Meta-analysis for the occurrence proportion of headache postoperatively.
A total of 619, 735 and 47 studies were retrieved through PubMed, EMBASE and Cochrane library, respectively. As shown in Fig. 1A, 18 studies with 4442 participants were finally included in meta-analysis. Information on the number of headaches was shown in Fig. 1B. Collectively, the pooled occurrence proportion were 29% (95% confidential interval: 20-38%) (Fig. 1C).
Dynamic analysis for the risk factors of pre-and post-operative headache.
Basic clinical and pathological characteristics of patients.
The baseline clinical characteristics of patients with pituitary adenomas are shown in Table 1. A total of 101 patients were enrolled for the present study, with a mean age of 45.71 ± 11.90 years. The mean maximum diameter of the tumor was 28.25 ± 11.04 mm. Thirty-nine patients (38.6%) were with tumor of Knosp’s grade 3-4, and 6 patients had those in Hardy’s Grade C-D. Gross total resection was achieved in 85 patients (84.2%). Twenty-four cases (23.8%) were functioning pituitary adenomas, and 15 cases of them were growth hormone secreting adenomas. There were 24 samples (23.8%) with positive staining of transcription factor TBX19. The average value of Ki-67 index was 2.56 ± 1.64%. Preoperatively, 32 patients were found to have slight sinusitis, based on head MRI. At the follow-up at 1 and 3-month postoperatively, 54 (53.5%) and 17 (15.9%) were confirmed to have sinusitis.
A total of 26 patients (25.7%) and 22 patients (21.8%) with HIT-6 score > 55 preoperatively and 1 month postoperatively, respectively. Only 6 patients remained with headache 3 months postoperatively. By using c2 test, tumor apoplexy was significantly associated with preoperative headache (Table 2), and Hardy’s Grade C-D was significantly associated with both preoperative and 1-month postoperative headache (Table 1). Additionally, postoperative sinusitis and clival osseous destruction were also significantly associated with headache 1month postoperatively (Fig. 2A).
Preoperative headache was significantly relived 3-month after operation.
HIT-6 scores of pre-and post-operations are compared in Fig. 2B. On the whole, the HIT-6 scores of 3 months postoperatively was significantly lower than the preoperative one (41.12 ± 0.72 vs. 46.06 ± 1.06, P= 0.0002) and the 1-month postoperative one (41.12 ± 0.72 vs. 46.82 ± 0.90, P< 0.0001). However, there is no statistically significant difference between preoperative HIT-6 scores and the 1-month postoperative one. These data suggested that patients with headache preoperatively could be significantly relived 3-month after operation.
Univariate and multivariate analysis of risk factors associated with headache post EES for PAs.
To compare the pattern of risk factors of pre- and post-operative headache, we first made the analysis on the preoperative HIT-6 scores. Univariate and multivariate analysis showed that both pituitary apoplexy (OR=3.59, 95%CI 1.22-10.58, p=0.020) and Hardy's grade C-D (OR=21.06, 95%CI 2.25-197.02, p=0.008) were independently risk factors (Table 3). However, there was no statistically significant difference in gender, presence of sinusitis, clival osseous destruction and Knosp’s grade, as well as growth hormone secreting adenomas and TBX19 positive (Table 3).
Then, we analyzed the risk factors associated with the headache 1 month postoperatively. Intriguingly, the pattern of risk factors is different from the preoperative one. As displays in Table 4, Hardy’s grade C-D (OR=10.53, 95%CI 1.02-109.19, P=0.049) remains an independent risk factor of postoperative headache. However, postoperative sinusitis (OR=3.88, 95% CI 1.16-13.03, P=0.028) also independently predicts the presence of postoperative headache at 1 month, which strongly recommends the prevention of sinusitis after EES for PAs.
Correlation analysis of sinusitis and headache in the subgroup of patients with headache.
Considering the clinical significance of the causal correlation between sinusitis and headache, we further analyzed their potential correlation in the subgroup of patients with headache. A total of 35 patients suffered from headache in the current study, including 26 preoperative and 9 postoperative ones. The dynamic change of HIT-6 scores and relevant presence of sinusitis were present in Fig. 2C-E.
Then, we further tracked the status of patients 3 months after operation, which are displayed in Fig. 3. Among the 26 patients with headache preoperatively, 12 patients relieved and 14 patients remain with headache 1-month postoperatively. The proportion of sinusitis was significantly higher in the headache group than the one in non-headache group (85.7% vs. 41.7%, p=0.038). At 3 months, 10 of the 14 patients relieved and 4 patients remain with headache. The proportion of sinusitis was tended to be higher in the headache group than the one in non-headache group (100% vs. 30.0%, p=0.070).
In the 9 patients who did not have headache preoperatively, 8 patients developed headache 1 month postoperatively, and 6 (85.7%) of them had sinusitis. The patient developed headache at 3 months also was also with sinusitis confirmed by MR. Collectively, these data strongly suggested that postoperative sinusitis partly accounts for the presence and relief of chronic headache following EES for PAs.