Minor Hallucinations Occur in Drug-Naive Parkinson’s Disease Patients, Even From the Premotor Phase Javier Pagonabarraga, MD, PhD, 1,2 Saul Martinez-Horta, BSc, 2,3,4 Ram on Fern andez de Bobadilla, BSc, 2,3,4 Jes us P erez, MD, 2,3 Roser Ribosa-Nogu e, MD, 2,3 Juan Mar  ın, MD, 2,3 Berta Pascual-Sedano, MD, PhD, 1,2,4 Carmen Garc  ıa, BSc, PhD, 1,2 Alexandre Gironell, MD, PhD, 1,2 and Jaime Kulisevsky, MD, PhD 1,2,3,4,5 * 1 Movement Disorders Unit, Neurology Department Sant Pau Hospital, Barcelona, Spain 2 Universitat Aut onoma de Barcelona, Spain 3 Biomedical Research Institute (IIB-Sant Pau), Barcelona, Spain 4 Universitat Oberta de Catalunya (UOC), Spain 5 Centro de Investigaci on en Red-Enfermedades Neurodegenerativas (CIBERNED), Spain ABSTRACT: Objectives: The description of minor hallucinatory phenomena (presence, passage hallucina- tions) has widened the spectrum of psychosis in Parkin- son’s disease (PD). Minor hallucinatory phenomena seem to antedate the development of more severe hallucinations. Early detection of minor hallucinations may be useful for screening patients with more severe endophenotypes. Motivated by the observation of “de novo,” drug-naive PD patients reporting minor hallucinations, we aimed to pro- spectively identify “de novo” untreated PD patients experi- encing hallucinatory phenomena, and to compare their clinico-demographic characteristics with those of untreated PD patients without hallucinations and healthy controls. Methods: Screening and description of psychosis was assessed by the Movement Disorders Society Unified Parkinson’s Disease Rating Scale—Part I and a structured interview covering all types of psychotic phe- nomena reported in PD. Clinical, neuropsychological, and demographic data of PD patients with and without psychotic phenomena were compared with those of age- and education-matched healthy controls. Results: Fifty drug-naive, “de novo” PD patients and 100 controls were prospectively included. Minor halluci- nations were experienced in 42% (21 of 50) PD patients and 5% controls (P < 0.0001). Coexistence of passage and presence hallucinations was the most common finding. Unexpectedly, 33.3% of patients with minor hal- lucinations manifested these as a pre-motor symptom, starting 7 months to 8 years before first parkinsonian motor symptoms. The presence of minor hallucinations was significantly associated with presence of rapid eye movement sleep behavior disorder. Conclusions: In this first study to prospectively ana- lyze the frequency of minor hallucinatory phenomena in incident, untreated PD patients, hallucinations appeared as a frequent early non-motor symptom that may even predate the onset of parkinsonism. V C 2015 International Parkinson and Movement Disorder Society Key Words: Parkinson’s disease; hallucinations; premotor; REM sleep behavior disorder; early untreated; drug-naive Hallucinations are significantly more common in Lewy body disorders than in other neurodegenerative diseases. 1-3 In parkinsonian disorders, visual hallucina- tions differentiate Parkinson’s disease (PD) from other non–Lewy-body causes of parkinsonism, predicting postmortem Lewy pathology with 93% accuracy. 4 Hallucinations in PD have been considered a mental complication that appears within the second half of the disease. 4 Nevertheless, minor hallucinatory phe- nomena, such as presence and passage hallucinations, have been described in up to 30% of patients in early stages of PD. 2,5,6 Minor hallucinatory phenomena include presence hallucinations (or feeling of pres- ence), passage hallucinations, and visual illusions. A presence hallucination is the vivid sensation that some- body (distinct from oneself) is present nearby, in the absence of sensory clues revealing a presence. Passage ------------------------------------------------------------ *Correspondence to: Dr. Jaime Kulisevsky, MD, PhD, Movement Disorders Unit, Neurology Department, Sant Pau Hospital, Mas Casanovas 90-08041, Barcelona, Spain, E-mail: jkulisevsky@santpau.cat Funding agencies: The present research was funded by CIBERNED (Fundaci  on CIEN, Instituto de Salud Carlos III, Spain). Relevant conflicts of interest/financial disclosures: Nothing to report. Author roles may be found in the online version of this article. Received: 9 July 2015; Revised: 22 August 2015; Accepted: 1 September 2015 Published online 00 Month 2015 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.26432 RESEARCH ARTICLE Movement Disorders, Vol. 00, No. 00, 2015 1