Ting Qing Lim, Lu Yian Tan, Yi Xuan Tee, Darren Wan Pin Lim, Kelly Kher Nie Chen, Kai Shi Lim, Anis Nadhirah Khairul Anuar, Yuan Ye Beh, Kah Hui Yap, Yi Zhe Lim, Jeremy Christopher Fernandiz, Emilie Sing Yee Wong, Jeffrey Wei Yang Tee, Andrew Leslie Lee, Jun Ping Chua, University of Malaya PSP Study Group, Azlina Ahmad-Annuar, Tzi Shin Toh, Yi Wen Tay, Pin-Shiuan Chen, Adeline Su Lyn Ng, Yi Jayne Tan, Eng King Tan, Chin-Hsien Lin, Christos Ganos, Ai Huey Tan, Shen-Yang Lim
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.
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.