Cucullo L. Neuroinflammation and Its impact on the pathogenesis of COVID-19. Front Med [Internet]. 2021;8:1–14. Available from: https://www.frontiersin.org/articles/10.3389/fmed.2021.745789/full. Accessed 23 Jun 2023

  42. Nonhoff U, Ralser M, Welzel F, Piccini I, Balzereit D, Yaspo M, et al. Ataxin-2 Interacts with the DEAD/H-box RNA helicase DDX6 and interferes with P-bodies and stress granules. Weissman J, editor. Mol Biol Cell [Internet]. 2007;18:1385–96. Available from: https://www.molbiolcell.org/doi/10.1091/mbc.e06-12-1120.

  43. Wolozin B, Ivanov P. Stress granules and neurodegeneration. Nat Rev Neurosci [Internet]. 2019;20:649–66. Available from: https://doi.org/10.1038/s41583-019-0222-5

  44. Koppenol R, Conceição A, Afonso IT, Afonso-Reis R, Costa RG, Tomé S, et al. The stress granule protein G3BP1 alleviates spinocerebellar ataxia-associated deficits. Brain [Internet]. 2023;146:2346–63. Available from: https://academic.oup.com/brain/article/146/6/2346/6895270. Accessed 30 Jul 2023.

  45. Zheng ZQ, Wang SY, Xu ZS, Fu YZ, Wang YY. SARS-CoV-2 nucleocapsid protein impairs stress granule formation to promote viral replication. Cell Discov [Internet]. 2021;7. Available from: https://doi.org/10.1038/s41421-021-00275-0

  46. Schatton C, Synofzik M, Fleszar Z, Giese MA, Schöls L, Ilg W. Individualized exergame training improves postural control in advanced degenerative spinocerebellar ataxia: a rater-blinded, intra-individually controlled trial. Parkinsonism Relat Disord [Internet]. 2017;39:80–4. Available from: https://linkinghub.elsevier.com/retrieve/pii/S1353802017301116. Accessed 12 Jun  2023

  47. Grobe-Einsler M, Taheri Amin A, Faber J, Schaprian T, Jacobi H, Schmitz-Hübsch T, et al. Development of SARAhome, a new video-based tool for the assessment of ataxia at home. Mov Disord. 2021;36:1242–6.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank all SCA2 patients, preclinical carriers, and community controls for their willingness to participate in the study. We also thank the Cuban Network of Hereditary Ataxias for its contribution to the study. In addition, we acknowledge the Cuban Ministry of Science, Technology and Environment, the Ministry of Public Health of Cuba, and the Alexander von Humboldt Foundation for providing the funds for this study.

Funding

All Cuban authors received funding from the Cuban Ministry of Science and Technology (National Program of Neuroscience of Neurotechnology, project grant: PN305LH013-034) and the Cuban Ministry of Public Health. LVP, GA, and UZ received funding from the Alexander von Humboldt Foundation (Digital Cooperation Fellowship). None of the authors has received any other funding in the last 12 months relevant to this study.

Author information

Authors and Affiliations

  1. Centre for the Research and Rehabilitation of Hereditary Ataxias, Libertad 26, Holguín, Cuba

    Luis Velázquez-Pérez, Yasmany Gonzalez-Garcés, Nalia Canales-Ochoa, Jacqueline Medrano-Montero & Frank J. Carrillo-Rodes

  2. Cuban Academy of Sciences, Cuba St. 460, between Teniente Rey St., and Compostela St., Habana Vieja, 19100, Havana, Cuba

    Luis Velázquez-Pérez

  3. Cuban Centre for Neuroscience, Playa. 198 St, between 27 and 25th Ave., 16 Cubanacan 19818, Playa, 11300, Havana, Cuba

    Roberto Rodríguez-Labrada & Yaimeé Vázquez-Mojena

  4. Clinical & Surgical Hospital “Calixto Garcia”, Universidad avenue & J st, Vedado, 14 Plaza de la Revolución, 10400, Havana, Cuba

    Yennis Domínguez-Barrios

  5. University Hospital “Lucía Iñíguez”, “Celia Sánchez” Avenue 1, Holguín, Cuba

    María B. Ramírez-Bautista

  6. Clinical & Surgical Hospital “Guillermo Domínguez” Puerto Padre, Las Tunas, Cuba

    Alberto Caballero-Laguna

  7. University Hospital “Juan Bruno Zayas”, Carretera del Caney Street. Pastorita, Santiago de Cuba, Cuba

    Osiel Gámez-Rodríguez

  8. Pediatric Hospital “José Luis Miranda”, “26 de Julio” Avenida Escambray, Santa Clara, Cuba

    María O. Hernández-Oliver

  9. Polyclinic “Joel Benitez Borges”, Cauto Cristo, Granma, Cuba

    Yamilca Sosa-Cruz

  10. Polyclinic “Manuel Fajardo Rivero”, Urbano Noris, Holguín, Cuba

    Arianna Zayas-Hernández

  11. Department of Neurology and Stroke, Eberhard-Karls University of Tübingen, Hoppe-Seyler Str.3, 72076, Tübingen, Germany

    Ulf Ziemann

  12. Hertie-Institute for Clinical Brain Research, Eberhard-Karls University of Tübingen, 22 Hoppe-Seyler Str.3, 72076, Tübingen, Germany

    Ulf Ziemann

  13. Experimental Neurology, Faculty of Medicine, Goethe University, 24, 60590, Frankfurt, Germany

    Georg Auburger

Authors
  1. Luis Velázquez-Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roberto Rodríguez-Labrada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yasmany Gonzalez-Garcés
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nalia Canales-Ochoa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jacqueline Medrano-Montero
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yennis Domínguez-Barrios
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Frank J. Carrillo-Rodes
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. María B. Ramírez-Bautista
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Alberto Caballero-Laguna
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Osiel Gámez-Rodríguez
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. María O. Hernández-Oliver
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Yamilca Sosa-Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Arianna Zayas-Hernández
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Yaimeé Vázquez-Mojena
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Ulf Ziemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Georg Auburger
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization and study design: LVP and RRL

Literature search: LVP, RRL, and GA

Data collection: YGG, NCO, JMM, YDB, FJCR, MBRB, ACL, OGR, MOHO, YSC, AZH, and YVM

Data analysis: LVP and RRL

Data interpretation: LVP, RRL, UZ, and GA

Writing—original draft: RRL

Writing—review and editing: LVP, UZ, and GA

Corresponding authors

Correspondence to Luis Velázquez-Pérez or Roberto Rodríguez-Labrada.

Ethics declarations

Ethical Approval and Consent to Participate

The study protocol was approved by the ethics committee of the Centre for the Research and Rehabilitation of Hereditary Ataxias and was in accordance with the declaration of Helsinki. All participants gave their written informed consent prior to the assessments.

Competing Interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Luis Velázquez-Pérez is the senior author.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Velázquez-Pérez, L., Rodríguez-Labrada, R., Gonzalez-Garcés, Y. et al. COVID-19 Impacts the Mental Health and Speech Function in Spinocerebellar Ataxia Type 2: Evidences from a Follow-Up Study. Cerebellum (2023). https://doi.org/10.1007/s12311-023-01612-7

Download citation

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12311-023-01612-7

Keywords

Search

Navigation