Neurological Disorders

Markers of Parkinson’s Disease Progression Using Cerebrovascular, Autonomic and Small Fiber Polyneuropathy Features

Abstract

Daniela AP, Paula R, Arthur PH, Lan Q, Vera N and Peter N

Background: Reliable, quantitative progression markers for Parkinson’s disease (PD) are needed. We aimed to determine whether the quantitative analyses of the cerebrovascular, cardiovascular autonomic and small fiber polyneuropathy features correlate with PD severity. Methods: This was a single center, retrospective study. PD patients were evaluated using standardized cardiovascular autonomic reflex testing including deep breathing, Valsalva maneuver, tilt test and skin biopsies for the quantification of epidermal sensory and sweat gland sudomotor fibers. Parkinsonism severity was quantified by the Unified Parkinson’sDisease Rating Scale (UPDRS). Severity of non-motor symptoms was evaluated using QASAT (Quantitative scale for grading of cardiovascular reflex tests, QSART and small fibers densities from skin biopsies) adjusted for age and gender. Correlations were obtained using the Pearson’s correlation coefficient (r). Results: We tested 109 PD patients (age 70.14 ± 11.2, disease duration 4.8 ± 4.06 years). UPDRS-II was correlated with the following QASAT scores: total (r=0.62, p<0.0001), adrenergic function (r=0.71, p<0.001), sensory fiber analysis (epidermal nerve fiber density or ENFD, r=0.34, p<0.001), cerebral blood flow scores (r=0.43, p<0.007) and sudomotor function (r=0.42, p<0.0001). UPDRS-III correlated with the following QASAT scores: total (r=0.46, p<0.0017), adrenergic function (r=0.48, p<0.0001), ENFD (r=0.31, p<0.001) and sudomotor function (r=0.34, p<0.05). Conclusions: Autonomic, cerebrovascular and sensory abnormalities coexist in PD and they progress along with disease severity. The adrenergic score, that primarily measures the severity and duration of orthostatic hypotension during tilt test, had the best correlation with disease severity. QASAT may be a feasible instrument for the objective monitoring of PD progression presenting with autonomic nervous system involvement. These findings need to be validated in a prospective study.