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Visual hallucinations and illusions in Parkinson’s disease: the role of ocular pathology

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Abstract

Introduction

Whether different mechanisms, particularly ocular pathology, could lead to the emergence of visual hallucinations (VH) (defined as false perceptions with no external stimulus) versus visual illusions (VI) (defined as a misperception of a real stimulus) in Parkinson’s disease (PD) remains debated. We assessed retinal, clinical and structural brain characteristics depending on the presence of VH or VI in PD.

Methods

In this case–control study, we compared retinal thickness using optical coherence tomography (OCT), between PD patients with: VI (PD-I; n = 26), VH (PD-H; n = 28), and without VI or VH (PD-C; n = 28), and assessed demographic data, disease severity, treatment, anatomical and functional visual complaints, cognitive and visuo-perceptive functions and MRI brain volumetry for each group of PD patients.

Results

Parafoveal retina was thinner in PD-H compared to PD-C (p = 0.005) and PD-I (p = 0.009) but did not differ between PD-I and PD-C (p = 0.85). Multivariate analysis showed that 1/retinal parafoveal thinning and total brain gray matter atrophy were independently associated with the presence of VH compared to PD-I; 2/retinal parafoveal thickness, PD duration, sleep quality impairment and total brain gray matter volume were independent factors associated with the presence of VH compared to PD-C; 3/anterior ocular abnormalities were the only factor independently associated with the presence of illusions compared to PD-C.

Conclusion

These findings reinforce the hypothesis that there may be different mechanisms contributing to VH and VI in PD, suggesting that these two entities may also have a different prognosis rather than simply lying along a continuous spectrum.

Registration number

Clinicaltrials.gov number NCT01114321.

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References

  1. Lenka A, Pagonabarraga J, Pal PK, Bejr-Kasem H, Kulisvesky J (2019) Minor hallucinations in Parkinson disease: a subtle symptom with major clinical implications. Neurology 93:259–266. https://doi.org/10.1212/WNL.0000000000007913

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fénelon G, Mahieux F, Huon R, Ziégler M (2000) Hallucinations in Parkinson’s disease: prevalence, phenomenology and risk factors. Brain 123(Pt 4):733–745

    Article  PubMed  Google Scholar 

  3. Biousse V, Skibell BC, Watts RL, Loupe DN, Drews-Botsch C, Newman NJ (2004) Ophthalmologic features of Parkinson’s disease. Neurology 62:177–180. https://doi.org/10.1212/01.wnl.0000103444.45882.d8

    Article  CAS  PubMed  Google Scholar 

  4. Pagonabarraga J, Martinez-Horta S, Fernández de Bobadilla R, Pérez J, Ribosa-Nogué R, Marín J, Pascual-Sedano B, García C, Gironell A, Kulisevsky J (2016) Minor hallucinations occur in drug-naive Parkinson’s disease patients, even from the premotor phase. Mov Disord 31:45–52. https://doi.org/10.1002/mds.26432

    Article  PubMed  Google Scholar 

  5. Goodwin FK (1971) Psychiatric side effects of levodopa in man. JAMA J Am Med Assoc 218:1915–1920. https://doi.org/10.1001/jama.218.13.1915

    Article  CAS  Google Scholar 

  6. Goetz CG, Vogel C, Tanner CM, Stebbins GT (1998) Early dopaminergic drug-induced hallucinations in parkinsonian patients. Neurology 51:811–814. https://doi.org/10.1212/wnl.51.3.811

    Article  CAS  PubMed  Google Scholar 

  7. Goetz CG, Ouyang B, Negron A, Stebbins GT (2010) Hallucinations and sleep disorders in PD: 10-year prospective longitudinal study. Neurology 75:1773–1779. https://doi.org/10.1212/WNL.0b013e3181fd6158

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ramírez-Ruiz B, Junqué C, Martí M-J, Valldeoriola F, Tolosa E (2006) Neuropsychological deficits in Parkinson’s disease patients with visual hallucinations. Mov Disord 21:1483–1487. https://doi.org/10.1002/mds.20965

    Article  PubMed  Google Scholar 

  9. Barnes J, Boubert L (2008) Executive functions are impaired in patients with Parkinson’s disease with visual hallucinations. J Neurol Neurosurg Psychiatry 79:190–192. https://doi.org/10.1136/jnnp.2007.116202

    Article  CAS  PubMed  Google Scholar 

  10. Lee J-Y, Kim JM, Ahn J, Kim H-J, Jeon BS, Kim TW (2014) Retinal nerve fiber layer thickness and visual hallucinations in Parkinson’s disease. Mov Disord 29:61–67. https://doi.org/10.1002/mds.25543

    Article  PubMed  Google Scholar 

  11. Štenc Bradvica I, Bradvica M, Matić S, Reisz-Majić P (2015) Visual dysfunction in patients with Parkinson’s disease and essential tremor. Neurol Sci 36:257–262. https://doi.org/10.1007/s10072-014-1930-2

    Article  PubMed  Google Scholar 

  12. Archibald NK, Clarke MP, Mosimann UP, Burn DJ (2011) Visual symptoms in Parkinson’s disease and Parkinson’s disease dementia. Mov Disord 26:2387–2395. https://doi.org/10.1002/mds.23891

    Article  PubMed  Google Scholar 

  13. Guo L, Normando EM, Shah PA, De Groef L, Cordeiro MF (2018) Oculo-visual abnormalities in Parkinson’s disease: possible value as biomarkers. Mov Disord 33:1390–1406. https://doi.org/10.1002/mds.27454

    Article  PubMed  Google Scholar 

  14. Urwyler P, Nef T, Killen A, Collerton D, Thomas A, Burn D, McKeith I, Mosimann UP (2014) Visual complaints and visual hallucinations in Parkinson’s disease. Parkinsonism Relat Disord 20:318–322. https://doi.org/10.1016/j.parkreldis.2013.12.009

    Article  PubMed  Google Scholar 

  15. Archibald NK, Clarke MP, Mosimann UP, Burn DJ (2009) The retina in Parkinson’s disease. Brain 132:1128–1145. https://doi.org/10.1093/brain/awp068

    Article  PubMed  Google Scholar 

  16. O’Brien J, Taylor JP, Ballard C, Barker RA, Bradley C, Burns A, Collerton D, Dave S, Dudley R, Francis P, Gibbons A, Harris K, Lawrence V, Leroi I, McKeith I, Michaelides M, Naik C, O’Callaghan C, Olsen K, Onofrj M, Pinto R, Russell G, Swann P, Thomas A, Urwyler P, Weil RS, Ffytche D (2020) Visual hallucinations in neurological and ophthalmological disease: pathophysiology and management. J Neurol Neurosurg Psychiatry 91:512–519. https://doi.org/10.1136/jnnp-2019-322702

    Article  PubMed  Google Scholar 

  17. Borm CDJM, Visser F, Werkmann M, de Graaf D, Putz D, Seppi K, Poewe W, Vlaar AMM, Hoyng C, Bloem BR, Theelen T, de Vries NM (2020) Seeing ophthalmologic problems in Parkinson disease: results of a visual impairment questionnaire. Neurology 94:e1539–e1547. https://doi.org/10.1212/WNL.0000000000009214

    Article  PubMed  PubMed Central  Google Scholar 

  18. Visser M, Verbaan D, van Rooden SM, Stiggelbout AM, Marinus J, van Hilten JJ (2007) Assessment of psychiatric complications in Parkinson’s disease: the SCOPA-PC. Mov Disord 22:2221–2228. https://doi.org/10.1002/mds.21696

    Article  PubMed  Google Scholar 

  19. Wong BM, Cheng RW, Mandelcorn ED, Margolin E, El-Defrawy S, Yan P, Santiago AT, Leontieva E, Lou W, ONDRI Investigators, Hatch W, Hudson C (2019) Validation of optical coherence tomography retinal segmentation in neurodegenerative disease. Transl Vis Sci Technol. https://doi.org/10.1167/tvst.8.5.6

    Article  PubMed  PubMed Central  Google Scholar 

  20. Ellis AW, Brysbaert M (2010) Split fovea theory and the role of the two cerebral hemispheres in reading: a review of the evidence. Neuropsychologia 48:353–365. https://doi.org/10.1016/j.neuropsychologia.2009.08.021

    Article  PubMed  Google Scholar 

  21. Yarmohammadi A, Zangwill LM, Diniz-Filho A, Saunders LJ, Suh MH, Wu Z, Manalastas PIC, Akagi T, Medeiros FA, Weinreb RN (2017) Peripapillary and macular vessel density in patients with glaucoma and single-hemifield visual field defect. Ophthalmology 124:709–719. https://doi.org/10.1016/j.ophtha.2017.01.004

    Article  PubMed  Google Scholar 

  22. de Chazeron I, Pereira B, Chereau-Boudet I, Brousse G, Misdrahi D, Fénelon G, Tronche A-M, Schwan R, Lançon C, Marques A, Debilly B, Durif F, Llorca PM (2015) Validation of a Psycho-Sensory hAllucinations Scale (PSAS) in schizophrenia and Parkinson’s disease. Schizophr Res 161:269–276. https://doi.org/10.1016/j.schres.2014.11.010

    Article  PubMed  Google Scholar 

  23. Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE (2010) Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord 25:2649–2653. https://doi.org/10.1002/mds.23429

    Article  PubMed  Google Scholar 

  24. Rapport LJ, Millis SR, Bonello PJ (1998) Validation of the Warrington theory of visual processing and the visual object and space perception battery. J Clin Exp Neuropsychol 20:211–220. https://doi.org/10.1076/jcen.20.2.211.1169

    Article  CAS  PubMed  Google Scholar 

  25. Agniel A, Joanette Y, Doyon B, Duchein C (1992) Protocole Montréal Toulouse d’Evaluation des Gnosies Visuelles PEGV. Ortho-Edition, Isberg

    Google Scholar 

  26. Chaudhuri KR, Pal S, DiMarco A, Whately-Smith C, Bridgman K, Mathew R, Pezzela FR, Forbes A, Högl B, Trenkwalder C (2002) The Parkinson’s disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinson’s disease. J Neurol Neurosurg Psychiatr 73:629–635

    Article  CAS  Google Scholar 

  27. Postuma RB, Arnulf I, Hogl B, Iranzo A, Miyamoto T, Dauvilliers Y, Oertel W, Ju Y-E, Puligheddu M, Jennum P, Pelletier A, Wolfson C, Leu-Semenescu S, Frauscher B, Miyamoto M, Cochen De Cock V, Unger MM, Stiasny-Kolster K, Fantini ML, Montplaisir JY (2012) A single-question screen for rapid eye movement sleep behavior disorder: a multicenter validation study. Mov Disord 27:913–916. https://doi.org/10.1002/mds.25037

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kopal A, Mejzlíková E, Preiningerová JL, Brebera D, Ulmanová O, Ehler E, Roth J (2015) Changes of retina are not involved in the genesis of visual hallucinations in Parkinson’s disease. Parkinsons Dis 2015:709191. https://doi.org/10.1155/2015/709191

    Article  PubMed  PubMed Central  Google Scholar 

  29. Meppelink AM, de Jong BM, Renken R, Leenders KL, Cornelissen FW, van Laar T (2009) Impaired visual processing preceding image recognition in Parkinson’s disease patients with visual hallucinations. Brain 132:2980–2993. https://doi.org/10.1093/brain/awp223

    Article  PubMed  Google Scholar 

  30. Ramírez-Ruiz B, Martí M-J, Tolosa E, Giménez M, Bargalló N, Valldeoriola F, Junqué C (2007) Cerebral atrophy in Parkinson’s disease patients with visual hallucinations. Eur J Neurol 14:750–756. https://doi.org/10.1111/j.1468-1331.2007.01768.x

    Article  PubMed  Google Scholar 

  31. Ibarretxe-Bilbao N, Ramirez-Ruiz B, Junque C, Marti MJ, Valldeoriola F, Bargallo N, Juanes S, Tolosa E (2010) Differential progression of brain atrophy in Parkinson’s disease with and without visual hallucinations. J Neurol Neurosurg Psychiatry 81:650–657. https://doi.org/10.1136/jnnp.2009.179655

    Article  PubMed  Google Scholar 

  32. Harding AJ, Stimson E, Henderson JM, Halliday GM (2002) Clinical correlates of selective pathology in the amygdala of patients with Parkinson’s disease. Brain 125:2431–2445. https://doi.org/10.1093/brain/awf251

    Article  PubMed  Google Scholar 

  33. Diederich NJ, Goetz CG, Raman R, Pappert EJ, Leurgans S, Piery V (1998) Poor visual discrimination and visual hallucinations in Parkinson’s disease. Clin Neuropharmacol 21:289–295

    CAS  PubMed  Google Scholar 

  34. Matsui H, Udaka F, Tamura A, Oda M, Kubori T, Nishinaka K, Kameyama M (2006) Impaired visual acuity as a risk factor for visual hallucinations in Parkinson’s disease. J Geriatr Psychiatry Neurol 19:36–40. https://doi.org/10.1177/0891988705284739

    Article  PubMed  Google Scholar 

  35. Barnes J, Boubert L, Harris J, Lee A, David AS (2003) Reality monitoring and visual hallucinations in Parkinson’s disease. Neuropsychologia 41:565–574

    Article  CAS  PubMed  Google Scholar 

  36. Diederich NJ, Goetz CG, Stebbins GT (2005) Repeated visual hallucinations in Parkinson’s disease as disturbed external/internal perceptions: focused review and a new integrative model. Mov Disord 20:130–140. https://doi.org/10.1002/mds.20308

    Article  PubMed  Google Scholar 

  37. Muller AJ, Shine JM, Halliday GM, Lewis SJG (2014) Visual hallucinations in Parkinson’s disease: theoretical models. Mov Disord 29:1591–1598. https://doi.org/10.1002/mds.26004

    Article  PubMed  Google Scholar 

  38. Collerton D, Perry E, McKeith I (2005) Why people see things that are not there: a novel Perception and Attention Deficit model for recurrent complex visual hallucinations. Behav Brain Sci 28:737–757. https://doi.org/10.1017/S0140525X05000130

    Article  PubMed  Google Scholar 

  39. Shine JM, Halliday GM, Naismith SL, Lewis SJG (2011) Visual misperceptions and hallucinations in Parkinson’s disease: dysfunction of attentional control networks? Mov Disord 26:2154–2159. https://doi.org/10.1002/mds.23896

    Article  PubMed  Google Scholar 

  40. Lefebvre S, Baille G, Jardri R, Plomhause L, Szaffarczyk S, Defebvre L, Thomas P, Delmaire C, Pins D, Dujardin K (2016) Hallucinations and conscious access to visual inputs in Parkinson’s disease. Sci Rep 6:36284. https://doi.org/10.1038/srep36284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. O’Callaghan C, Hall JM, Tomassini A, Muller AJ, Walpola IC, Moustafa AA, Shine JM, Lewis SJG (2017) Visual hallucinations are characterized by impaired sensory evidence accumulation: insights from hierarchical drift diffusion modeling in Parkinson’s disease. Biol Psychiatry Cogn Neurosci Neuroimaging 2:680–688. https://doi.org/10.1016/j.bpsc.2017.04.007

    Article  PubMed  Google Scholar 

  42. Pagonabarraga J, Soriano-Mas C, Llebaria G, López-Solà M, Pujol J, Kulisevsky J (2014) Neural correlates of minor hallucinations in non-demented patients with Parkinson’s disease. Parkinsonism Relat Disord 20:290–296. https://doi.org/10.1016/j.parkreldis.2013.11.017

    Article  PubMed  Google Scholar 

  43. Lee W-W, Yoon EJ, Lee J-Y, Park S-W, Kim YK (2017) Visual hallucination and pattern of brain degeneration in Parkinson’s disease. Neurodegener Dis 17:63–72. https://doi.org/10.1159/000448517

    Article  PubMed  Google Scholar 

  44. Nishio Y, Yokoi K, Hirayama K, Ishioka T, Hosokai Y, Gang M, Uchiyama M, Baba T, Suzuki K, Takeda A, Mori E (2018) Defining visual illusions in Parkinson’s disease: Kinetopsia and object misidentification illusions. Parkinsonism Relat Disord 55:111–116. https://doi.org/10.1016/j.parkreldis.2018.05.023

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors gratefully acknowledge Anna Sontheimer for her advices in MRI morphometric statistical analysis, Stacey West for English language editing, and participants and caregivers who contributed to this study for their commitment. The authors also acknowledge Fondation de France who supported this work (Grant no. 76354).

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Authors and Affiliations

  1. Neurology Department, Université Clermont-Auvergne, EA7280, Clermont-Ferrand University Hospital, Clermont-Ferrand, France

    Ana Marques, Marie Fontaine, Philippe Derost, Bérengère Debilly, Isabelle Rieu & Franck Durif

  2. Ophtalmology Department, Université Clermont-Auvergne, EA7280, Clermont-Ferrand University Hospital, Clermont-Ferrand, France

    Steven Beze, Nathalie Monneyron, Celine Lambert & Frédéric Chiambaretta

  3. Biostatistics Department, Clermont-Ferrand University Hospital, Clermont-Ferrand, France

    Bruno Pereira

  4. Imaging Department, Université Clermont-Auvergne, EA7280, Clermont-Ferrand University Hospital, Clermont-Ferrand, France

    Carine Chassain

  5. CMRR, Clermont-Ferrand University Hospital, Clermont-Ferrand, France

    Laure Delaby

  6. Brain and Mind Center, Parkinson’s Disease Research Clinic, University of Sydney, Sydney, Australia

    Simon J. G. Lewis

Authors
  1. Ana Marques
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  2. Steven Beze
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  3. Bruno Pereira
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  8. Marie Fontaine
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Contributions

Statistical analysis conducted by: BP and CL; Clermont-Ferrand University Hospital, Biostatistics Department, Clermont-Ferrand, France.

Corresponding author

Correspondence to Ana Marques.

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Conflicts of interest

Ana Marques, Steven Beze, Bruno Pereira, Carine Chassain, Nathalie Monneyron, Laure Delaby, Celine Lambert, Marie Fontaine, Philippe Derost, Bérengère Debilly, Isabelle Rieu, Simon Lewis, Frédéric Chiambaretta, Franck Durif—report no disclosures.

Ethical statement

The protocol was approved by the South-West and Overseas II ethical committee, France (clinicaltrials.gov number NTC03454269).

Informed consent

All patients gave their written informed consent as per the Declaration of Helsinki.

Electronic supplementary material

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Supplementary file4 (PDF 137 kb)

415_2020_9925_MOESM5_ESM.tiff

Supplementary file5 Sample segmented image from a PD-C subject. Sagittal, coronal and axial images show typical automated subcortical segmentation results from Freesurfer. Different brain regions are indicated by different colors, for example hippocampus appears in gold, putamen in pink, and caudate and pallidum in two different shades of light blue. Total volumes are automatically extracted for each label, with separate values for left and right hemisphere in most structures. (TIFF 246 kb)

415_2020_9925_MOESM6_ESM.tiff

Supplementary file6 Heatmap representation of correlation coefficients between brain volumes, retinal thickness and clinical data. Correlation coefficients (Spearman r) are color-coded as shown on the Horizontal bar on top of the figure. UPDRS: Unified Parkinson Disease Rating Scale; LED: levodopa equivalent dose; DA: dopamine agonists; PDSS: Parkinson disease scale; SCOPA-PC: Scales for outcomes in Parkinson’s disease - Psychiatric complications; PSAS: psychiatric symptom assessment scale; UM-PDHQ: university of Miami Parkinson’s disease hallucinations questionnaire. (TIFF 2703 kb)

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Marques, A., Beze, S., Pereira, B. et al. Visual hallucinations and illusions in Parkinson’s disease: the role of ocular pathology. J Neurol 267, 2829–2841 (2020). https://doi.org/10.1007/s00415-020-09925-x

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  • DOI: https://doi.org/10.1007/s00415-020-09925-x

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