Three hertz orthostatic tremor as "red flag sign" candidate for multiple system atrophy.

Aim: This study investigates the potential of 3-Hz orthostatic tremor (OT) as a diagnostic red-flag sign for differentiating multiple system atrophy (MSA) from Parkinson's disease (PD).

Patients and methods: A total of 615 PD patients and 234 MSA patients (120 MSA-P and 114 MSA-C) participated. OT at ~ 3 Hz and other frequencies was identified through rhythmic postural sway on the stabilogram map and confirmed by fast Fourier transform (FFT) analysis. Extensive assessment of OT occurrence, preferential stance conditions, sway direction, frequency spectrum, and intensity was performed and compared between the two diseases.

Results: Significant differences in OT features were observed. In PD, 104 patients (16.9%) exhibited tremors, mainly on a firm platform (79.8%), and preferentially in the medial-lateral direction (59.6%). About 40% of PD-related OT showed double peaks in the FFT map, with a frequency spectrum from 3.3 to 12.4 Hz. MSA tremors were observed in 133 patients (56.8%, including 46 MSA-P and 87 MSA-C patients), occurring after proprioceptive sensory input deprivation (94.7%). OT in MSA occurred exclusively in the anterior-posterior direction (100%), with no sub- or ultra-harmonics in the FFT map. Binominal logistic regression analyses demonstrated that frequency and stance conditions independently contributed to differentiating PD- and MSA-related OT. The 3-Hz tremor exhibited a sensitivity of 0.568, perfect specificity (1), an approximate negative predictive value of 0.8592, and a positive predictive value of 1 for MSA identification.

Conclusions: This study establishes the 3-Hz orthostatic tremor as a promising red flag sign for MSA identification.