Groaning in Progressive Supranuclear Palsy: Insights From a Large Asian Cohort

BACKGROUND: Although regularly encountered, the groaning phenomenon in progressive supranuclear palsy (PSP) currently lacks systematic investigation. OBJECTIVES: We investigated the frequency and clinical phenomenology of groaning in PSP. METHODS: We assessed 180 patients with PSP, identifying groaning through examination and history. A specially designed questionnaire captured groaning characteristics (intensity, frequency, and triggers). Scores for the PSP Clinical Deficits Scale (PSP-CDS), Barthel Index (BI), Short Cognitive and Neuropsychiatric Assessment (ShoCo) Scale, and modified Zarit Burden Interview (ZBI), and whole exome sequencing (WES) data, were extracted from our research database. RESULTS: Thirty-six (20.0%) patients exhibited groaning, most of whom (77.8%) had Richardson's syndrome (PSP-RS), which predicted groaning with an odds ratio (OR) of 4.1 (95% CI = 1.7-10.3, P = 0.002). Worse disease severity (PSP-CDS) was also a predictive factor (OR = 1.2, 95% CI = 1.1-1.3, P = 0.002). Additionally, patients with groaning demonstrated worse longitudinal disease trajectory, alongside significantly greater functional disability (BI), cognitive-behavioral impairment (ShoCo), and caregiver burden (ZBI). Groaning was typically moderate in intensity or loud, considered troublesome by caregivers and/or patients, and triggers or reasons were commonly identified (in 76.0%). WES showed several patients carrying pathogenic/likely pathogenic variants in genes potentially relevant to PSP (MAPT, GBA1, and SMPD1), but none carried the rare NEFH variant previously linked to familial moaning (p.Ile245Met). CONCLUSIONS: Our study provides insights into a poorly understood feature of PSP and highlights a troublesome symptom that is associated with substantial patient and caregiver burden. Further work is needed to investigate the pathophysiological basis of groaning and to develop effective therapies for it.