Skip to main content

Advertisement

SpringerLink
Log in

Progression of Functional Gait in Hereditary Spastic Paraplegias

  • Original Article
  • Published:
The Cerebellum Aims and scope Submit manuscript

Abstract

Hereditary spastic paraplegias (HSP) are characterized by progressive deterioration of axonal projections of upper motor neurons leading to abnormal locomotion. The clinical course of HSP as well as the definition of the best instruments to assess its progression is largely unknown. The aim of this study was to investigate the progression of functional gait in individuals with HSP and to define sensitivity to change, minimal clinically important difference (MCID), and validity of timed functional tests of gait (TFT). The study was constituted of two phases: a cross-sectional study and a prospective cohort of 18 months. Twenty-five patients (17 being SPG4), and twenty-five age- and sex-matched control individuals performed TFT. Spastic paraplegia rating scale (SPRS), ten-meter walking test (10MWT), timed up and go test (TUG), both at self-selected and maximal walking speeds, and six-minute walking test (6MWT) were performed on baseline in both groups and after 18 months of follow-up only in the HSP cohort. In the cross-sectional analysis, all TFTs performances were greatly impaired in HSP patients compared to controls. After 18 months of follow-up, TFTs did not differ significantly from baseline in the statistical analysis, with some tests showing more frequent improvement than worsening. We have provided effect size measures and MCID for the evaluated instruments. HSPs clearly compromised TFTs performances, which were valid instruments for assessing disease severity. However, TFTs and SPRS did not capture the very slow motor evolution of HSPs, reinforcing the necessity of additional biomarkers of disease progression.

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

Similar content being viewed by others

References

  1. Shribman S, Reid E, Crosby AH, Houlden H, Warner TT. Hereditary spastic paraplegia: from diagnosis to emerging therapeutic approaches. Lancet Neurol. 2019;18(12):1136–46. https://doi.org/10.1016/S1474-4422(19)30235-2.

    Article  CAS  PubMed  Google Scholar 

  2. DeLuca GC, Ebers GC, Esiri MM. The extent of axonal loss in the long tracts in hereditary spastic paraplegia. Neuropathol Appl Neurobiol. 2004;30:576–84. https://doi.org/10.1111/j.1365-2990.2004.00587.

    Article  CAS  PubMed  Google Scholar 

  3. Burguez D, Polese-Bonattoc M, Scudeiro L, et al. Clinical and molecular characterization of hereditary spastic paraplegias: a next-generation sequencing panel approach. J Neurol Sci. 2017;383:18–25. https://doi.org/10.1016/j.jns.2017.10.010.

    Article  CAS  PubMed  Google Scholar 

  4. Klimpe S, Schüle R, Kassubek J, Otto S, Kohl Z, Klebe S, et al. Disease severity affects quality of life of hereditary spastic paraplegia patients. Eur J Neurol. 2012;19(1):168–71. https://doi.org/10.1111/j.1468-1331.2011.03443.x.

    Article  CAS  PubMed  Google Scholar 

  5. Schüle R, Wiethoff S, Martus P, Karle KN, Otto S, Klebe S, et al. Hereditary spastic paraplegia: clinicogenetic lessons from 608 patients. Ann Neurol. 2016;79(4):646–58. https://doi.org/10.1002/ana.24611.

    Article  PubMed  Google Scholar 

  6. Schule R, Holland-Letz T, Klimpe S, Kassubek J, Klopstock T, Mall V, et al. The Spastic Paraplegia Rating Scale (SPRS): a reliable and valid. Neurology. 2006;67(3):430–4. https://doi.org/10.1212/01.wnl.0000228242.53336.90.

    Article  CAS  PubMed  Google Scholar 

  7. Servelhere KR, Faber I, Coan AC, França M Jr. Translation and validation into Brazilian Portuguese of the Spastic Paraplegia Rating Scale (SPRS). Arq Neuropsiquiatr. 2016;74:6–494. https://doi.org/10.1590/0004-282X20160047.

    Article  Google Scholar 

  8. Busner J, Targum SD. The clinical global impressions scale: appling a research tool in clinical practice. Psychiatry (Edgmont). 2007;4(7):28–37.

    Google Scholar 

  9. Adell E, Wehmhörner S, Rydwik E. The test-retest reliability of 10 meters maximal walking speed in older people living in a residential care unit. J Geriatr Phys Ther. 2012;36(2):74–7. https://doi.org/10.1519/JPT.0b013e318264b8ed.

    Article  Google Scholar 

  10. Watson MJ. Refining the ten-metre walking test for use with neurologically impaired people. Physiotherapy. 2002;88(7):386–97. https://doi.org/10.1016/s0031-9406(05)61264.

    Article  Google Scholar 

  11. Podsiadlo D, Richardson S. The timed “Up & Go”: a test of basic functional mobility for frail elderly persons. J Am Geriatr Soc. 1991;39(2):142–8. https://doi.org/10.1111/j.1532-5415.1991.tb01616.x.

    Article  CAS  PubMed  Google Scholar 

  12. The American Thoracic Society. ATS statement: guidelines for the six-minute walk. Am J Respir Crit Care Med. 2002;166:111–7. https://doi.org/10.1164/rccm.166/1/111.

    Article  Google Scholar 

  13. Peyré-Tartaruga LA, Monteiro EP. A new integrative approach to evaluate pathological gait: locomotor rehabilitation index. Clin Transl Degener Dis. 2016;1(2):86–90. https://doi.org/10.4103/2468-5658.184750.

    Article  Google Scholar 

  14. Klebe S, Stolze H, Kopper F, Lorenz D, Wenzelburger R, Deuschl G, et al. Objective assessment of gait after intrathecal baclofen in hereditary spastic paraplegia. J Neurol. 2005;252:991–3. https://doi.org/10.1007/s00415-005-0792-1.

    Article  CAS  PubMed  Google Scholar 

  15. Zhang Y, Richard Roxburgh R, Huang L, et al. The effect of hydrotherapy treatment on gait characteristics of hereditary spastic paraparesis patients. Gait Posture. 2014;39(4):1074–9. https://doi.org/10.1016/j.gaitpost.2014.01.010.

    Article  PubMed  Google Scholar 

  16. Van Lith BJH, Den Boer J, Van de Warrenburg BPC, Weerdesteyn V, Geurts AC. Functional effects of botulinum toxin type A in the hip adductors and subsequent stretching in patients with hereditary spastic paraplegia. J Rehabil Med. 2019;51(6):434–41. https://doi.org/10.2340/16501977-2556.

    Article  PubMed  Google Scholar 

  17. Paparella G, Vavla M, Bernardi L, Girardi G, Stefan C, Martinuzzi A. Efficacy of a combined treatment of botulinum toxin and intensive physiotherapy in hereditary spastic paraplegia. Front Neurosci. 2020;14:111. https://doi.org/10.3389/fnins.2020.00111.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Harding AE. Classification of the hereditary ataxias and paraplegias. Lancet. 1983;1:8334–1155. https://doi.org/10.1016/S0140-6736(83)92879-9.

    Article  Google Scholar 

Download references

Acknowledgements

This study was funded by FIPE-HCPA (GPPG-HCPA 2017-0341). Arcila DMC is supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES). The authors thank Medical Genetics Division of Hospital de Clínicas de Porto Alegre for help recruiting patients; to the LAPEX for technical support of laboratories; to the NeMug and Locomotion research groups of the Universidade Federal do Rio Grande do Sul for discussions and comments on this project.

Funding

This study was funded by FIPE-HCPA (GPPG-HCPA 2017-0341). Cubillos-Arcila DM is supported by Coordination of Superior Level Staff Improvement - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

Author information

Author notes

  1. Diana Maria Cubillos Arcila and Gustavo Dariva Machado contributed equally to this work.

Authors and Affiliations

  1. Graduate Program in Medicine, Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Diana Maria Cubillos-Arcila & Jonas Alex Morales Saute

  2. Exercise Research Laboratory, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Diana Maria Cubillos-Arcila & Leonardo Alexandre Peyré-Tartaruga

  3. Medical Genetics division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Gustavo Dariva Machado, Lauren Sehnem, Daniela Burguêz & Jonas Alex Morales Saute

  4. Graduate Program in Human Movement Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Ana Paula Janner Zanardi, Valéria Feijó Martins & Leonardo Alexandre Peyré-Tartaruga

  5. Neurogenetics, Clinical Research Center, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Jonas Alex Morales Saute

  6. Neurology division, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil

    Jonas Alex Morales Saute

  7. Internal Medicine Department, Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil

    Jonas Alex Morales Saute

Authors
  1. Diana Maria Cubillos-Arcila
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gustavo Dariva Machado
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lauren Sehnem
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daniela Burguêz
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ana Paula Janner Zanardi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Valéria Feijó Martins
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Leonardo Alexandre Peyré-Tartaruga
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jonas Alex Morales Saute
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Diana Maria Cubillos Arcila: acquisition of data, analysis and interpretation of data, drafting the article and final approval of the version to be submitted.

Gustavo Dariva Machado: acquisition of data, analysis and interpretation of data, drafting the article and final approval of the version to be submitted.

Lauren Sehnem: acquisition of data and final approval of the version to be submitted.

Daniela Burguêz: acquisition of data and final approval of the version to be submitted.

Ana Paula Janner Zanardi: acquisition of data, revising the article critically for important intellectual content and final approval of the version to be submitted.

Valéria Feijó Martins: acquisition of data, revising the article critically for important intellectual content and final approval of the version to be submitted.

Leonardo Alexandre Peyré-Tartaruga: conception and design of the study, interpretation of data, revising the article critically for important intellectual content and final approval of the version to be submitted.

Jonas Alex Morales Saute: conception and design of the study, analysis and interpretation of data, drafting the article and final approval of the version to be submitted.

We state that the manuscript has been read and approved by all the authors that the requirements for authorship as stated in the journal’s instruction to the authors.

Corresponding author

Correspondence to Jonas Alex Morales Saute.

Ethics declarations

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

Additional information

Publisher’s Note

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

Supplementary Information

ESM 1

(DOCX 19 kb)

ESM 2

(DOCX 18 kb)

ESM 3

(DOCX 16 kb)

ESM 4

(DOCX 18 kb)

ESM 5

(DOCX 19 kb)

ESM 6

(DOCX 16 kb)

ESM 7

(DOCX 16 kb)

ESM 8

(DOCX 16 kb)

ESM 9

(DOCX 17 kb)

ESM 10

(DOCX 15 kb)

ESM 11

(TIF 3961 kb)

High resolution image (PNG 60 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cubillos-Arcila, D.M., Machado, G.D., Sehnem, L. et al. Progression of Functional Gait in Hereditary Spastic Paraplegias. Cerebellum 21, 350–357 (2022). https://doi.org/10.1007/s12311-021-01302-2

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12311-021-01302-2

Keywords

Search

Navigation