Study selection and characteristics
The whole procedure of study selection was presented in Fig. 1. Based on an comprehensive combination of search keywords, we screened a number of 36 papers by articles’ title and abstract, 6 of them [11–16] were picked up as they fulfilled all inclusion criteria with intact data, strict experiment design to minor publication bias in this meta-analysis. All the enrolled studies were well-controlled and meeting selection criterions. Then according to the sample size, applied frequency, width of DBS, enrolled patients of all the studies were classified to different subgroups. Groups were also divided based on pre-SST and post-SST scores as well as UPDRS-III scores (on/off modulation). Overall, 6 studies constituting 326 patients were evaluated with SST scores, UPDRS, sample size, gender, age, frequency and width of stimulation.
Study characteristics and quality assessment
The enrolled studies and detailed clinical characteristics are exhibited in Table 1. Three studies contained more than 50 patients while the other two studies had relatively smaller sample size. Two studies use relatively low stimulation frequency and three studies used higher frequency. Three articles used shorter pulse width (mean < 60us) and others used longer index. The publication time of all papers ranged from 2004 to 2019. The number of patients enrolled ranged from 22 to 78. To evaluate the quality of related studies and patients’ data, Newcastle-Ottawa Quality Assessment scores (NOS) were conducted and scores varied from 6 to 9 (information presented in Table 2), which indicated that the quality of enrolled studies was high. Exacted clinical data could be browsed in Tables 1, 2.
Characteristics of included studies into meta-analysis
Newcastle-Ottawa Quality Assessment Scale of included studies
Association between DBS in Parkinson patients and olfactory function
Methods described in previous section were used to evaluate the results, the association between DBS and olfactory function were assessed by forest plots. First data (Fig. 2.A) showed that all the enrolled Parkinson patients had effective DBS with improved UPDRSIII scores after the operation (P < 0.0001).Then the relationship between DBS and olfactory function was observed, and results showed DBS had clearly positive effect on olfactory function in Parkinson patients (P < 0.0001) (Fig. 2.B). Following funnel plots showed the heterogeneity of these groups is acceptable, the P value and I2 of this results showed they were eligible. Heterogeneities existed among different groups of UPDRS scores improvement which would be discussed in following section (Heterogeneity: Chi² = 132.9, df = 5 (P < 0.0001, I² = 96%). No notable heterogeneities were observed among these studies (Heterogeneity: Chi² = 9.39, df = 5 (P = 0.27; I² = 5%) (Fig. 2.D). Thus the result was reliable to support our conclusion and random-effect model was introduced to evaluate the possible publication bias to further confirm the hypothesis and explore clinical characters.
Association between clinic pathological features and olfactory function improvement
To further confirm the potential effect of DBS in olfactory function, the relationship between Parkinson patients’ olfactory function and clinic pathological patterns including disease duration, education level, gender and average age were explored precisely. As seen in Table 2 and Figs. 3, forest plots of 6 eligible studies showed the DBS was associated with Parkinson patients olfactory function improvement (P < 0.0001). No great changes of olfactory function scores was found between different gender group (P = 0.06) or education level (P = 0.97) (Fig. 3.A, B), but in age group, it seems that age structure effected improve rates rate (P = 0.02) (Fig. 3.C). The difference may originate from the different morbidity and self-healing ability in different age and the criteria for young (< 60) and old (> 60) do have influence on the bias (P = 0.006).
Sensitivity and subgroup analyses
Subgroup analysis was also performed on sample sizes and stimulation parameters such as stimulation frequency and stimulation width to explore the potential sources of heterogeneity. Table 3 and Fig. 4 present the results of subgroup analyze on relationship between Parkinson patients’ olfactory function and stimulation parameters. These results also indicated that sample size (P = 0.38, Fig. 4A) and as well as stimulation width (P = 0. 08, Fig. 4B) did not obviously effect the olfactory function improvement. However stimulation frequency (P = 0. 002, Fig. 4C) influenced the heterogeneity of the study. However,
Data of subgroup for analyze of sample size and stimulation paramaters effects
Potential publication bias was evaluated by using Begg’s funnel plot and Egger’s test. Final results were shown in Fig. 5A, B, C. The results manifested that there were no obvious publication bias existing in enrolled studies, and no evidence of significant publication bias were found in this paper.
As seen in Fig. 5A, B, C and Table 3 group size didn’t effect Olfactory improvement after DBS operation (Test for subgroup differences: Chi² = 1.79, P = 0.18, I² = 44.3%). However, the heterogeneity of UPDRS III scores existed in these subgroups (Heterogeneity: Chi² = 132.99, P < 0.0001; I² = 96%), which may come from the different diagnose patterns of PD in different countries. Additionally, stimulation parameters didn’t influence the conclusion. And there were little heterogeneity among these subgroups (Frequency high vs low: Chi² = 15.59 P = 0.06, I² = 64%; Width long vs short: Heterogeneity: Chi² = 15.59 P = 0.008, I² = 68%).With these results, the heterogeneity of tumor grades mainly resulted from the UPDRS III scores.
DBS effects on Olfactory function sensitivity and specificity
Sensitivity and specificity analyses were also conducted to find the diagnostic effect of olfactory scores in PD patients. As seen in Figs. 6, forest plot and SROC curve of 5 eligible studies showed the higher olfactory scores is highly related to lower UPDRSIII of DBS which means improvement in PD patients and indicate good potential of sensitivity and specificity to define therapeutic effect which is in coincide with our theory.