Hypoperfusion in Supramarginal and Orbital Gyrus, Position Discrimination Test, and Microsaccades as a Predictor of Pisa Syndrome in Parkinson's Disease

Abstract

Patients with Parkinson's disease (PD) experience significantly reduced quality of life when PD is complicated with Pisa syndrome (PS). PS is a postural abnormality associated with a lateral bending of the trunk, causing the patient to lean to one side. Microsaccades during fixation are transmitted to the visual cortex, and this gaze movement may be impaired in PD. We aimed to detect presymptomatic signs of PS. We enrolled 50 patients with PD without dementia and investigated the visual systems in patients with concurrent PD and PS based on a Romberg ratio of<1.0. Gaze analysis, pupil diameter, stabilization tests, neuropsychological tests, and cerebral perfusion scintigraphy were reviewed and statistically analyzed. Two years later, we divided the patients into three groups as follows: PISA++ (patients who had PS at enrollment), PISA-+ (patients without PS that developed PS during the 2-year period), and PISA-- (patients without PS that did not develop PS during the 2-year period). The PISA-+ group exhibited a significantly higher daily levodopa dose and longer fixations, as well as lower position discrimination, Wechsler Adult Intelligence Scale-Third Edition blocking, and blood flow in the left supramarginal and orbital gyri than that in the PISA-- group. The PISA++ group showed a significantly longer fixation time and lower Mini-Mental State Examination score, Romberg ratio of area, amplitude, velocity of microsaccades, and blood flow in the left precuneus and cuneus than that in the PISA-+ group. Before the onset of PS, hypoperfusion occurred in the correlative visual cortex and the position discrimination test. Patients with PS have reduced saccades and slow microsaccades.

Figure 1

Decision tree model to optimize the PISA+ using the clinical findings at enrollment. The combination of disease duration >6 years and length during eye opening (gravicorder) >95 cm resulted in PISA+. A combination of disease duration <6 years and position discrimination test score <18 points resulted in PISA+.

Figure 2

¹²³I-IMP single-photon emission computed tomography (SPECT) findings of the three groups. 3DSSP was used to compare hypoperfusion among the three groups. The SPECT images from the participants were spatially transformed into a Talairach Atlas. Significant differences were defined by Z scores ≥2.5. PISA-+ vs. PISA-- shows hypoperfusion in the left supramarginal and orbital gyri. PISA++ vs. PISA-+ shows hypoperfusion in the left precuneus, cuneus, and superior temporal gyrus. PISA++ vs. PISA-- shows hypoperfusion in the left precuneus and cuneus.

Figure 3

Clinical model of Pisa syndrome in patients with Parkinson's disease. In the stage of preclinical Pisa syndrome, perfusion of the frontal orbital gyrus and supramarginal area and position discrimination score were decreased. In Pisa syndrome, perfusion of the precuneus and cuneus was decreased, and the Romberg rate of the area was <1.0. The amplitude and velocity of microsaccades were decreased in Pisa syndrome. SPECT, single-photon emission computed tomography.