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Research paper
Functional neurological disorders in Parkinson disease
  1. Benjamin D Wissel1,
  2. Alok K Dwivedi2,
  3. Aristide Merola1,
  4. Danielle Chin1,
  5. Cara Jacob1,
  6. Andrew P Duker1,
  7. Jennifer E Vaughan1,
  8. Lilia Lovera1,
  9. Kathrin LaFaver3,
  10. Ariel Levy4,5,
  11. Anthony E Lang4,5,
  12. Francesca Morgante6,7,
  13. Melissa Jill Nirenberg8,
  14. Christopher Stephen9,
  15. Nutan Sharma9,
  16. Alberto Romagnolo10,
  17. Leonardo Lopiano10,
  18. Bettina Balint11,12,13,
  19. Xin X Yu14,
  20. Kailash P Bhatia11,
  21. Alberto J Espay1
  1. 1Department of Neurology, Gardner Family Center for Parkinson’s Disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA
  2. 2Division of Biostatistics and Epidemiology, Department of Biomedical Sciences, Texas Tech University Health Sciences Center, El Paso, Texas, USA
  3. 3Department of Neurology, University of Louisville, Louisville, Kentucky, USA
  4. 4Department of Neurology, Morton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson’s Disease, Toronto Western Hospital, Toronto, Canada
  5. 5The Department of Medicine, University of Toronto, Toronto, Canada
  6. 6Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Messina, Messina, Italy
  7. 7Institute of Molecular and Clinical Sciences, St George’s University of London, London, UK
  8. 8Department of Neurology, NYU School of Medicine, New York, USA
  9. 9Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, USA
  10. 10Department of Neuroscience “Rita Levi Montalcini”, University of Turin, Torino, Italy
  11. 11Sobell Department of Motor Neuroscience and Movement Disorders, University College London, London, UK
  12. 12Department of Neurology, University Hospital, Heidelberg, Germany
  13. 13Autoimmune Neurology Group, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  14. 14Cleveland Clinic Center for Neurological Restoration, Cleveland, USA
  1. Correspondence to Dr Alberto J Espay, Department of Neurology, Gardner Family Center for Parkinson’s Disease and Movement Disorders, University of Cincinnati, Cincinnati, OH 45267-0525, USA; alberto.espay{at}uc.edu

Abstract

Objective To ascertain demographic and clinical features of Parkinson disease (PD) associated with functional neurological features.

Methods A standardised form was used to extract data from electronic records of 53 PD patients with associated functional neurological disorders (PD-FND) across eight movement disorders centres in the USA, Canada and Europe. These subjects were matched for age, gender and disease duration to PD patients without functional features (PD-only). Logistic regression analysis was used to compare both groups after adjusting for clustering effect.

Results Functional symptoms preceded or co-occurred with PD onset in 34% of cases, nearly always in the most affected body side. Compared with PD-only subjects, PD-FND were predominantly female (68%), had longer delay to PD diagnosis, greater prevalence of dyskinesia (42% vs 18%; P=0.023), worse depression and anxiety (P=0.033 and 0.025, respectively), higher levodopa-equivalent daily dose (972±701 vs 741±559 mg; P=0.029) and lower motor severity (P=0.019). These patients also exhibited greater healthcare resource utilisation, higher use of [(123)I]FP-CIT SPECT and were more likely to have had a pre-existing psychiatric disorder (P=0.008) and family history of PD (P=0.036).

Conclusions A subtype of PD with functional neurological features is familial in one-fourth of cases and associated with more psychiatric than motor disability and greater use of diagnostic and healthcare resources than those without functional features. Functional manifestations may be prodromal to PD in one-third of patients.

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Footnotes

  • Contributors BDW contributed to organization and execution of the research project, review and critique of the statistical analysis, and drafting of the first draft. AKD contributed to the execution of the statistical analysis and review and critique of the manuscript. DC, CJ, AD, AM, JV, LL, KL, AL, AEL, FM, MJN, CS, NS, AR, LL, BB, XY, and KPB contributed to the execution of the research project and the review and critique of the manuscript. AJE contributed to the conception of the research project, organization and execution as well as review and critique of the statistical analysis and manuscript.

  • Funding The study was investigator initiated.

  • Competing interests BDW is supported by the NIH (T32GM063483-14). AKD is supported by the NIH (1R01HL125016-01) as a co-investigator and (R21 AI118228) as a collaborator. He has been also serving as a statistician in 4 CPRIT grants (PP110156, PP140211, PP150031 and PP130083), Coldwell (co-investigator), MSA Coalition (collaborator) and as a PI in TTUHSC ELP mini seed grant. AKD is a director of biostatistics & epidemiology consulting lab at the TTUHSC ELP. AM is supported by the NIH (KL2 TR001426). He has received speaker honoraria from CSL Behring, and Cynapsus Therapeutics. He has received grant support from Lundbeck. CJ has received honoraria from UCB. AJD has served as a consultant for Merz Pharmaceuticals, US World Meds and Auspex Pharmaceuticals and has received honoraria from UCB. LL has served as a consultant for Merz Pharmaceuticals. KLF has received research funding from the NIH, Vaccinex and honoraria from Pfizer and Teva. AL is funded by a Parkinson Canada Clinical Fellowship award and has received consulting honoraria from Transperfect Translations. AEL has served as an adviser for AbbVie, Allon Therapeutics, Avanir Pharmaceuticals, Biogen Idec, Boehringer Ingelheim, Bristol-Myers Squibb, Ceregene, Cipla, InteKrin, Lilly, Medtronic, Merck, Novartis, NeuroPhage Pharmaceuticals, Teva and UCB; received honoraria from Medtronic, Teva, UCB and AbbVie; received grants from Brain Canada, the Canadian Institutes of Health Research, the Edmond J. Safra Philanthropic Foundation, The Michael J. Fox Foundation, the Ontario Brain Institute, National Parkinson Foundation, Parkinson Society Canada, Physicians Services Incorporated (PSI), Tourette Syndrome Association, W. Garfield Weston Foundation; received publishing royalties from Saunders, Wiley-Blackwell, Johns Hopkins Press, and Cambridge University Press; and has served as an expert witness in cases related to the welding industry. FM has received honoraria as a Consultant & Advisory Boards from Medtronic, UCB and Chiesi. She has received honoraria for speaking from UCB Pharma, Medtronic, Zambon, Chiesi and Abbvie. She serves on the Editorial board of Movement Disorders Clinical Practice and Frontiers in Movement Disorders. She receives royalties from publication of Disorders of Movement (Springer, 2016). MJN has received research support from the New York Stem Cell Foundation, and honoraria from the American academy of neurology and the Parkinson’s disease foundation. CS has received grant support from the U Penn Orphan disease center million dollar bike ride/NTSAD. NS is supported by the NIH and has received personal compensation as a consultant for Allergan. AR has received grant support and speaker honoraria from AbbVie, speaker honoraria from Chiesi Farmaceutici and travel grants from Lusofarmaco and UCB Pharma. LL has received honoraria for lecturing and travel grants from Medtronic, UCB Pharma and AbbVie. BB is supported by the EAN research fellowship and the Robert Bosch Foundation. XXY reports no disclosures. KPB has received grant support from welcome/MRC, NIHR, Parkinson’s UK and EU horizon 2020. He has received royalties from publication of the Oxford Specialist Handbook Parkinson’s Disease and Other Movement Disorders (Oxford University Press, 2008, 2016) and of Marsden’s Book of Movement Disorders (Oxford University Press, 2013). He has received honoraria/personal compensation for participating as consultant/scientific board member from Ipsen, Allergan, Merz and honoraria for speaking at meetings and from Allergan, Ipsen, Merz, Sun Pharma, Teva, UCB Pharmaceuticals and from the American Academy of Neurology and movement disorders society. AJE is supported by the NIH and has received grant support from CleveMed/Great Lakes Neurotechnologies, Davis Phinney Foundation and the Michael J Fox Foundation; personal compensation as a consultant/scientific advisory board member for Solvay, Abbott, Chelsea Therapeutics, TEVA, Impax, Merz, Lundbeck and Eli Lilly; honoraria from TEVA, UCB, the American academy of Neurology and the movement disorders society; and publishing royalties from Lippincott Williams & Wilkins, Cambridge University Press and Springer.

  • Patient consent Detail has been removed from this case description/these case descriptions to ensure anonymity. The editors and reviewers have seen the detailed information available and are satisfied that the information backs up the case the authors are making.

  • Ethics approval The study was approved by all local ethics review boards. The Institutional Review Board of the University of Cincinnati actedas central for all sites (# 2016-1518).

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

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