Clinical characteristics and long-term outcome in patients with Rathke’s cleft cysts associated with headache

Clinical characteristics and long-term outcome in patients with Rathke’s cleft cysts associated with headache | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical characteristics and long-term outcome in patients with Rathke’s cleft cysts associated with headache Yasuo Sasagawa, Riho Nakajima, Toshiya Ichinose, Ryoken Kimura, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7747251/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 09 Feb, 2026 Read the published version in Neurosurgical Review → Version 1 posted 13 You are reading this latest preprint version Abstract Objective This study aimed to investigate the clinical features and long-term outcomes of patients with Rathke’s cleft cysts (RCCs) presenting with headaches. Methods A retrospective analysis was conducted on 51 patients who underwent transsphenoidal surgery for RCCs between 2009 and 2022. Patients were divided into headache (n = 27) and non-headache (n = 24) groups. Clinical data, MRI findings, and surgical outcomes were analyzed. Headache improvement was assessed using a 5-point postoperative scale. Results Patients in the headache group were significantly younger (40 vs 48 year: p < 0.05), had less visual disturbance (7% vs 63%: p < 0.01) and had smaller cysts (10 mm vs 17 mm: p < 0.01). MRI showed a higher prevalence of T1 hyper intense (74% vs 46%: p < 0.05) and intracystic nodules (62% vs 25%: p < 0.05) in the headache group. Multivariate analysis identified less visual disturbance (p < 0.01) and smaller cyst (p < 0.01) as independent predictors of headache presence. Postoperative follow-up (mean: 5.3 years) revealed that 66% of patients experienced headache resolution or improvement, while 34% reported persistent or recurrent symptoms. Resolution or improvement after surgery correlated with less frequent use of analgesics and specific headache characteristics (frontal/retro-orbital location). Conclusion In patients with RCCs, larger cyst size does not necessarily correlate with the presence of headache, indicating that factors such as inflammation may contribute to symptom development. Surgical intervention offers sustained relief in many cases, though long-term outcomes vary. Further research is needed to clarify mechanisms and optimize treatment strategies. Rathke’s cleft cyst headache transsphenoidal surgery MRI Figures Figure 1 Figure 2 Introduction Rathke’s cleft cysts (RCCs) are benign cystic lesions that occur in the sella turcica and suprasellar region. RCCs are generally asymptomatic and are detected incidentally on imaging studies associated with trauma or dizziness etc. 1) However, RCCs are sometimes symptomatic, presenting with visual dysfunction, endocrine disturbances, and headaches. 2) Visual symptoms associated with RCCs are caused by cystic compression of the optic chiasm. Surgical drainage of cyst contents relieves pressure on the optic chiasm and improves visual symptoms. 3) With regard to endocrine disturbances in RCCs, it is reported that inflammation within the cysts as well as pressure of the cysts on the pituitary gland is involved. 6) Postoperative improvement in endocrine function has been reported to be worse than improvement in visual dysfunction. 4), 5) Although the mechanism of headache associated with RCCs is not clear, mass effect on dura, inflammation within the cyst, or secretion of the cyst contents into the subarachnoid space have been postulated. 7), 8) Postoperative improvement rates for headache associated with RCCs vary from 40–100%. 7), 9), 10), 11), 12), 13) It is speculated that these difference rates may be due to the short follow-up period and the fact that the patients may have had other headaches such as migraine or tension headaches. This study conducted the long-term outcome of headache in patients with RCCs more than three years after transsphenoidal surgery. In addition to the outcome of headache, these patients are compared to RCC patients without headache to clarify their characteristics. Methods Subjects The institutional review board approved this retrospective study (No. 2023 − 361) and waived the requirement to obtain informed consent. We retrospectively studied the records of all patients who were treated at Kanazawa University Hospital for a RCCs as an initial treatment between January 2010 and March 2022. Fifty-five patients were selected. Of these patients, thirty-one patients had episodes of headache within 3 months of the surgery, but 4 had an obvious cause for their headache. Two patients had hyponatremia, one had acute sinusitis and one had head trauma. These 4 patients were excluded from this study as headaches not associated with RCCs. As a result, 27 patients were assigned to RCCs with headache (headache group). Meanwhile, the remaining 24 patients were assigned as RCC patients without headache (non-headache group). MR Images Preoperative MR images of the pituitary region were obtained for all selected patients, using a 3-Tesla magnet strength scanner (MAGNETOM Trio, Siemens, Germany or Signa Excite HDx 3.0T, GE Healthcare, Japan) with a 32-channel head coil. Pre-enhanced T1-, T2-weighted, and post-enhanced T1-weighted images were taken for all patients in the sagittal and coronal planes with 1.5 mm slice thickness. In order to identify pituitary gland and cyst wall, dynamic T1-weighted fast spin echo sequences were also acquired during the injection of 10 cc gadolinium followed by 20 cc of normal saline at a standard rate of 3 cc/s. The maximum cyst size (diameter) was measured in the coronal plane on a T1-weighted post-enhanced image. Radiologic evaluation of cyst contents was undertaken as follows: signal intensities of cyst contents in both T1- and T2- weighted images. A small lesion that were very hypo intense within the cyst at T2 image were evaluated as “intra cystic nodule”, which are characteristic of RCCs. 17) Postoperative imaging evaluations were performed at 3 to 6 months. If there was no recurrence, a follow-up MRI was performed once a year. Cyst reaccumulation was defined as when the maximum diameter of the cyst on the last MRI was the same as the preoperative diameter. Endocrinological Evaluation Endocrinological status was examined both pre- and postoperatively and included determining levels of plasma growth hormone, prolactin, adrenocorticotropic hormone, cortisol, thyroid stimulating hormone, thyroid hormone (free T3 and T4), luteinizing hormone, and folliclestimulating hormone. Hyperprolactinemia was defined as elevated PRL above the normal range for sex. Urine volume and gravity were evaluated to diagnose diabetes insipidus. Surgical Procedures All patients were treated with endoscopic transsphenoidal operations. Surgery for RCCs was indicated when headaches were not controlled with painkillers and disturbed patients’ daily lives. Our surgical procedure for this series of RCCs is the standard one. After incision of the dura matter and cyst wall, the cyst content was drained out sufficiently and the cyst wall was resected partially for pathologic diagnosis. Sellar floor reconstruction was not performed unless cerebrospinal fluid (CSF) leakage was present. If a CSF leak was identified, repair was performed using an autologous subcutaneous fat graft from the abdomen to reconstruct the sellar dura. Postoperative Headache Survey Postoperative headache surveys were conducted at the time of annual follow-up MRI visits. As for patients who had lost their outpatient visits, we were interviewed by telephone. The outcome in headache was rated on a 5-point scale as follows; 1. Disappeared, 2. Improved, 3. Relapsed, 4. No change, 5. Worsened. In a subanalysis, patients with scale 1 and 2 were divided into the improvement group and patients with scale 3, 4, and 5 into the non-improvement group. Between these two groups, preoperative headache characteristics, cyst reaccumulation, use of analgesics and tranquilizers were examined. Flow chart of the participant inclusion process is shown in Fig. 1 . Statistical Analysis For statistical analysis, the patients were divided into headache and non-headache groups. Univariate analysis between the two groups was performed. The mean ± standard deviation and median are presented for parametric and nonparametric variables, respectively. The Mann–Whitney U test was used to compare continuous data (e.g., cyst size), and the Fisher’s exact test was used to compare categorical data (e.g., sex) between the 2 groups. Multivariate stepwise logistic regression analysis was performed to detect independent predictors of the RCC patients with headache using factors that had significant associations in univariate analysis. All data were analysed using the JMP Pro statistical analysis software version 16.2.0 (SAS Institute Japan Inc., Tokyo, Japan) and SPSS statistics 29.0.1.0. (IBM Japan Ltd., Tokyo, Japan). Statistical significance was set at a p-value of < 0.05. Results Patient Characterization The baseline characteristics of the patients with and without headache are shown in Table 1. Female accounted for 76% of the headache group and 65% of the non-headache group (P = 0.374). The headache group was significantly younger than the non-headache group (40.2 vs 48.3 years, P = 0.041). Significantly fewer patients in the headache group had visual dysfunction than in the non-headache group (7% vs 63%, P = 0.002). With regard to endocrinological disturbances, there were no significant differences between the two groups in mean hyperprolactinemia (16 vs 19 ng/ml P = 0.329) or in the percentage of hypopituitarism (7.4% vs 20.8%, P = 0.084). Comparison on MRI showed significantly smaller cysts in the headache group (10.1 vs 17.3 mm, P = 0.0017). In the evaluation of cyst content, high intense on T1-weighted images was significantly higher in the headache group than in the non-headache group (74% vs 46%, P = 0.021). Comparison of intracystic nodules on T2-weighted images also showed a significantly higher in the headache group (62% vs 25%, P = 0.013). Subsequently, the multiple regression analysis was performed. To identify the independent variables related to the headache, a stepwise analysis was carried out using the following items: female, age, visual disturbance, cyst size, T1 hyper intense and intracystic nodule. Visual disturbance and cyst size were the factors associated with the headache. These variables were used as the independent variable in the regression analysis. Visual disturbance (p = 0.0026) and cyst size (p = 0.0009) were significantly correlated with the headache. Postoperative Headache Survey Of the 27 patients in the headache group, 21 were able to be assessed for headache after surgery. The remaining six could not be interviewed because they could not be contacted. Sixteen of the 21 were interviewed during the annual follow-up MR image at clinic. The remaining 5 patients were interviewed by telephone because they had moved or other reasons. At the time of the survey, the mean time since surgery was 5.3 ( 3 – 12 ) years. The outcome for headache was classified into five categories, with the following results. 1. Disappeared: after surgery, headache completely disappeared in 5/21 patients (23%). 2. Improvement: although headaches improved compared to preoperatively, 9/21 (43%) of the patients reported that they still had headaches. 3. Relapsed: five (24%) patients experienced headache resolution immediately after surgery, but it recurred and remained as severe as before surgery. 4. No change: two patients (10%) had no improvement in headache after surgery. 5. Worsened: no patient's headache was worse than preoperatively. As a subanalysis, categories 1 and 2 were defined as headache improvement group, and the 3, 4, and 5 were defined as non-improvement group. Clinical characteristics were compared between the improved and non-improved groups (Table 2). Half of the patients in the improved headache group complained of episodic headache (occurring in sudden, intermittent episodes) before surgery, although not significantly different than those in the non-improvement group (50% vs 14%, P = 0.112). Regarding the location of the headache, the frontal region and/or behind the eyes was significantly more common in the headache group (64% vs 14%, P = 0.031). Other sites in the improved group included the temporal region in 21%, the whole head in 15%. Cyst size on preoperative MRI was similar in the improved and non-improved groups (10.1 vs 10.2 mm, P = 0.366). Regarding cyst contents, T1 high intense findings were comparable in both groups (93% vs 71%, P = 0.185). In intracystic nodules, there was no significant difference, although there were more frequently in the improved group (71% vs 29%, P = 0.061). Significantly fewer patients in the improvement group were taking analgesics and/or tranquilizers at the time of the survey (14% vs 85%, P = 0.001). Postoperatively, there was one case each in the improvement and non-improvement groups that presented cyst reaccumulation on MRI (7% vs 14%, P = 0.599). The one of the patients underwent reoperation due to relapse headache and reaccumuration of the cyst. The headache disappeared again, after the second surgery (Illustrative case). Illustrative Case A 29-year-old woman experienced a sudden headache behind her eyes. The pain persisted the next day, so she visited the outpatient clinic. A head CT scan revealed a high-density mass in the sella turcica. MRI showed a cyst with high signal intense on T1 weighted image and high signal intense with intracystic nodule on T2 weighted image, with no contrast enhancement within the cyst (Fig. 2 A-C). She was referred to our hospital, and we diagnosed the mass as a RCC. She had been taking painkillers for about one month, but they were ineffective. She returned to our hospital and surgery was planned. Baseline serum pituitary hormone levels, excluding prolactin (28 ng/ml), were within the normal range. Endoscopic transnasal transsphenoid surgery was performed. Clear and viscous cystic fluid was drained. The specimen contained ciliated epithelial cells, confirming the diagnosis of RCC. The headaches completely resolved postoperatively. Follow-up MRI were performed four times over a three-year period, and no cyst recurrence was observed (Fig. 2 D). Five years after the surgery, she experienced a recurrence of headaches and visited our hospital. The cyst had refilled to the same size as before the surgery (Fig. 2 E). A second surgery was performed, and the cyst contents were drained again. To prevent cerebrospinal fluid leakage, abdominal fat was grafted into the sella turcica during surgery. The headache has completely resolved, and one year have passed since the second surgery. There has been no recurrence of headache, reaccumulation of the cyst (Fig. 2 F) and pituitary dysfunction. Discussion This study analysed the clinical characteristics, imaging features, and long-term outcomes in patients with RCCs, focusing particularly on those with associated headaches. Several key findings emerge from this investigation, offering insights into the relationship between RCCs and headache symptoms, as well as the efficacy of surgical intervention. Pathophysiology of Headaches in RCCs and Imaging Features Patients with RCC-associated headaches were found to have distinct clinical and radiological features compared to those without headaches in this study. Headaches were more prevalent in younger patients and those with smaller cyst sizes, suggesting that factors other than cyst compression, such as inflammation or secretion of cyst contents, may play a critical role in symptom generation. The presence of T1 hyper intense signal and intracystic nodules on MRI were significantly associated with the headache group in univariate analysis, consistent with previous studies indicating that these features might reflect inflammatory processes or biochemical irritants contributing to headache pathophysiology. 7), 8), 17) Interestingly, multivariate analysis also showed that no visual impairment or small cysts were associated with headaches. These results may be important in considering the mechanism of headache in RCCs. One possibility is that cyst fluid periodically leaks into the subarachnoid space, causing headaches and keeping the cyst small. Therefore, headaches occur without the cyst compressing the optic chiasm. Previous reports have also noted spontaneous regression of RCC in patients with severe headache, suggesting rupture of the cyst into the subarachnoid space. 20), 21), 22) Such imaging biomarkers could be helpful in identifying patients at higher risk for headaches and tailoring their treatment strategies. Further investigations using advanced imaging and biochemical analyses of cystic contents may help elucidate these mechanisms. Postoperative Outcomes Surgical intervention via transsphenoidal surgery demonstrated variable success in resolving headaches. The improvement rate of postoperative headache in RCCs in previous publications is quite high, ranging from 75–94%. 7), 10), 12), 15) 17) 18) In our study, 66% of patients experienced either complete resolution or improvement in symptoms. We speculate that the reason for the lower rate of headache improvement compared to previous papers is the difference in the timing of headache evaluation. In most of the previous papers, the timing of headache evaluation was undocumented, probably because the evaluation was performed immediately after surgery or several months after surgery. On the other hand, our paper analyzes the long-term outcome of headaches, with the average time of headache assessment being approximately 5 years post-surgery. In any case, these improvement rates highlight the potential efficacy of surgical drainage in alleviating headache-related discomfort. However, the persistence or recurrence of headaches in a subset of patients underscores the multifactorial nature of these symptoms, which may also be influenced by pre-existing headache disorders, such as migraines or tension-type headaches. 8), 9) Improved headache outcomes were associated with fewer postoperative requirements for analgesics or tranquilizers, indicating that surgical intervention might also reduce the reliance on symptomatic medication. These findings support the consideration of surgery as a viable option for symptom relief in appropriately selected patients. As for predictors of surgical success, preoperative headache characteristics, such as episodic patterns and specific locations (e.g., frontal or retro-orbital areas), appeared to influence outcomes. Patients with episodic headaches had better postoperative outcomes, suggesting that headache subtype and localization may guide surgical decision-making. 7),8) Limitations and Future Directions This study is limited by its retrospective design, single-center setting, and reliance on subjective headache assessments. Future prospective studies with larger sample sizes and objective headache scoring systems are needed to validate these findings. In addition, since data on preoperative headache history (migraine, etc.) is not available, there is a possibility of confusion with primary headache. Additionally, incorporating biochemical analyses of cyst contents and advanced imaging modalities could provide deeper insights into the mechanisms underlying RCC-associated headaches. Exploring adjunctive therapies such as targeted anti-inflammatory treatment may also contribute to improving headaches in RCC. Conclusion This study highlights the clinical significance of headaches in RCC patients and identifies key imaging and clinical predictors of their occurrence. While transsphenoidal surgery is effective for many, its success in resolving headaches varies, reflecting the complexity of their pathophysiology. Further research is necessary to improve the diagnostic and therapeutic approaches for RCC-associated headaches, ultimately enhancing patient care and quality of life. Declarations Ethical approval : This study was approved by the Ethics Committee of Kanazawa University Hospital (Approval No. 2023 − 361). All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional or national research committee and with either the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. For this type of study, formal consent was not required. Consent for publication : All authors agreed for the publication. Consent to participate : All authors agreed to participate in this study. Conflicts of interest : The authors declare that they have no conflicts of interest. Clinical trial number Not applicable. Author Contribution "Y.S. wrote the main manuscript text. T.I. prepared figures. R.K., S.T. and M. O. collected the clinical data. R.N. performed statistical processing. M.N. revised the manuscript. All authors reviewed the manuscript." Acknowledgments: No specific funding was provided for this work. Data Availability Data and pictures shown in the manuscript will be available on demand. References Culver SA, Grober Y, Ornan DA, Patrie JT, Oldfield EH, Jane JA Jr, Thorner MO (2015) A Case for Conservative Management: Characterizing the Natural History of Radiographically Diagnosed Rathke Cleft Cysts. J Clin Endocrinol Metab 100(10):3943–3948 Kim JE, Kim JH, Kim OL, Paek SH, Kim DG, Chi JG, Jung HW (2004) Surgical treatment of symptomatic Rathke cleft cysts: clinical features and results with special attention to recurrence. J Neurosurg 100(1):33–40 Aho CJ, Liu C, Zelman V, Couldwell WT, Weiss MH (2005) Surgical outcomes in 118 patients with Rathke cleft cysts. J Neurosurg 102(2):189–193 Eguchi K, Uozumi T, Arita K, Kurisu K, Yano T, Sumida M, Takechi A, Pant B (1994) Pituitary function in patients with Rathke's cleft cyst: significance of surgical management. 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NMC Case Rep J 12:79–84 Tables Table 1: Comparison of characteristics between headache and non-headache groups Headche (n=27) Non headache (n=24) Univariate analysis Multiple regression analysis with stepwise method Female (%) 21 (76%) 16 (65%) 0.374 - Age (year) 40.2(13-68) 48.3(14-73) 0.041 * - Visual disturbance (%) 2(7%) 15(63%) 0.002 ** 0.0026 ** Hyperprolactinemia (ng/ml) 16(2-42) 19(5-65) 0.329 - Hypopituitarism (%) 2(7%) 5(21%) 0.084 - Cyst size (mm) 10.1(6-22) 17.3(8-23) 0.0017 ** 0.0009 ** T1 hyper intense (%) 20 (74%) 11 (46%) 0.021 * - Intracystic nodule (%) 17 (62%) 6(25%) 0.013 * - Pearson’s correlation analysis or t-test were used as univariate analysis. Minus (-) indicates a factor which was not chosen as a possible explanatory variable. *p<0.05, **p<0.01 Table 2: Comparison of characteristics of improved and non-improved headache groups Improvement (n=14) Non-improvement (n=7) Univariate analysis Episodic headache 50% (7/14) 14% (1/7) 0.112 Headache location Frontal/behind the eyes:64% (9/14) others:37% (5/14) Frontal/behind the eyes: 14% (1/7) others:86% (6/7) 0.031 * Cyst size (mm) 10.1 10.2 0.366 T1 hyper intense 93% (13/14) 71%(5/7) 0.185 Intra cystic nodule 71%(10/14) 29%(2/7) 0.061 Analgesics and/or tranquilizers 14% (2/14) 85% (6/7) 0.001 ** Cyst reaccumulation 7%(1/14) 14%(1/7) 0.599 Pearson’s correlation analysis or t-test were used as univariate analysis. *p<0.05 **p<0.01 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 09 Feb, 2026 Read the published version in Neurosurgical Review → Version 1 posted Editorial decision: Revision requested 11 Dec, 2025 Reviews received at journal 04 Dec, 2025 Reviews received at journal 03 Dec, 2025 Reviewers agreed at journal 24 Nov, 2025 Reviewers agreed at journal 23 Nov, 2025 Reviewers agreed at journal 23 Oct, 2025 Reviews received at journal 13 Oct, 2025 Reviewers agreed at journal 13 Oct, 2025 Reviewers agreed at journal 11 Oct, 2025 Reviewers invited by journal 11 Oct, 2025 Editor assigned by journal 05 Oct, 2025 Submission checks completed at journal 02 Oct, 2025 First submitted to journal 30 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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13:57:12","extension":"xml","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":62376,"visible":true,"origin":"","legend":"","description":"","filename":"17a1da7e7e1842c599bcbcc16dc8a8c61structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7747251/v1/875e1f7cf0365c72a7d13195.xml"},{"id":94396740,"identity":"a179a26c-4c51-4f0f-98a9-43d780f629b1","added_by":"auto","created_at":"2025-10-27 13:56:13","extension":"html","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":73034,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7747251/v1/d8d9de8669d94ca68b9aa605.html"},{"id":94398065,"identity":"11de9046-d295-4c4f-a073-714a0f87aad5","added_by":"auto","created_at":"2025-10-27 13:56:57","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":167117,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart showing the inclusion and exclusion criterion of the patient cohort in the study.\u003c/p\u003e","description":"","filename":"Picture1.png","url":"https://assets-eu.researchsquare.com/files/rs-7747251/v1/f591f94039c827d2c4bd50e3.png"},{"id":94397798,"identity":"6a299fac-d55f-440b-ae76-de26d6a816d8","added_by":"auto","created_at":"2025-10-27 13:56:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":984512,"visible":true,"origin":"","legend":"\u003cp\u003eThe sagittal T1-weighted image showed a tumor within the sella turcica (A). Gadolinium-enhanced T1-weighted sagittal images demonstrated contrast enhancement of the pituitary gland surrounding the cyst (B). The coronal T2-weighted image showed intracystic nodule (arrow: hypo intense signal) within the cyst (C). The MRI following the first surgery showed resolution of the cyst (D). Five years after the first surgery, the MRI revealed a recurrence of the cyst (E). One year after the second surgery, MRI showed abdominal fat filling the cyst cavity without cyst recurrence (F).\u003c/p\u003e","description":"","filename":"Picture2.png","url":"https://assets-eu.researchsquare.com/files/rs-7747251/v1/0108f3b415c9deb594d25035.png"},{"id":102785466,"identity":"62aa5e95-4022-4ad0-af50-335b29c66f08","added_by":"auto","created_at":"2026-02-16 16:07:05","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2486127,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7747251/v1/a0a7746e-687a-4ad4-a9be-ae4489b9df0f.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical characteristics and long-term outcome in patients with Rathke’s cleft cysts associated with headache","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRathke\u0026rsquo;s cleft cysts (RCCs) are benign cystic lesions that occur in the sella turcica and suprasellar region. RCCs are generally asymptomatic and are detected incidentally on imaging studies associated with trauma or dizziness etc.\u003csup\u003e1)\u003c/sup\u003e However, RCCs are sometimes symptomatic, presenting with visual dysfunction, endocrine disturbances, and headaches.\u003csup\u003e2)\u003c/sup\u003e Visual symptoms associated with RCCs are caused by cystic compression of the optic chiasm. Surgical drainage of cyst contents relieves pressure on the optic chiasm and improves visual symptoms.\u003csup\u003e3)\u003c/sup\u003e With regard to endocrine disturbances in RCCs, it is reported that inflammation within the cysts as well as pressure of the cysts on the pituitary gland is involved. \u003csup\u003e6)\u003c/sup\u003e Postoperative improvement in endocrine function has been reported to be worse than improvement in visual dysfunction.\u003csup\u003e4), 5)\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eAlthough the mechanism of headache associated with RCCs is not clear, mass effect on dura, inflammation within the cyst, or secretion of the cyst contents into the subarachnoid space have been postulated.\u003csup\u003e7), 8)\u003c/sup\u003e Postoperative improvement rates for headache associated with RCCs vary from 40\u0026ndash;100%.\u003csup\u003e7), 9), 10), 11), 12), 13)\u003c/sup\u003e It is speculated that these difference rates may be due to the short follow-up period and the fact that the patients may have had other headaches such as migraine or tension headaches. This study conducted the long-term outcome of headache in patients with RCCs more than three years after transsphenoidal surgery. In addition to the outcome of headache, these patients are compared to RCC patients without headache to clarify their characteristics.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eSubjects\u003c/h2\u003e\u003cp\u003eThe institutional review board approved this retrospective study (No. 2023\u0026thinsp;\u0026minus;\u0026thinsp;361) and waived the requirement to obtain informed consent. We retrospectively studied the records of all patients who were treated at Kanazawa University Hospital for a RCCs as an initial treatment between January 2010 and March 2022. Fifty-five patients were selected. Of these patients, thirty-one patients had episodes of headache within 3 months of the surgery, but 4 had an obvious cause for their headache. Two patients had hyponatremia, one had acute sinusitis and one had head trauma. These 4 patients were excluded from this study as headaches not associated with RCCs. As a result, 27 patients were assigned to RCCs with headache (headache group). Meanwhile, the remaining 24 patients were assigned as RCC patients without headache (non-headache group).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eMR Images\u003c/h3\u003e\n\u003cp\u003ePreoperative MR images of the pituitary region were obtained for all selected patients, using a 3-Tesla magnet strength scanner (MAGNETOM Trio, Siemens, Germany or Signa Excite HDx 3.0T, GE Healthcare, Japan) with a 32-channel head coil. Pre-enhanced T1-, T2-weighted, and post-enhanced T1-weighted images were taken for all patients in the sagittal and coronal planes with 1.5 mm slice thickness. In order to identify pituitary gland and cyst wall, dynamic T1-weighted fast spin echo sequences were also acquired during the injection of 10 cc gadolinium followed by 20 cc of normal saline at a standard rate of 3 cc/s. The maximum cyst size (diameter) was measured in the coronal plane on a T1-weighted post-enhanced image. Radiologic evaluation of cyst contents was undertaken as follows: signal intensities of cyst contents in both T1- and T2- weighted images. A small lesion that were very hypo intense within the cyst at T2 image were evaluated as \u0026ldquo;intra cystic nodule\u0026rdquo;, which are characteristic of RCCs.\u003csup\u003e17)\u003c/sup\u003e Postoperative imaging evaluations were performed at 3 to 6 months. If there was no recurrence, a follow-up MRI was performed once a year. Cyst reaccumulation was defined as when the maximum diameter of the cyst on the last MRI was the same as the preoperative diameter.\u003c/p\u003e\n\u003ch3\u003eEndocrinological Evaluation\u003c/h3\u003e\n\u003cp\u003eEndocrinological status was examined both pre- and postoperatively and included determining levels of plasma growth hormone, prolactin, adrenocorticotropic hormone, cortisol, thyroid stimulating hormone, thyroid hormone (free T3 and T4), luteinizing hormone, and folliclestimulating hormone. Hyperprolactinemia was defined as elevated PRL above the normal range for sex. Urine volume and gravity were evaluated to diagnose diabetes insipidus.\u003c/p\u003e\n\u003ch3\u003eSurgical Procedures\u003c/h3\u003e\n\u003cp\u003eAll patients were treated with endoscopic transsphenoidal operations. Surgery for RCCs was indicated when headaches were not controlled with painkillers and disturbed patients\u0026rsquo; daily lives. Our surgical procedure for this series of RCCs is the standard one. After incision of the dura matter and cyst wall, the cyst content was drained out sufficiently and the cyst wall was resected partially for pathologic diagnosis. Sellar floor reconstruction was not performed unless cerebrospinal fluid (CSF) leakage was present. If a CSF leak was identified, repair was performed using an autologous subcutaneous fat graft from the abdomen to reconstruct the sellar dura.\u003c/p\u003e\n\u003ch3\u003ePostoperative Headache Survey\u003c/h3\u003e\n\u003cp\u003ePostoperative headache surveys were conducted at the time of annual follow-up MRI visits. As for patients who had lost their outpatient visits, we were interviewed by telephone. The outcome in headache was rated on a 5-point scale as follows; 1. Disappeared, 2. Improved, 3. Relapsed, 4. No change, 5. Worsened. In a subanalysis, patients with scale 1 and 2 were divided into the improvement group and patients with scale 3, 4, and 5 into the non-improvement group. Between these two groups, preoperative headache characteristics, cyst reaccumulation, use of analgesics and tranquilizers were examined. Flow chart of the participant inclusion process is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eFor statistical analysis, the patients were divided into headache and non-headache groups. Univariate analysis between the two groups was performed. The mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation and median are presented for parametric and nonparametric variables, respectively. The Mann\u0026ndash;Whitney U test was used to compare continuous data (e.g., cyst size), and the Fisher\u0026rsquo;s exact test was used to compare categorical data (e.g., sex) between the 2 groups. Multivariate stepwise logistic regression analysis was performed to detect independent predictors of the RCC patients with headache using factors that had significant associations in univariate analysis. All data were analysed using the JMP Pro statistical analysis software version 16.2.0 (SAS Institute Japan Inc., Tokyo, Japan) and\u003c/p\u003e\u003cp\u003eSPSS statistics 29.0.1.0. (IBM Japan Ltd., Tokyo, Japan). Statistical significance was set at a p-value of \u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003ePatient Characterization\u003c/h2\u003e\u003cp\u003eThe baseline characteristics of the patients with and without headache are shown in Table\u0026nbsp;1. Female accounted for 76% of the headache group and 65% of the non-headache group (P\u0026thinsp;=\u0026thinsp;0.374). The headache group was significantly younger than the non-headache group (40.2 vs 48.3 years, P\u0026thinsp;=\u0026thinsp;0.041). Significantly fewer patients in the headache group had visual dysfunction than in the non-headache group (7% vs 63%, P\u0026thinsp;=\u0026thinsp;0.002). With regard to endocrinological disturbances, there were no significant differences between the two groups in mean hyperprolactinemia (16 vs 19 ng/ml P\u0026thinsp;=\u0026thinsp;0.329) or in the percentage of hypopituitarism (7.4% vs 20.8%, P\u0026thinsp;=\u0026thinsp;0.084). Comparison on MRI showed significantly smaller cysts in the headache group (10.1 vs 17.3 mm, P\u0026thinsp;=\u0026thinsp;0.0017). In the evaluation of cyst content, high intense on T1-weighted images was significantly higher in the headache group than in the non-headache group (74% vs 46%, P\u0026thinsp;=\u0026thinsp;0.021). Comparison of intracystic nodules on T2-weighted images also showed a significantly higher in the headache group (62% vs 25%, P\u0026thinsp;=\u0026thinsp;0.013).\u003c/p\u003e\u003cp\u003eSubsequently, the multiple regression analysis was performed. To identify the independent variables related to the headache, a stepwise analysis was carried out using the following items: female, age, visual disturbance, cyst size, T1 hyper intense and intracystic nodule. Visual disturbance and cyst size were the factors associated with the headache. These variables were used as the independent variable in the regression analysis. Visual disturbance (p\u0026thinsp;=\u0026thinsp;0.0026) and cyst size (p\u0026thinsp;=\u0026thinsp;0.0009) were significantly correlated with the headache.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003ePostoperative Headache Survey\u003c/h2\u003e\u003cp\u003eOf the 27 patients in the headache group, 21 were able to be assessed for headache after surgery. The remaining six could not be interviewed because they could not be contacted. Sixteen of the 21 were interviewed during the annual follow-up MR image at clinic. The remaining 5 patients were interviewed by telephone because they had moved or other reasons. At the time of the survey, the mean time since surgery was 5.3 (\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8 CR9 CR10 CR11\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) years. The outcome for headache was classified into five categories, with the following results. 1. Disappeared: after surgery, headache completely disappeared in 5/21 patients (23%). 2. Improvement: although headaches improved compared to preoperatively, 9/21 (43%) of the patients reported that they still had headaches. 3. Relapsed: five (24%) patients experienced headache resolution immediately after surgery, but it recurred and remained as severe as before surgery. 4. No change: two patients (10%) had no improvement in headache after surgery. 5. Worsened: no patient's headache was worse than preoperatively. As a subanalysis, categories 1 and 2 were defined as headache improvement group, and the 3, 4, and 5 were defined as non-improvement group. Clinical characteristics were compared between the improved and non-improved groups (Table\u0026nbsp;2). Half of the patients in the improved headache group complained of episodic headache (occurring in sudden, intermittent episodes) before surgery, although not significantly different than those in the non-improvement group (50% vs 14%, P\u0026thinsp;=\u0026thinsp;0.112). Regarding the location of the headache, the frontal region and/or behind the eyes was significantly more common in the headache group (64% vs 14%, P\u0026thinsp;=\u0026thinsp;0.031). Other sites in the improved group included the temporal region in 21%, the whole head in 15%. Cyst size on preoperative MRI was similar in the improved and non-improved groups (10.1 vs 10.2 mm, P\u0026thinsp;=\u0026thinsp;0.366). Regarding cyst contents, T1 high intense findings were comparable in both groups (93% vs 71%, P\u0026thinsp;=\u0026thinsp;0.185). In intracystic nodules, there was no significant difference, although there were more frequently in the improved group (71% vs 29%, P\u0026thinsp;=\u0026thinsp;0.061). Significantly fewer patients in the improvement group were taking analgesics and/or tranquilizers at the time of the survey (14% vs 85%, P\u0026thinsp;=\u0026thinsp;0.001). Postoperatively, there was one case each in the improvement and non-improvement groups that presented cyst reaccumulation on MRI (7% vs 14%, P\u0026thinsp;=\u0026thinsp;0.599). The one of the patients underwent reoperation due to relapse headache and reaccumuration of the cyst. The headache disappeared again, after the second surgery (Illustrative case).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eIllustrative Case\u003c/h2\u003e\u003cp\u003eA 29-year-old woman experienced a sudden headache behind her eyes. The pain persisted the next day, so she visited the outpatient clinic. A head CT scan revealed a high-density mass in the sella turcica. MRI showed a cyst with high signal intense on T1 weighted image and high signal intense with intracystic nodule on T2 weighted image, with no contrast enhancement within the cyst (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA-C). She was referred to our hospital, and we diagnosed the mass as a RCC. She had been taking painkillers for about one month, but they were ineffective. She returned to our hospital and surgery was planned. Baseline serum pituitary hormone levels, excluding prolactin (28 ng/ml), were within the normal range. Endoscopic transnasal transsphenoid surgery was performed. Clear and viscous cystic fluid was drained. The specimen contained ciliated epithelial cells, confirming the diagnosis of RCC. The headaches completely resolved postoperatively. Follow-up MRI were performed four times over a three-year period, and no cyst recurrence was observed (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD). Five years after the surgery, she experienced a recurrence of headaches and visited our hospital. The cyst had refilled to the same size as before the surgery (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eE). A second surgery was performed, and the cyst contents were drained again. To prevent cerebrospinal fluid leakage, abdominal fat was grafted into the sella turcica during surgery. The headache has completely resolved, and one year have passed since the second surgery. There has been no recurrence of headache, reaccumulation of the cyst (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eF) and pituitary dysfunction.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study analysed the clinical characteristics, imaging features, and long-term outcomes in patients with RCCs, focusing particularly on those with associated headaches. Several key findings emerge from this investigation, offering insights into the relationship between RCCs and headache symptoms, as well as the efficacy of surgical intervention.\u003c/p\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003ePathophysiology of Headaches in RCCs and Imaging Features\u003c/h2\u003e\u003cp\u003ePatients with RCC-associated headaches were found to have distinct clinical and radiological features compared to those without headaches in this study. Headaches were more prevalent in younger patients and those with smaller cyst sizes, suggesting that factors other than cyst compression, such as inflammation or secretion of cyst contents, may play a critical role in symptom generation. The presence of T1 hyper intense signal and intracystic nodules on MRI were significantly associated with the headache group in univariate analysis, consistent with previous studies indicating that these features might reflect inflammatory processes or biochemical irritants contributing to headache pathophysiology.\u003csup\u003e7), 8), 17)\u003c/sup\u003e Interestingly, multivariate analysis also showed that no visual impairment or small cysts were associated with headaches. These results may be important in considering the mechanism of headache in RCCs. One possibility is that cyst fluid periodically leaks into the subarachnoid space, causing headaches and keeping the cyst small. Therefore, headaches occur without the cyst compressing the optic chiasm. Previous reports have also noted spontaneous regression of RCC in patients with severe headache, suggesting rupture of the cyst into the subarachnoid space.\u003csup\u003e20), 21), 22)\u003c/sup\u003e Such imaging biomarkers could be helpful in identifying patients at higher risk for headaches and tailoring their treatment strategies. Further investigations using advanced imaging and biochemical analyses of cystic contents may help elucidate these mechanisms.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003ePostoperative Outcomes\u003c/h2\u003e\u003cp\u003eSurgical intervention via transsphenoidal surgery demonstrated variable success in resolving headaches. The improvement rate of postoperative headache in RCCs in previous publications is quite high, ranging from 75\u0026ndash;94%. \u003csup\u003e7), 10), 12), 15) 17) 18)\u003c/sup\u003e In our study, 66% of patients experienced either complete resolution or improvement in symptoms. We speculate that the reason for the lower rate of headache improvement compared to previous papers is the difference in the timing of headache evaluation. In most of the previous papers, the timing of headache evaluation was undocumented, probably because the evaluation was performed immediately after surgery or several months after surgery. On the other hand, our paper analyzes the long-term outcome of headaches, with the average time of headache assessment being approximately 5 years post-surgery. In any case, these improvement rates highlight the potential efficacy of surgical drainage in alleviating headache-related discomfort. However, the persistence or recurrence of headaches in a subset of patients underscores the multifactorial nature of these symptoms, which may also be influenced by pre-existing headache disorders, such as migraines or tension-type headaches.\u003csup\u003e8), 9)\u003c/sup\u003e Improved headache outcomes were associated with fewer postoperative requirements for analgesics or tranquilizers, indicating that surgical intervention might also reduce the reliance on symptomatic medication. These findings support the consideration of surgery as a viable option for symptom relief in appropriately selected patients. As for predictors of surgical success, preoperative headache characteristics, such as episodic patterns and specific locations (e.g., frontal or retro-orbital areas), appeared to influence outcomes. Patients with episodic headaches had better postoperative outcomes, suggesting that headache subtype and localization may guide surgical decision-making. \u003csup\u003e7),8)\u003c/sup\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eLimitations and Future Directions\u003c/h2\u003e\u003cp\u003eThis study is limited by its retrospective design, single-center setting, and reliance on subjective headache assessments. Future prospective studies with larger sample sizes and objective headache scoring systems are needed to validate these findings. In addition, since data on preoperative headache history (migraine, etc.) is not available, there is a possibility of confusion with primary headache. Additionally, incorporating biochemical analyses of cyst contents and advanced imaging modalities could provide deeper insights into the mechanisms underlying RCC-associated headaches. Exploring adjunctive therapies such as targeted anti-inflammatory treatment may also contribute to improving headaches in RCC.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study highlights the clinical significance of headaches in RCC patients and identifies key imaging and clinical predictors of their occurrence. While transsphenoidal surgery is effective for many, its success in resolving headaches varies, reflecting the complexity of their pathophysiology. Further research is necessary to improve the diagnostic and therapeutic approaches for RCC-associated headaches, ultimately enhancing patient care and quality of life.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e:\u003c/h2\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Kanazawa University Hospital (Approval No. 2023\u0026thinsp;\u0026minus;\u0026thinsp;361). All the procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional or national research committee and with either the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. For this type of study, formal consent was not required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors agreed for the publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors agreed to participate in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\n\u003cp\u003e\u0026quot;Y.S. wrote the main manuscript text. T.I. prepared figures. R.K., S.T. and M. O. collected the clinical data. R.N. performed statistical processing. M.N. revised the manuscript. All authors reviewed the manuscript.\u0026quot;\u003c/p\u003e\n\u003ch2\u003eAcknowledgments:\u003c/h2\u003e\n\u003cp\u003eNo specific funding was provided for this work.\u003c/p\u003e\n\u003ch2\u003eData Availability\u003c/h2\u003e\n\u003cp\u003eData and pictures shown in the manuscript will be available on demand.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCulver SA, Grober Y, Ornan DA, Patrie JT, Oldfield EH, Jane JA Jr, Thorner MO (2015) A Case for Conservative Management: Characterizing the Natural History of Radiographically Diagnosed Rathke Cleft Cysts. J Clin Endocrinol Metab 100(10):3943\u0026ndash;3948\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKim JE, Kim JH, Kim OL, Paek SH, Kim DG, Chi JG, Jung HW (2004) Surgical treatment of symptomatic Rathke cleft cysts: clinical features and results with special attention to recurrence. J Neurosurg 100(1):33\u0026ndash;40\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAho CJ, Liu C, Zelman V, Couldwell WT, Weiss MH (2005) Surgical outcomes in 118 patients with Rathke cleft cysts. J Neurosurg 102(2):189\u0026ndash;193\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEguchi K, Uozumi T, Arita K, Kurisu K, Yano T, Sumida M, Takechi A, Pant B (1994) Pituitary function in patients with Rathke's cleft cyst: significance of surgical management. Endocr J 41(5):535\u0026ndash;540\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAlsavaf MB, Wu KC, Gosal JS, Finger G, Koch B, Abouammo MD, Prevedello LM, Carrau RL, Prevedello DM (2023) Endoscopic endonasal marsupialization of rathke cleft cysts: clinical outcomes and risk factors analysis of visual impairment, pituitary dysfunction, and CSF leak. Pituitary 26(6):696\u0026ndash;707\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOishi M, Hayashi Y, Sasagawa Y, Kita D, Tachibana O, Nakada M (2018) Outcome of diabetes insipidus in patients with Rathke's cleft cysts. Clin Neurol Neurosurg 167:141\u0026ndash;146\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNishioka H, Haraoka J, Izawa H, Ikeda Y (2006 Nov-Dec) Headaches associated with Rathke's cleft cyst. Headache 46(10):1580\u0026ndash;1586\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCote DJ, Besasie BD, Hulou MM, Yan SC, Smith TR, Laws ER (2016) Transsphenoidal surgery for Rathke\u0026rsquo;s cleft cyst can reduce headache severity and frequency. Pituitary 19(1):57\u0026ndash;64\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJahangiri A, Potts M, Kunwar S, Blevins L, El-Sayed IH, Aghi MK (2014) Extended endoscopic endonasal approach for suprasellar Rathke's cleft cysts. J Clin Neurosci 21(5):779\u0026ndash;785\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePotts MB, Jahangiri A, Lamborn KR, Blevins LS, Kunwar S, Aghi MK (2011) Suprasellar Rathke cleft cysts: clinical presentation and treatment outcomes. Neurosurgery 69(5):1058\u0026ndash;1068 discussion 1068-7\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMidha R, Jay V, Smyth HS (1991) Transsphenoidal management of Rathke's cleft cysts. A clinicopathological review of 10 cases. Surg Neurol 35(6):446\u0026ndash;454\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePark JK, Lee EJ, Kim SH (2012) Optimal surgical approaches for Rathke cleft cyst with consideration of endocrine function. Neurosurgery 70(2 Suppl Operative):250\u0026ndash;256 discussion 256-7\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoutourousiou M, Grotenhuis A, Kontogeorgos G, Seretis A (2009) Treatment of Rathke's cleft cysts: experience at a single centre. J Clin Neurosci 16(7):900\u0026ndash;903\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang X, Wang D, Wang H, Cai Y, Jiang X, Heng L, Qu Y (2024) Endoscopic endonasal resection of symptomatic Rathke's cleft cysts: outcomes of the strategy to maintain the fenestration open. Neurosurg Rev 47(1):253\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCabuk B, Selek A, Emengen A, Anik I, Canturk Z, Ceylan S (2019) Clinicopathologic Characteristics and Endoscopic Surgical Outcomes of Symptomatic Rathke's Cleft CystsWorld Neurosurg. Dec 132:e208\u0026ndash;e216\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLin M, Wedemeyer MA, Bradley D, Donoho DA, Fredrickson VL, Weiss MH, Carmichael JD, Zada G (2019) Long-term surgical outcomes following transsphenoidal surgery in patients with Rathke\u0026rsquo;s cleft cysts J. Neurosurg 130(3):831\u0026ndash;837\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBinning MJ, Gottfried ON, Osborn AG, Couldwell WT (2005) Rathke cleft cyst intracystic nodule: a characteristic magnetic resonance imaging finding. J Neurosurg 103(5):837\u0026ndash;840\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBenveniste RJ, King WA, Walsh J, Lee JS, Naidich TP, Post KD (2004) Surgery for Rathke cleft cysts: technical considerations and outcomes. J Neurosurg 101(4):577\u0026ndash;584\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee JS, Kim YH, Koh EJ, Phi JH, Lee JY, Kim KH, Wang KC, Cheon JE, Park SH, Lee YA, Shin CH, Kim SK (2023) Surgical indication of pediatric Rathke's cleft cyst based on a 20-year retrospective cohort. J Neurosurg Pediatr 32(6):729\u0026ndash;738\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTruong LUF, Marlier B, Decoudier B, Litr\u0026eacute; CF, Barraud S (2022) Vanishing Rathke's cleft cyst. Ann Endocrinol (Paris) 83(4):260\u0026ndash;262\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNishio S, Morioka T, Suzuki S (2001) Spontaneous regression of a pituitary cyst: report of two cases. Clin Imaging 25(1):15\u0026ndash;17\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKondo Y, Sasagawa Y, Tamai S, Nakada M (2025) Spontaneous Regression of Rathke's Cleft Cysts: A Report of Three Cases. NMC Case Rep J 12:79\u0026ndash;84\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"645\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 645px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1: Comparison of characteristics between headache and non-headache groups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 185px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 15.7117%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHeadche (n=27)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2661%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon headache \u0026nbsp; (n=24)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultiple regression analysis\u0026nbsp;\u003cbr\u003e\u0026nbsp;with stepwise method\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 185px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFemale (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.7117%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e21 (76%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2661%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e16 (65%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.374\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 185px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge (year)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.7117%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e40.2(13-68)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2661%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e48.3(14-73)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.041\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 185px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVisual disturbance (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.7117%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2(7%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2661%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e15(63%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.002\u003csup\u003e**\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0026\u003csup\u003e**\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 185px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHyperprolactinemia (ng/ml)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.7117%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e16(2-42)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2661%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e19(5-65)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.329\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 185px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHypopituitarism (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.7117%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e2(7%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2661%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e5(21%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.084\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 185px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCyst size (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.7117%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e10.1(6-22)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2661%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e17.3(8-23)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0017\u003csup\u003e**\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.0009\u003csup\u003e**\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 185px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT1 hyper intense (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.7117%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e20 (74%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2661%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e11 (46%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.021\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 185px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntracystic nodule (%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15.7117%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e17 (62%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 16.2661%;\"\u003e\n \u003cp\u003e\u003cstrong\u003e6(25%)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.013\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e-\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 645px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePearson\u0026rsquo;s correlation analysis or t-test were used as univariate analysis. Minus (-) indicates a factor which was not chosen as a possible explanatory variable. *p\u0026lt;0.05, **p\u0026lt;0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"647\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 647px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTable 2: Comparison of characteristics of improved and non-improved headache groups\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 173px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eImprovement (n=14)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNon-improvement (n=7)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate analysis\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEpisodic headache\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e50% (7/14)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e14% (1/7)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.112\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHeadache location\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrontal/behind the eyes:64% (9/14) \u0026nbsp; \u0026nbsp; others:37% (5/14)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFrontal/behind the eyes: 14% (1/7) others:86% (6/7)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.031\u003csup\u003e*\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCyst size (mm)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e10.1\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e10.2\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.366\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eT1 hyper intense\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e93% (13/14)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e71%(5/7)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.185\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntra cystic nodule\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e71%(10/14)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e29%(2/7)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.061\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAnalgesics and/or tranquilizers\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e14% (2/14)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e85% (6/7)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.001\u003csup\u003e**\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 173px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCyst reaccumulation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 160px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e7%(1/14)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 172px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e14%(1/7)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 141px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.599\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 647px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePearson\u0026rsquo;s correlation analysis or t-test were used as univariate analysis. *p\u0026lt;0.05 **p\u0026lt;0.01\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"neurosurgical-review","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nrev","sideBox":"Learn more about [Neurosurgical Review](https://www.springer.com/journal/10143)","snPcode":"10143","submissionUrl":"https://submission.nature.com/new-submission/10143/3","title":"Neurosurgical Review","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Rathke’s cleft cyst, headache, transsphenoidal surgery, MRI","lastPublishedDoi":"10.21203/rs.3.rs-7747251/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7747251/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThis study aimed to investigate the clinical features and long-term outcomes of patients with Rathke\u0026rsquo;s cleft cysts (RCCs) presenting with headaches.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA retrospective analysis was conducted on 51 patients who underwent transsphenoidal surgery for RCCs between 2009 and 2022. Patients were divided into headache (n\u0026thinsp;=\u0026thinsp;27) and non-headache (n\u0026thinsp;=\u0026thinsp;24) groups. Clinical data, MRI findings, and surgical outcomes were analyzed. Headache improvement was assessed using a 5-point postoperative scale.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003ePatients in the headache group were significantly younger (40 vs 48\u0026nbsp;year: p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), had less visual disturbance (7% vs 63%: p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and had smaller cysts (10 mm vs 17 mm: p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). MRI showed a higher prevalence of T1 hyper intense (74% vs 46%: p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) and intracystic nodules (62% vs 25%: p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in the headache group. Multivariate analysis identified less visual disturbance (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) and smaller cyst (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01) as independent predictors of headache presence. Postoperative follow-up (mean: 5.3 years) revealed that 66% of patients experienced headache resolution or improvement, while 34% reported persistent or recurrent symptoms. Resolution or improvement after surgery correlated with less frequent use of analgesics and specific headache characteristics (frontal/retro-orbital location).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIn patients with RCCs, larger cyst size does not necessarily correlate with the presence of headache, indicating that factors such as inflammation may contribute to symptom development. Surgical intervention offers sustained relief in many cases, though long-term outcomes vary. Further research is needed to clarify mechanisms and optimize treatment strategies.\u003c/p\u003e","manuscriptTitle":"Clinical characteristics and long-term outcome in patients with Rathke’s cleft cysts associated with headache","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-26 00:51:03","doi":"10.21203/rs.3.rs-7747251/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-11T11:48:31+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-04T11:28:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-03T10:35:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"52908394545763087775849312985993975988","date":"2025-11-24T07:50:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"208675539340424598569637504982464461244","date":"2025-11-23T17:11:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"13206432380160589169926122415599161326","date":"2025-10-23T14:57:47+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-13T18:35:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"318007435630904442548608233108383930171","date":"2025-10-13T18:29:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"191528773525080786945838406087039848065","date":"2025-10-11T21:20:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-10-11T16:53:29+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-10-05T20:50:11+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-03T03:47:46+00:00","index":"","fulltext":""},{"type":"submitted","content":"Neurosurgical Review","date":"2025-09-30T04:57:50+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"neurosurgical-review","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"nrev","sideBox":"Learn more about [Neurosurgical Review](https://www.springer.com/journal/10143)","snPcode":"10143","submissionUrl":"https://submission.nature.com/new-submission/10143/3","title":"Neurosurgical Review","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"16b397c8-3b8f-44d6-ad59-d9d322fd964d","owner":[],"postedDate":"October 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-16T16:04:50+00:00","versionOfRecord":{"articleIdentity":"rs-7747251","link":"https://doi.org/10.1007/s10143-026-04141-z","journal":{"identity":"neurosurgical-review","isVorOnly":false,"title":"Neurosurgical Review"},"publishedOn":"2026-02-09 15:57:17","publishedOnDateReadable":"February 9th, 2026"},"versionCreatedAt":"2025-10-26 00:51:03","video":"","vorDoi":"10.1007/s10143-026-04141-z","vorDoiUrl":"https://doi.org/10.1007/s10143-026-04141-z","workflowStages":[]},"version":"v1","identity":"rs-7747251","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7747251","identity":"rs-7747251","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}