This study characterizes autonomic dysfunction in Progressive Supranuclear Palsy, assessing orthostatic hypotension, urinary dysfunction, and other autonomic features.
Autonomic dysfunction is a well-recognized but often underappreciated feature of Progressive Supranuclear Palsy that contributes substantially to patient morbidity and reduced quality of life[1]. Unlike the characteristic motor symptoms that define PSP, autonomic manifestations can appear early in the disease course and may provide valuable diagnostic clues as well as therapeutic targets.
The autonomic nervous system regulates involuntary bodily functions through its sympathetic and parasympathetic divisions. In PSP, neurodegeneration affects brainstem and subcortical structures that coordinate autonomic function, leading to dysregulation across multiple organ systems[2].
Cardiovascular Dysregulation: Orthostatic hypotension (a sudden drop in blood pressure upon standing) is one of the most common autonomic manifestations in PSP. Unlike Parkinson's disease where orthostatic hypotension often reflects peripheral autonomic neuropathy, in PSP it results from central autonomic failure related to brainstem involvement[3].
Urinary Dysfunction: Lower urinary tract symptoms are nearly universal in PSP, including urgency, frequency, nocturia, and often urge incontinence. These symptoms reflect loss of inhibitory control over the micturition reflex, which is mediated by brainstem structures damaged in PSP[4].
Gastrointestinal Dysmotility: Constipation is extremely common and often precedes motor symptoms by years. Delayed gastric emptying and reduced gut motility result from autonomic dysregulation. Some studies suggest that constipation may be a prodromal marker of PSP[5].
Thermoregulatory Dysfunction: Impaired sweating and temperature regulation occur due to sympathetic nervous system involvement. Patients may experience episodes of hypothermia or hyperthermia without appropriate physiological responses.
Autonomic testing may aid in the differential diagnosis of atypical parkinsonism:
Understanding autonomic dysfunction in PSP has important treatment implications:
Quantify Autonomic Dysfunction Severity: Characterize the spectrum and severity of autonomic dysfunction in PSP using standardized testing protocols.
Correlate with Disease Stage: Establish relationships between autonomic dysfunction severity and disease stage, duration, and progression rate.
Identify Diagnostic Biomarkers: Evaluate whether autonomic measures can serve as diagnostic biomarkers or improve diagnostic accuracy for PSP.
Assess Treatment Response: Establish whether autonomic measures can serve as sensitive endpoints for therapeutic interventions.
This is a cross-sectional observational study that evaluates autonomic function in patients with PSP and corticobasal syndrome. Each participant undergoes a single comprehensive autonomic evaluation visit.
The comprehensive assessment is conducted in a single visit lasting approximately 3-4 hours, including:
The head-up tilt table test is the gold standard for evaluating orthostatic intolerance and is central to this study[6]:
Procedure: After a resting period in the supine position, the table tilts to 70 degrees for up to 30 minutes while continuous monitoring of heart rate and blood pressure occurs.
Measurements:
Diagnostic Criteria:
Heart rate variability provides a non-invasive window into autonomic function:
Time-Domain Measures:
Frequency-Domain Measures:
Testing Protocol: 5-minute ECG recording during supine rest, followed by assessment of heart rate variability response to standardized breathing (6 breaths/minute).
Questionnaires:
Voiding Diary: 3-day voiding diary recording timing, volume, and episodes of incontinence
Based on clinical indication, additional testing may include:
The study aims to enroll approximately 75 participants with PSP and 25 with CBS. This sample size provides:
Findings from this study will inform:
Autonomic measures may serve as:
Autonomic dysfunction provides insight into:
Low DA, et al. Autonomic dysfunction in progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. 2015. ↩︎
Palma JA, et al. Orthostatic hypotension in neurodegenerative diseases: beyond orthostatic hypotension. Clin Auton Res. 2020. ↩︎
Sakakibara R, et al. Urinary dysfunction in progressive supranuclear palsy compared with other parkinsonian syndromes. J Neurol Sci. 2016. ↩︎
Abbott RD, et al. Frequency of bowel movements and future risk of Parkinson's disease. Neurology. 2001. ↩︎
Freeman R, et al. Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Clin Auton Res. 2011. ↩︎