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Pontocerebellar atrophy is the hallmark neuroradiological finding in late-onset Tay-Sachs disease

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Abstract

Purpose

Late-onset Tay-Sachs disease (LOTS) is a form of GM2 gangliosidosis, an autosomal recessive neurodegenerative disorder characterized by slowly progressive cerebellar ataxia, lower motor neuron disease, and psychiatric impairment due to mutations in the HEXA gene. The aim of our work was to identify the characteristic brain MRI findings in this presumably underdiagnosed disease.

Methods

Clinical data and MRI findings from 16 patients (10F/6 M) with LOTS from two centers were independently assessed by two readers and compared to 16 age- and sex-related controls.

Results

Lower motor neuron disease (94%), psychiatric symptoms—psychosis (31%), cognitive impairment (38%) and depression (25%)—and symptoms of cerebellar impairment including dysarthria (94%), ataxia (81%) and tremor (69%), were the most common clinical features. On MRI, pontocerebellar atrophy was a constant finding. Compared to controls, LOTS patients had smaller mean middle cerebellar peduncle diameter (p < 0.0001), mean superior cerebellar peduncle diameter (p = 0.0002), mesencephalon sagittal area (p = 0.0002), pons sagittal area (p < 0.0001), and larger 4th ventricle transversal diameter (p < 0.0001). Mild corpus callosum thinning (37.5%), mild cortical atrophy (18.8%), and white matter T2 hyperintensities (12.5%) were also present.

Conclusion

Given the characteristic clinical course and MRI findings of the pontocerebellar atrophy, late-onset Tay-Sachs disease should be considered in the differential diagnosis of adult-onset cerebellar ataxias.

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Data availability

De-identified individual participant data that underlie the results reported in this article will be shared upon reasonable request to the corresponding authors coming from researchers who provide a methodologically sound proposal.

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Funding

This study was supported by Czech Ministry of Health, grant Nr. RVO 64165. SAS was supported by the Stiftung Verum, the Ara Parseghian Medical Research Fund and the intramural Munich Clinician Scientist Programme. PD was funded by Czech Ministry of Health, grant No. NU21-04–00535, General University Hospital in Prague, grant No. 20-L-13, and European Union’s Horizon 2020 research and innovation programme, grant No. 633190.

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Authors and Affiliations

  1. Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic

    Jitka Májovská, Helena Jahnová & Martin Magner

  2. Department of Neurology, Ludwig-Maximilians University, Munich, Germany

    Anita Hennig & Susanne A. Schneider

  3. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    Igor Nestrasil

  4. Department of Radiology, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic

    Manuela Vaněčková & Petr Dušek

  5. Department of Pediatrics, University Thomayer Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic

    Martin Magner

  6. Department of Neurology and Center of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic

    Petr Dušek

Authors
  1. Jitka Májovská
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  2. Anita Hennig
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  3. Igor Nestrasil
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  4. Susanne A. Schneider
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  5. Helena Jahnová
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  6. Manuela Vaněčková
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  7. Martin Magner
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  8. Petr Dušek
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Correspondence to Petr Dušek.

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The study was approved by the Institutional Review Board of the General University Hospital in Prague (Ethic Committee Approval Number 1471/19).

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Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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Májovská, J., Hennig, A., Nestrasil, I. et al. Pontocerebellar atrophy is the hallmark neuroradiological finding in late-onset Tay-Sachs disease. Neurol Sci 43, 3273–3281 (2022). https://doi.org/10.1007/s10072-021-05757-3

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  • DOI: https://doi.org/10.1007/s10072-021-05757-3

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