Significance: Cerebral oxygenation changes in the superior, middle, and medial gyri were used to elucidate spatial impairments of autonomic hemodynamic recovery during the head-up tilt table test (HUTT) in Parkinson’s disease (PD) patients with orthostatic intolerance (OI) symptoms.
Aim: To analyze dynamic oxygenation changes during the HUTT and classify PD patients with OI symptoms using clinical and oxygenation features.
Approach: Thirty-nine PD patients with OI symptoms [10: orthostatic hypotension (PD-OH); 29: normal HUTT results (PD-NOR)] and seven healthy controls (HCs) were recruited. Prefrontal oxyhemoglobin (HbO) changes during the HUTT were reconstructed with diffuse optical tomography and segmented using the automated anatomical labeling system. Decision trees were used for classification.
Results: HCs and PD-NOR patients with positive rates of HbO change (PD-POS) showed the greatest HbO recovery in the superior frontal gyrus (SFG) during tilt. PD-OH and PD-NOR patients with negative rates of HbO change (PD-NEG) showed asymmetric reoxygenation. The classification accuracy was 89.4% for PD-POS versus PD-NEG, 71% for PD-NOR versus PD-OH, and 55.8% for PD-POS versus PD-NEG versus PD-OH. The oxygenation features were more discriminative than the clinical features.
Conclusions: PD-OH showed decreased right SFG function, which may be associated with impaired compensatory autonomic responses to orthostatic stress.
Significance: Monitoring of cerebral perfusion rather than blood pressure changes during a head-up tilt test (HUTT) is proposed to understand the pathophysiological effect of orthostatic intolerance (OI), including orthostatic hypotension (OH), in Parkinson’s disease (PD) patients.
Aim: We aim to characterize and distinguish the cerebral perfusion response to a HUTT for healthy controls (HCs) and PD patients with OI symptoms.
Approach: Thirty-nine PD patients with OI symptoms [10 PD patients with OH (PD-OH) and 29 PD patients with normal HUTT results (PD-NOR)], along with seven HCs participated. A 108-channel diffuse optical tomography (DOT) system was used to reconstruct prefrontal oxyhemoglobin (HbO), deoxyhemoglobin (Hb), and total hemoglobin (HbT) changes during dynamic tilt (from supine to 70-deg tilt) and static tilt (remained tilted at 70 deg).
Results: HCs showed rapid recovery of cerebral perfusion in the early stages of static tilt. PD-OH patients showed decreasing HbO and HbT during dynamic tilt, continuing into the static tilt period. The rate of HbO change from dynamic tilt to static tilt is the distinguishing feature between HCs and PD-OH patients. Accordingly, PD-NOR patients were subgrouped based on positive-rate and negative-rate of HbO change. PD patients with a negative rate of HbO change were more likely to report severe OI symptoms in the COMPASS questionnaire.
Conclusions: Our findings showcase the usability of DOT for sensitive detection and quantification of autonomic dysfunction in PD patients with OI symptoms, even those with normal HUTT results.
The Valsalva maneuver (VM) with beat-to-beat blood pressure and heart rate monitoring are used to evaluate orthostatic intolerance (OI). However, they lack the ability to detect cerebral hemodynamic changes, which may be a cause of OI symptoms. Therefore, we utilized near-infrared spectroscopy during VM. Patients with OI symptoms and normal healthy subjects were recruited. Patients were subgrouped according to VM results: patients with normal VM (NVM) and abnormal VM (AbVM). Oxyhemoglobin (HbO), deoxyhemoglobin, and total hemoglobin changes were measured at four different source–detector distances (SD) (15, 30, 36, and 45 mm), and latency, amplitude, duration, and integrated total signal were calculated. Those parameters were compared between a normal healthy control (HC) group and the two OI patient subgroups. We found that HbO increment latency at 30-mm SD in the HC, NVM, and AbVM groups was as follows: 0.39±0.23 s, 2.79±0.36 s, and 8.14±0.55 s, respectively (p<0.05). Among the four parameters we evaluated, latency of HbO increment was the best marker for differentiating OI.
In this work, we analyzed the clinical applicability of NIRS for use during Quantitative Autonomic Testing (QAT). QAT is a protocol consisting of deep breathing, Valsalva maneuver, and tilt table examination. It is used to diagnose a patient with disorders of the autonomic nervous system (ANS). Disorders of ANS includes orthostatic hyper/hypotension, vasovagal syncope, and postural orthostatic tachycardia syndrome. The results of QAT are typically analyzed with the use of blood pressure and heart rate data, however these metrics may be influenced by factors such as arrhythmia, making the data interpretation and diagnosis difficult for clinicians. We tested our custom built 108-channel NIRS probe on 26 elderly patients during the QAT protocol with various ANS disorders. We found that prefrontal cerebral oxygenation correlated well with blood pressure and heart rate changes for all three tasks, making it a clinically feasible tool for observing ANS functionality. During the Valsalva maneuver, we observed a longer delayed and lower amplitude response of cerebral oxygenation to the prefrontal area in orthostatic intolerant patients. During the tilt table examination, we saw a larger response in cerebral oxygenation and less equal transient cerebral oxygenation during tilt up and tilt down in tilt table examinations that were positive (unhealthy), compared to tilt table examinations that were negative (healthy). Overall, our study showcases NIRS as an enhanced tool for understanding ANS disorders.
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