{"doi":"10.1002/mdc3.14175","title":"The Whistle‐Smile Reflex in Parkinson's Disease: A Cross‐Sectional Study","abstract":"Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor and nonmotor symptoms, including facial abnormalities such as hypomimia, which significantly impacts social interactions and life quality in patients.1 Hypomimia, also known as ‘facial bradykinesia',1 denotes a diminished facial expressiveness, encompassing reduced spontaneous blinking, decreased eyelid/eyebrow movements, and a reduction in facial movements involving the lower part, for example, grimacing and smiling.1, 2 In this context, the “whistle-smile” reflex (WSR), or Hanes sign, was first described in 1943 by Dr. Frederic Hanes, who observed that when healthy individuals are prompted to whistle during a medical examination, they typically comply and subsequently smile, reacting to the request's incongruity.3 However, when PD patients receive the same instruction, they execute the whistle but often fail to produce an immediate smile. Despite its potential diagnostic value, the WSR has seen limited clinical use, and only 2 reports, including Hanes's original work, explored this sign in PD.3, 4 In the present study, we examined the WSR in a broad sample of PD patients compared to age- and gender-matched healthy controls (HCs) to evaluate its sensitivity and specificity as a diagnostic marker. We enrolled 34 PD patients (assessed with their regular dopaminergic therapy) and 34 HCs (Table S1). The study was approved by local ethics committees, and informed consent was obtained from participants. Clinical evaluations included standardized scales. Video recordings followed standardized protocols (Supplementary Materials: Data S1). Briefly, participants' faces were recorded in a relaxed state for 30 seconds while looking at the camera (spontaneous facial expression videos). Participants were then asked to perform a whistle, and the recording continued for the next 15 s (WSR videos). Offline video editing was performed to ensure a blinded assessment (Supplementary Materials: Data S1). Videos were randomized and presented to 4 experienced movement disorders evaluators, unaware of the participants' diagnoses. Evaluators rated the severity of hypomimia per the Movement Disorders Society-sponsored version of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS), item 3.2, as well as the WSR, indicating whether they observed an immediate smile after whistling. Inter-rater agreement was computed using Fleiss’ K coefficient. Further data analyses are included in Supplementary Materials: Data S1. The overall agreement among raters in the assessment of the spontaneous facial expression videos was moderate (Fleiss’ K value: 0.45). We found a higher score in item 3.2 of the MDS-UPDRS scale Part III in PD patients compared to HCs (Supplementary Figure S1). The overall agreement among raters in the WSR video evaluation was substantial (Fleiss’ K value: 0.73). We found that 76.47% of PD patients did not exhibit a smile after whistling, compared to 35.29% of HCs (Video 1 and Supplementary Figure S2). The WSR showed a sensitivity of 76% and a specificity of 65% as a PD diagnostic marker. Logistic regression analysis revealed a correlation between the absence of WSR and the severity of hypomimia but not with cognitive or emotional impairment (Supplementary Materials: Data S1). The present study demonstrates the absence of the WSR in most of the PD patients tested employing a validated experimental approach and suggested it as a feature of an aberrant facial expressiveness automaticity. Taking into account some limitations inherent to our experimental approach (see Supplementary Materials: Data S1), the WSR could be an additional clinical sign to use in patient assessment, possibly in the early or prodromal disease phases.5 Further research is needed to validate the results of the present study. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical analysis: A. Design, B. Execution, C. Review and critique; (3) Manuscript: A. Writing o","journal":"Movement Disorders Clinical Practice","year":2024,"id":468745,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9693,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":373825,"name":"Luca Marsili","orcid":"0000-0002-6438-9911","position":1,"is_corresponding":false},{"id":658633,"name":"Kevin R. Duque","orcid":"0000-0002-5981-3140","position":2,"is_corresponding":false},{"id":1302235,"name":"Lucrezia Balestrucci","orcid":null,"position":3,"is_corresponding":false},{"id":1302236,"name":"Adriana Martini","orcid":null,"position":4,"is_corresponding":false},{"id":1301794,"name":"Antonio Cannavacciuolo","orcid":"0000-0002-1653-706X","position":5,"is_corresponding":false},{"id":1301795,"name":"Davide Costa","orcid":"0009-0008-6299-4449","position":6,"is_corresponding":false},{"id":1301796,"name":"Daniele Birreci","orcid":"0009-0004-8000-1886","position":7,"is_corresponding":false},{"id":1301797,"name":"Martina De Riggi","orcid":"0009-0002-2518-4259","position":8,"is_corresponding":false},{"id":1301798,"name":"Luca Angelini","orcid":"0000-0002-6601-7476","position":9,"is_corresponding":false},{"id":233015,"name":"Alberto J. Espay","orcid":"0000-0002-3389-136X","position":10,"is_corresponding":false},{"id":566229,"name":"Matteo Bologna","orcid":"0000-0003-0165-0833","position":11,"is_corresponding":false},{"id":1022254,"name":"Giulia Paparella","orcid":"0000-0002-7760-9442","position":0,"is_corresponding":true}],"reference_count":5,"raw_metadata":null,"created_at":"2026-07-19T02:05:23.500722Z","pmid":"39086089","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}