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Prediagnostic motor and non-motor symptoms in progressive supranuclear palsy: The step-back PSP study

  • Cèlia Painous
    Affiliations
    Parkinson's Disease & Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Parkinson's Disease and Other Degenerative Movement Disorders Team, European Reference Network for Rare Neurological Diseases (ERN-RND), IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII), Institut Clínic de Neurociències (Maria de Maeztu Center), Universitat de Barcelona, Barcelona, Catalonia, Spain
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  • Maria J Martí
    Affiliations
    Parkinson's Disease & Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Parkinson's Disease and Other Degenerative Movement Disorders Team, European Reference Network for Rare Neurological Diseases (ERN-RND), IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII), Institut Clínic de Neurociències (Maria de Maeztu Center), Universitat de Barcelona, Barcelona, Catalonia, Spain
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  • Cristina Simonet
    Affiliations
    Parkinson's Disease & Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Parkinson's Disease and Other Degenerative Movement Disorders Team, European Reference Network for Rare Neurological Diseases (ERN-RND), IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII), Institut Clínic de Neurociències (Maria de Maeztu Center), Universitat de Barcelona, Barcelona, Catalonia, Spain

    Preventive Neurology Unit, Wolfson Institute of Preventive Medicine, London, UK
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  • Alícia Garrido
    Affiliations
    Parkinson's Disease & Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Parkinson's Disease and Other Degenerative Movement Disorders Team, European Reference Network for Rare Neurological Diseases (ERN-RND), IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII), Institut Clínic de Neurociències (Maria de Maeztu Center), Universitat de Barcelona, Barcelona, Catalonia, Spain
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  • Francesc Valldeoriola
    Affiliations
    Parkinson's Disease & Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Parkinson's Disease and Other Degenerative Movement Disorders Team, European Reference Network for Rare Neurological Diseases (ERN-RND), IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII), Institut Clínic de Neurociències (Maria de Maeztu Center), Universitat de Barcelona, Barcelona, Catalonia, Spain
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  • Esteban Muñoz
    Affiliations
    Parkinson's Disease & Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Parkinson's Disease and Other Degenerative Movement Disorders Team, European Reference Network for Rare Neurological Diseases (ERN-RND), IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII), Institut Clínic de Neurociències (Maria de Maeztu Center), Universitat de Barcelona, Barcelona, Catalonia, Spain
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  • Ana Cámara
    Affiliations
    Parkinson's Disease & Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Parkinson's Disease and Other Degenerative Movement Disorders Team, European Reference Network for Rare Neurological Diseases (ERN-RND), IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII), Institut Clínic de Neurociències (Maria de Maeztu Center), Universitat de Barcelona, Barcelona, Catalonia, Spain
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  • Yaroslau Compta
    Correspondence
    Corresponding author. Neurology Service, Hospital Clínic de Barcelona, 170 Villarroel street, 08036, Barcelona, Spain.
    Affiliations
    Parkinson's Disease & Movement Disorders Unit, Neurology Service, Hospital Clínic de Barcelona, Parkinson's Disease and Other Degenerative Movement Disorders Team, European Reference Network for Rare Neurological Diseases (ERN-RND), IDIBAPS, Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED:CB06/05/0018-ISCIII), Institut Clínic de Neurociències (Maria de Maeztu Center), Universitat de Barcelona, Barcelona, Catalonia, Spain
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      Highlights

      • Motor and non-motor prediagnostic PSP symptoms have not been studied in depth.
      • We retrospectively assessed prediagnostic symptoms in PSP vs. PD and controls.
      • Prediagnostic falls but also gait, cognitive and mood disturbances were more frequent in PSP.
      • These symptoms might help define prediagnostic PSP.
      • These might assist selection of enriched populations in future PSP research.

      Abstract

      Background

      Improved knowledge of the prediagnostic phase of progressive supranuclear palsy (PSP) might provide information on when and how the disease starts, along with the opportunity to test therapies in disease stages with lesser neurodegeneration.

      Objective

      To explore the symptoms in years preceding the PSP diagnosis.

      Methods

      This is a single-center retrospective case-control study based on clinical charts review and a structured interview to PSP patients and their caregivers. Prediagnostic symptoms were defined as those present more than one year before the diagnosis. We explored 35 symptoms in the following domains: visual, dizziness, motor, mood/apathy, cognitive, behavioral, sleep, gastrointestinal/urinary and miscellaneous. Non-parametric statistics were applied, with significance set at <0.05 (FDR-corrected).

      Results

      We included 150 subjects: 50 PSP patients (38% females, age 75.8) and an age- and sex-matched control group of 50 Parkinson's disease (PD) and 50 subjects (CS) without neurodegenerative disease. The frequencies of visual, motor, cognitive, behaviour and dizziness domains were significantly higher in PSP vs. PD, and so were the motor, mood/apathy, cognitive, behaviour and dizziness ones in PSP vs. CS. Over 50% of prediagnostic falls, apathy and anxiety, depression and memory-attention-executive symptoms, and over 30% of gait disturbances started more than three and up to ten years before the diagnosis. PSP patients had more consultations to ENT and ophthalmologists than PD patients.

      Conclusion

      PSP patients present a broad variety of motor and non-motor symptoms several years before the diagnosis. The definition of a prediagnostic PSP phase might be helpful to identify patients in early disease stages.

      Keywords

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