The aim of this study was to summarize the efficacy of DBS in PSP patients through analyzing related articles. To our knowledge, this is the first meta-analysis of DBS for PSP despite the fact that we were only able to combine results from 13 studies. In most cases, the scores of UPDRS Ⅲ decreased under DBS-ON conditions compared to those under DBS-OFF conditions, however, we found no statistical significances. Subgroup analyses indicated that the durations of follow-up time might influence the degree of clinical scales improvement while the phenotypes of PSP and target sites of PPN-DBS made little effects. We further found DBS were associated with sleep, AEO and cognitive functions of PSP patients, in addition to improving axial symptoms like falls and gait disorders.
PPN is a new target of DBS, and several studies have supported the positive effects of PPN-DBS for PD [14, 18, 45]. Garcia-Rill et al. further concluded some possible mechanisms of how stimulation in the PPN area could improve gait , which mainly results from the complex anatomy and multiple projections of PPN. There are evidences that position of the electrodes could lead to the variability of clinical response , which to some extent, can explain why our result was highly heterogeneous. Furthermore, pathological study observed that cholinergic and noncholinergic neuronal populations in the PPN were more affected in the PSP than in the PD patients  and this discovery helps us to understand why the efficacy of PPN-DBS was less obvious in this meta-analysis compared to studies focusing on PD patients. Therefore, in order to optimize the curative effect of PPN-DBS for PSP, it’s important to further understand the anatomy of PPN and improve the localization of the optimal targets.
The treatment of PSP is changeling since currently, no effective symptomatic or neuroprotective treatment is available for PSP . DBS is a promising tool for treatment of PSP. Galazky et al. proposed that bilateral PPN-DBS resulted in frequency-dependent effects in PSP patients and they observed low frequency improved cyclic gait parameters while high frequency ameliorated hypokinesia , which indicates that choosing proper stimulator parameters for individualized patients is essential. One PSP case treated by double implanted GPiPPN gained better clinical outcomes . Considering that basal ganglia and brainstem are generally affected in PSP patients , there may be an increased synergic effect existing when simultaneously stimulating different nucleus if the patient is tolerant.
Our meta-analysis has several limitations. The major limitation is the relatively small number of included studies as well as the small size of eligible participants. Second, some of included studies are case reports and the data from several studies are incomplete, which gains the bias of statistical outcomes though we combined some data from case reports to avoid unavailability. Moreover, it’s an important limitation to analyze the clinical scales which were performed in different cases where there were no consistent stimulation procedures, DBS parameters, and washout periods. Finally, the outcome of our study is simple though UPDRS Ⅲ as the primary outcome was well analyzed, we really desire more motor and non-motor scales to evaluate the DBS for PSP. Thus, further well-designed researches with larger cohorts are well needed.