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Comorbid alpha synucleinopathies in idiopathic normal pressure hydrocephalus

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Abstract

Objective

This study aimed to determine the prevalence and clinical features of Parkinson’s disease (PD)/PD dementia (PD/PDD) or dementia with Lewy bodies (DLB) in idiopathic normal pressure hydrocephalus (iNPH).

Methods

Patients with iNPH who were admitted to the Department of Neurology, Juntendo University School of Medicine over the past 10 years have been retrospectively analyzed. The diagnosis of iNPH and concomitant PD/PDD or DLB was established using diagnostic criteria. Motor symptoms were assessed by the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) III. 123I-ioflupane single-photon emission computed tomography (DaT-SPECT) and cerebrospinal fluid (CSF) real-time quaking-induced conversion (RT-QuIC)-based assay were performed for alpha synuclein aggregation.

Results

Overall, 79 patients met the criteria for iNPH, of which 34 developed iNPH without accompanying disorders (iNPHa; 43%), 23 developed iNPH with comorbid PD/PDD (iNPHc + PD/PDD; 29.1%), and 8 developed iNPH with comorbid DLB (iNPHc + DLB; 10.1%). Significant differences in facial expansion and upper-limb parkinsonism were observed with a comorbidity of either PD/PDD or DLB. The specific binding ratio (SBR) of DaTscan was reduced in iNPHa (p = 0.02), but it reduced further with comorbid PD/PDD (p < 0.01) or DLB (p < 0.01). RT-QuIC was positive for all 13 comorbid PD/PDD and negative for all 19 iNPHa.

Conclusion

These results highlight that synucleinopathies coexist with iNPH. These can be differentiated by performing DaTscan and RT-QuIC, which can affect its clinical features.

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Summary data will be shared by qualified researchers.

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Funding

The authors have no relevant financial or non-financial interests to disclose.

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Authors and Affiliations

  1. Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo Bynkyo-ku, Tokyo, 113-8421, Japan

    Anri Sakurai, Taiji Tsunemi, Yuta Ishiguro, Ayami Okuzumi, Taku Hatano & Nobutaka Hattori

Authors
  1. Anri Sakurai
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  2. Taiji Tsunemi
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  3. Yuta Ishiguro
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  4. Ayami Okuzumi
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  5. Taku Hatano
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  6. Nobutaka Hattori
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Contributions

AS: collected data, conducted statistical analysis, and wrote the draft. YI: collected samples. Ayami Okuzumi conducted RT-QuIC. TH: edited the draft. TT: Initiated and organized the project and finalized the manuscript. NH: organized the project.

Corresponding author

Correspondence to Taiji Tsunemi.

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Conflicts of interest

Anri Sakurai, Taiji Tsunemi, Yuta Ishiguro, Ayami Okuzumi, Taku Hatano and Nobutaka Hattori have no conflict of interest to declare.

Ethics approval

This study protocol complied with the Declaration of Helsinki and was approved by the ethics committee of Juntendo University.

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Informed consent was obtained from all individual participants.

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The participants have consented to the submission of this manuscript to the journal.

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Sakurai, A., Tsunemi, T., Ishiguro, Y. et al. Comorbid alpha synucleinopathies in idiopathic normal pressure hydrocephalus. J Neurol 269, 2022–2029 (2022). https://doi.org/10.1007/s00415-021-10778-1

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  • DOI: https://doi.org/10.1007/s00415-021-10778-1

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