Quantitative Autonomic Function Test in Differentiation of Multiple System Atrophy from Idiopathic Parkinson Disease
Introduction
Idiopathic Parkinson disease (IPD) and multiple system atrophy-Parkinson type (MSA-P) are neurodegenerative disorders that share clinical features such as parkinsonism and autonomic dysfunction. However, differentiating between these two conditions is crucial for predicting treatment response and disease prognosis. MSA primarily involves the preganglionic pathway of the autonomic nervous system, leading to early and prominent autonomic dysfunction. In contrast, IPD mainly affects the postganglionic pathway, with autonomic dysfunction being less prominent in the early stages. Despite the importance of distinguishing between these conditions, existing studies have shown inconsistent results, and an effective diagnostic tool remains elusive. This study aimed to evaluate the utility of quantitative autonomic function tests (AFTs) in differentiating MSA-P from IPD, particularly in the early stages of the disease.
Methods
The study prospectively enrolled 36 patients with parkinsonism (22 with IPD and 14 with MSA-P) from Soonchunhyang University Bucheon Hospital between February 2014 and June 2015. All patients underwent comprehensive diagnostic evaluations, including brain magnetic resonance imaging (MRI) and [18F]N-(3-fluoropropyl)-2b-carbon ethoxy-3b-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography (PET). Additional tests, such as [18F]fluorodeoxyglucose (FDG) PET or metaiodobenzylguanidine (MIBG) scintigraphy, were performed selectively based on clinical findings. Patients with parkinsonism due to other causes, such as drug-induced parkinsonism, stroke, or structural brain disease, were excluded.
Autonomic function tests were conducted using the Finometer® Pro and quantitative sudomotor axon reflex test (QSART). The tests included heart rate response to deep breathing, Valsalva maneuver, and head-up tilt test (HUTT). Parasympathetic indexes measured were the expiratory/inspiratory (E:I) ratio, Valsalva ratio (VR), and vagal baroreflex sensitivity (BRSv). Sympathetic adrenergic indexes included pressure recovery time (PRT), adrenergic baroreflex sensitivity (BRSa), sympathetic index 1 (SI1), sympathetic index 3 (SI3), early phase II mean blood pressure (BP) drop, and pulse pressure reduction rate (PPR). Orthostatic hypotension (OH) was defined as a sustained reduction in systolic BP of at least 30 mmHg or diastolic BP of 15 mmHg during HUTT.
Functional status was assessed using the Unified Parkinson Disease Rating Scale (UPDRS), Unified Multiple System Atrophy Rating Scale (UMSARS), and Hoehn and Yahr (H&Y) scale. Statistical analyses were performed using IBM SPSS Statistics version 24.0, with a P value <0.05 considered statistically significant.
Results
The study included 22 patients with IPD and 14 patients with MSA-P. There were no significant differences in sex, age, or disease duration between the two groups. However, patients with MSA-P had slightly higher H&Y scores (P=0.045) and greater functional deficits, as indicated by higher UPDRS and UMSARS scores.
Among the autonomic function test results, PRT was significantly longer in patients with MSA-P compared to those with IPD (P=0.004). The area under the receiver operating characteristic curve for PRT was 0.713, with a cut-off value of 5.5 seconds (sensitivity, 71.4%; specificity, 72.7%). OH was more frequent in the MSA-P group (71.4%) than in the IPD group (36.4%). Total and adrenergic composite autonomic scoring scale (CASS) scores were also significantly higher in the MSA-P group (P=0.003 and P=0.004, respectively).
Correlation analysis revealed that BRSa (r=‒0.356, P=0.036) and VR (r=‒0.455, P=0.009) were significantly associated with UMSARS and H&Y scores, indicating that these indexes may reflect disease severity. However, no significant correlations were found between autonomic function indexes and UPDRS scores.
Discussion
This study demonstrated that quantitative autonomic function tests, particularly PRT, can be useful in differentiating MSA-P from IPD in the early stages of the disease. The prolonged PRT in MSA-P patients suggests more severe sympathetic dysfunction compared to IPD. Additionally, the presence of OH was more common in MSA-P, although it was also observed in a significant proportion of IPD patients, limiting its diagnostic utility alone.
The significant correlations between BRSa, VR, and functional status scales (UMSARS and H&Y) highlight the potential of these indexes as markers of disease severity. However, the lack of correlation with UPDRS scores suggests that autonomic dysfunction may not directly reflect motor symptom severity in IPD.
This study has several limitations. First, the diagnosis of IPD and MSA-P was based on clinical criteria and neuroimaging rather than histopathological confirmation. Second, the effects of anti-Parkinson medications on autonomic function were not fully controlled, although patients did not take these medications on the day of testing. Third, the relatively small sample size and the inclusion of patients with H&Y scores ≤3 may limit the generalizability of the findings.
Future studies with larger cohorts, longer follow-up periods, and pathological confirmation are needed to validate these findings and explore the potential of AFTs as biomarkers in the differential diagnosis of parkinsonian disorders.
Conclusion
In conclusion, the quantitative autonomic function test, particularly PRT, is a valuable tool for differentiating MSA-P from IPD in the early stages of the disease. The significant correlations between BRSa, VR, and functional status scales further underscore the utility of these indexes in assessing disease severity. These findings contribute to the growing body of evidence supporting the use of AFTs in the clinical evaluation of patients with parkinsonism and autonomic dysfunction.
doi.org/10.1097/CM9.0000000000000359
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