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.