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Neurodegeneration
Original research
Distinct dopaminergic abnormalities in traumatic brain injury and Parkinson’s disease
  1. Peter Owen Jenkins1,
  2. Andreas-Antonios Roussakis2,
  3. Sara De Simoni1,
  4. Niall Bourke1,
  5. Jessica Fleminger1,
  6. James Cole1,
  7. Paola Piccini2,
  8. David Sharp1,3
  1. 1 Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences, Imperial College, London, United Kingdom
  2. 2 Centre for Neuroinflammation and Neurodegeneration, Division of Brain Sciences, Imperial College London, London, UK
  3. 3 UK Dementia Research Institute, Care Research & Technology Centre, Imperial College, London, United Kingdom
  1. Correspondence to Dr David Sharp, Imperial College, London SW7 2AZ, UK; david.sharp{at}imperial.ac.uk

Abstract

Objective Traumatic brain injury (TBI) and rapid eye movement sleep behavioural disorder (RBD) are risk factors for Parkinson’s disease (PD). Dopaminergic abnormalities are often seen after TBI, but patients usually lack parkinsonian features. We test whether TBI, PD and RBD have distinct striatal dopamine abnormalities using dopamine transporter (DaT) imaging.

Methods 123I-ioflupane single-photon emission CT scans were used in a cross-sectional study to measure DaT levels in moderate/severe TBI, healthy controls, patients with early PD and RBD. Caudate and putamen DaT, putamen to caudate ratios and left-right symmetry of DaT were compared.

Results 108 participants (43 TBI, 26 PD, 8 RBD, 31 controls) were assessed. Patients with early PD scored significantly higher on the Unified Parkinson’s Disease Rating Scale motor subscale than other groups. Patients with TBI and PD had reduced DaT levels in the caudate (12.2% and 18.7%, respectively) and putamen (9.0% and 42.6%, respectively) compared with controls. Patients with RBD had reduced DaT levels in the putamen (12.8%) but not in the caudate compared with controls. Patients with PD and TBI showed distinct patterns of DaT reduction, with patients with PD showing a lower putamen to caudate ratio. DaT asymmetry was greater in the PD group than other groups.

Conclusions The results show that patients with early PD and TBI have distinct patterns of striatal dopamine abnormalities. Patients with early PD and moderate/severe TBI showed similar reductions in caudate DaT binding, but patients with PD showed a greater reduction in putamen DaT and a lower putamen to caudate ratio. The results suggest that parkinsonian motor signs are absent in these patients with TBI because of relatively intact putaminal dopamine levels.

https://doi.org/10.1136/jnnp-2019-321759

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    Footnotes

    • Twitter @nialljbourke, @neurosharp

    • Contributors POJ, A-AR, SDS, PP and DS contributed to the conception and design of the study. POJ, A-AR, SDS, NB, JF, JC, PP and DS all contributed to the acquisition and analysis of the data. POJ, A-AR, PP and DS were responsible for the bulk of drafting the manuscript.

    • Funding This paper presents independent research funded by a National Institute of Health Research Professorship (NIHR-RP-011-048) awarded to DS and supported by the NIHR CRF and Biomedical Research Centre at Imperial College Healthcare NHS Trust. DS was funded by a National Institute of Health Research Professorship (NIHR-RP-011-048). POJ is funded by Guarantors of Brain Clinical Fellowship. PP received funding from the Michael J Fox Foundation for Parkinson’s Research.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Ethics approval This study was reviewed and approved by the West London and GTAC Research Ethics Committee, UK and the Administration of Radioactive Substances Advisory Committee, UK.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available on reasonable request. Anonymised data will be shared on request through personal correspondence.