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Comprehensive Study of Early Features in Spinocerebellar Ataxia 2: Delineating the Prodromal Stage of the Disease

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Abstract

The prodromal phase of spinocerebellar ataxias (SCAs) has not been systematically studied. Main findings come from a homogeneous SCA type 2 (SCA2) population living in Cuba. The aim of this study was to characterize extensively the prodromal phase of SCA2 by several approaches. Thirty-seven non-ataxic SCA2 mutation carriers and its age- and sex-matched controls underwent clinical assessments, including standardized neurological exam, structured interviews and clinical scales, and looking for somatic and autonomic features, as well as a neuropsychological battery, antisaccadic recordings, and MRI scans. Main clinical somatic features of non-ataxic mutation carriers were cramps, sensory symptoms, sleep disorders, and hyperreflexia, whereas predominating autonomic symptoms were pollakiuria/nocturia, constipation, and frequent throat clearing. Cognitive impairments included early deficits of executive functions and visual memory, suggesting the involvement of cerebro-cerebellar-cerebral loops and/or reduced cholinergic basal forebrain input to the cortex. Antisaccadic task revealed impaired oculomotor inhibitory control but preserved ability for error correction. Cognitive and antisaccadic deficits were higher as carriers were closer to the estimated onset of ataxia, whereas higher Scale for the Assessment and Rating of Ataxia (SARA) scores were associated most notably to vermis atrophy. The recognition of early features of SCA2 offers novel insights into the prodromal phase and physiopathological base of the disease, allowing the assessment of its progression and the efficacy of treatments, in particular at early phases when therapeutical options should be most effective.

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Acknowledgments

We are grateful to the non-ataxic SCA2 mutation carriers and the control individuals, as well as to the Cuban Ministry of Public Health, the National Council of Science and Technology of Mexico (CONACyT), and the Ibero-Latin American network for Movement disorders (RIBERMOV) for their cooperation.

Conflict of Interest

The authors declare that there are no conflicts of interest.

Funding Statement

This work was supported by the Cuban Ministry of Public Health and the CONACyT fellowship-203861 to L-VP.

Contributorship Statement

Luis Velázquez-Perez: Drafting the manuscript for content, study concept or design, acquisition of data, analysis or interpretation of data, study supervision or coordination, and final approval of the version to be published.

Roberto Rodríguez-Labrada: Study concept or design, drafting the manuscript for content, acquisition of data, analysis or interpretation of data, study supervision or coordination, and final approval of the version to be published.

Edilia M. Cruz Rivas: Acquisition of data, analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

Juan Fernandez-Ruiz: Acquisition of data, analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

Jandy Lilia-Campins: Acquisition of data, analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

Bulmaro Cisneros: Acquisition of data, analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

Israel Vaca-Palomares: Acquisition of data, analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

Arnoy Peña-Acosta: Acquisition of data and revising the manuscript for content.

Yaimeé Vazquez-Mojena: Acquisition of data, analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

Rosalinda Diaz: Acquisition of data, analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

Jonathan J Magaña-Aguirre: Acquisition of data, analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

Tania Cruz-Mariño: Acquisition of data, analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

Annelié Estupiñan-Rodríguez: Acquisition of data, analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

José M. Laffita-Mesa: Acquisition of data, analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

Rigoberto González-Piña: Acquisition of data, analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

Nalia Canales-Ochoa: Analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

Yanetza Gonzalez-Zaldivar: Acquisition of data, analysis or interpretation of data, revising the manuscript for content, and final approval of the version to be published.

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Authors and Affiliations

  1. Center for the Research and Rehabilitation of Hereditary Ataxias, Libertad Street 26, Holguín, 80100, Cuba

    Luis Velázquez-Pérez, Roberto Rodríguez-Labrada, Arnoy Peña-Acosta, Yaimeé Vázquez-Mojena, Tania Cruz-Mariño, Annelié Estupiñán-Rodríguez, José M. Laffita-Mesa, Nalia Canales-Ochoa & Yanetza González-Zaldivar

  2. Clinical-Surgical Hospital “Lucía Iñiguez”, Holguín, Cuba

    Edilia M. Cruz-Rivas & Jandy Lilia-Campins

  3. Neuropsychology Laboratory, Physiology Department, Medicine School, UNAM, Mexico City, Mexico

    Juan Fernández-Ruiz, Israel Vaca-Palomares & Rosalinda Diaz

  4. Department of Genetics and Molecular Biology, CINVESTAV-IPN, Mexico City, Mexico

    Bulmaro Cisneros

  5. Laboratory of Genomic Medicine, Department of Genetics, INR, Mexico City, Mexico

    Jonathan J. Magaña-Aguirre

  6. Department of Brain Plasticity, National Rehabilitation Institute (INR), Mexico City, Mexico

    Rigoberto González-Piña

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  1. Luis Velázquez-Pérez
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  2. Roberto Rodríguez-Labrada
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Correspondence to Luis Velázquez-Pérez.

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Velázquez-Pérez, L., Rodríguez-Labrada, R., Cruz-Rivas, E.M. et al. Comprehensive Study of Early Features in Spinocerebellar Ataxia 2: Delineating the Prodromal Stage of the Disease. Cerebellum 13, 568–579 (2014). https://doi.org/10.1007/s12311-014-0574-3

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