Rathke's cleft cysts: from pathophysiology to management.

Rathke's cleft cysts (RCCs) are benign, non-neoplastic lesions located in the sellar and suprasellar regions of the brain, originating from remnants of Rathke's pouch, an embryonic precursor to the anterior pituitary gland. Although RCCs are frequently asymptomatic and discovered incidentally during imaging studies, they can present with a variety of symptoms, including headaches, visual disturbances, and endocrine dysfunction due to the compression of adjacent neural structures. The management of RCCs is particularly challenging, as the decision to pursue conservative monitoring or surgical intervention depends heavily on the cyst's size, growth potential, and the severity of symptoms. Transsphenoidal surgery is the primary treatment for symptomatic RCCs, offering effective relief from symptoms through decompression of the cyst. However, recurrence remains a significant issue, with rates reported up to 33%, prompting debates about the extent of cyst wall removal during surgery. Recent advancements in minimally invasive endoscopic techniques have improved surgical outcomes, yet the risk of postoperative complications such as hypopituitarism and cerebrospinal fluid leaks persists. Additionally, stereotactic radiosurgery has emerged as a potential alternative for patients with recurrent RCCs or those who are not suitable candidates for repeat surgery. Despite its promise, the long-term safety and efficacy of radiotherapy in RCC management require further investigation. This narrative review aims to provide a comprehensive overview of RCCs, integrating the latest research and clinical guidelines to discuss pathophysiology, clinical presentation, and management strategies, emphasizing the need for a personalized approach to treating this complex condition.

Case report: Spontaneous improvement and treatment considerations in leukoencephalopathy with calcifications and cysts.

We present the case of a patient with leukoencephalopathy with calcifications and cysts (LCC), who experienced progressive severe hemiparesis despite multiple neurosurgical interventions of a large contralateral cyst. Bevacizumab was proposed as an ultimate treatment option based on prior case reports. While awaiting reimbursement approval for bevacizumab, major improvement occurred in both clinical and radiological disease manifestations. The disease course of LCC is variable and unpredictable; neurosurgical treatment should be reserved for severe and progressive neurological deficits. Bevacizumab has been reported as a promising alternative treatment option. Importantly, in our case the observed clinical improvement would have been attributed to the effects of bevacizumab, if started when requested. Our case underscores the need for a natural history study for LCC and the necessity of validating treatment efficacy by systematic evaluation through appropriate clinical trials rather than relying on anecdotal evidence from published case reports.

Endonasal endoscopic or endoscopic-assisted transcranial surgery of Rathke's cleft cysts: does the approach and surgical technique influence the radicality and recurrence rate?

OBJECTIVE: Resections of symptomatic Rathke's cleft cysts (RCCs) are mainly performed via an endonasal transsphenoidal approach. However, there is a lack of equivalent data in current literature concerning transcranial keyhole approach in the treatment of RCCs. In order to find general recommendations for the surgical treatment of RCCs also with regard to recurrence, the object of this study is the analysis and comparison of both techniques. METHODS: Twenty-nine patients having been surgically treated between January 2004 and August 2019 were retrospectively analysed. The transsphenoidal approach was chosen in 16 cases and the transcranial keyhole approach in 13 cases. Both surgical techniques were analyzed and compared concerning preoperative symptoms and cyst characteristics, complications, surgical radicality, endocrinological and ophthalmological outcome and recurrences in patients´ follow up. RESULTS: The postoperative outcome of both techniques was identic and showed highly satisfying success rates with 92% for neurological deficits, 82% for endocrinological dysfunctions and 86% for visual deficits. In contrast, momentous postoperative complications were significantly more likely after transsphenoidal operations. After a mean follow-up time of 5.7 years, the recurrence rates of both cohorts were the same with 0% each. CONCLUSIONS: Regarding its equal outcome with its lower complication rate, the authors suggest using the supraorbital keyhole approach for RCCs whose anatomical configuration allow both techniques. Yet, the decision should always consider the surgeon's personal experience and other individual patient characteristics. Further studies with higher numbers of cases and longer follow-up periods are necessary to analyse the effect of the selected approach on recurrence.

The role of MRI biomarkers in evaluation of symptomatic pineal cysts - a retrospective analysis.

BACKGROUND: Our aim was to determine whether the Apparent Diffusion Coefficient is able to predict the presence of a symptomatic pineal cyst by detecting cerebral edema. METHODS: We retrospectively analyzed MRIs of 45 patients with pineal cysts before and after resection and 51 patients without pineal cysts, comparing ADC values of thalamus, central, periventricular and subcortical white matter. Furthermore we evaluated cyst size and morphology and analyzed its correlation to ADC values in corresponding patients. RESULTS: Differences between patients with symptomatic pineal cyst and control group were not significant (p = 0.200 - 0.968). ADC ratios did not change significantly after resection of the cyst (p = 0.575 - 0.862). Cyst size showed no significant correlation to ADC ratios (p = 0.071 - 0.918). Raw data analyses revealed more significance, especially periventricularly and in central white matter, which resulted in significant interhemispheric differences in ADC ratios in both subgroups (p < 0.001 and p = 0.031). MRI of 1.5T showed consistently higher values than 3T but mostly insignificant. CONCLUSION: Our analysis revealed no evidence that pineal cysts lead to intracerebral edema caused by venous compression. Since variability was higher than the differences seen, ADC sequences do not appear to be an appropriate diagnostic tool for symptomatic pineal cysts.

"Evaluating surgical approaches for Rathke's cleft cysts and sellar meningiomas: factors influencing treatment of choice".

This study reviews recent progress in the surgical treatment of Rathke's cleft cysts (RCCs) and Sellar region meningiomas, based on findings from three key studies. RCCs are benign, fluid-filled remnants from pituitary gland development that are usually asymptomatic and found by chance. However, surgical intervention is needed when they become symptomatic or increase in size. Research by Stefan Linsler et al. and others examines various surgical methods, including transcranial keyhole and transsphenoidal techniques for RCCs, and endoscopic endonasal and supraorbital keyhole approaches for Sellar meningiomas. The results show that both transcranial keyhole and transsphenoidal surgeries for RCCs have high success rates with no recurrences over 5.7 years, although the keyhole approach has fewer complications. For Sellar meningiomas, the choice between endoscopic endonasal and supraorbital keyhole techniques should be based on tumor characteristics, highlighting the importance of surgeon proficiency in both methods. These studies emphasize the need for personalized treatment strategies tailored to patient and tumor characteristics and highlight the importance of ongoing surgical skill development and further research to refine minimally invasive techniques. This study highlights the crucial role of personalized surgical approaches in improving outcomes for patients with RCCs and Sellar region meningiomas.

Natural history and surgical outcomes of Rathke's cleft cysts: a Spanish multicenter study.

Rathke's cleft cysts (RCC) are a common type of lesion found in the sellar or suprasellar area. They are usually monitored clinically, but in some cases, surgery may be required. However, their natural progression is not yet well understood, and the outcomes of surgery are uncertain. The objective of this study is to evaluate the natural history of Rathke's cleft cysts in patients who are clinically monitored without treatment, and to determine the outcomes of surgery and the incidence of recurrences over time. Design and patients: National multicentric study of patients diagnosed of Rathke's cleft cyst (RCC- Spain) from 2000 onwards and followed in 15 tertiary centers of Spain. A total of 177 patients diagnosed of RCC followed for 67.3 months (6-215) and 88 patients who underwent surgery, (81 patients underwent immediate surgery after diagnosis and 7 later for subsequent growth) followed for 68.8 months (3-235). Results: The cyst size remained stable or decreased in 73.5% (133) of the patients. Only 44 patients (24.3%) experienced a cyst increase and 9 of them (5.1%) experienced an increase greater than 3 mm. In most of the patients who underwent surgery headaches and visual alterations improved, recurrence was observed in 8 (9.1%) after a median time of 96 months, and no predictors of recurrence were discovered. Conclusions: Rathke's cleft cysts without initial compressive symptoms have a low probability of growth, so conservative management is recommended. Patients who undergo transsphenoidal surgery experience rapid clinical improvement, and recurrences are infrequent. However, they can occur after a long period of time, although no predictors of recurrence have been identified.

Endoscopic endonasal resection of symptomatic Rathke's cleft cysts: outcomes of the strategy to maintain the fenestration open.

PURPOSE: The study intends to clarify the optimal endoscopic endonasal surgical strategy for symptomatic Rathke's cleft cysts (RCCs). METHODS: We retrospectively analyzed patients with RCCs that underwent EEA surgery. The strategy for surgical and reconstruction method selection was presented. Patients were split into groups of fenestration open or closed. Pre- and postoperative symptoms, imaging, ophthalmologic, and endocrinologic exams were reviewed. The incidence of complications and the recurrence rates were determined. RESULTS: The 75 individuals were all received primary operations. The fenestration closed group contained 32 cases, while the fenestration open group contained 43 cases. The median follow-up period was 39 months. The three primary complaints were headache (n = 51, 68.00%), vision impairment (n = 45, 60.00%), and pituitary dysfunction (n = 16, 21.33%). Of the 51 patients with preoperative headaches, 48 (94.12%) reported improvement in their symptoms following surgery. Twenty-three out of 45 patients (51.11%) experienced an improvement in visual impairment. Pituitary dysfunction was found improved in 14 out of 16 individuals (87.50%). There was no discernible difference in the rate of symptom alleviation between both groups. There were three patients (3/75, 4.00%) had cyst reaccumulation. One of them (1/75, 1.33%), which needed reoperation, was healed using pterional approach. In term of complications, cerebral infections occurred in two patients (2/75, 2.67%). Both of them recovered after antibiotic treatment. No postoperative cerebrospinal fluid rhinorrhea occurred. One patient (1/75, 1.33%) in the open group experienced epistaxis. There was no persistent hypopituitarism or diabetes insipidus (DI). Analysis of headache related factors showed that the presence of wax like nodules was related to it. CONCLUSION: RCC was successfully treated with endoscopic endonasal surgery with few problems when the fenestration was kept as open as feasible. Preoperative identification of T2WI hypointense nodules may be a potential reference factor for surgical indication.

Lack of inflammation or immune response in cyst tissue of patients with symptomatic non-hydrocephalic pineal cysts.

Pineal cysts are frequently encountered as incidental findings in magnetic resonance imaging, usually devoid of symptoms, yet some patients exhibit symptomatic manifestations possibly associated with the cyst, even in the absence of hydrocephalus. The etiology of these symptoms remains contentious. This study aims to investigate the presence of lymphatic endothelial cell (LEC) markers and indications of inflammation or immune response within the pineal cysts of patients experiencing symptomatic non-hydrocephalic presentations. Eight patients who underwent surgical excision of their cysts were included in the study. Immunohistochemistry was utilized to assess the expression of LYVE-1, PDPN, and VEGFR3 as LEC markers, alongside IL-6 and CD3 for indications of inflammation or immune activity. Our analysis revealed an absence of inflammatory markers or immune response. However, a distinct expression of VEGFR3 was observed, likely localized to neurons within the pineal cyst tissue. We propose that these VEGFR3+ neurons within the pineal cyst may contribute to the headache symptoms reported by these patients. Further investigations are warranted to substantiate this hypothesis.

Features of Remyelination after Transplantation of Olfactory Ensheathing Cells with Neurotrophic Factors into Spinal Cord Cysts.

This paper shows for the first time that co-transplantation of human olfactory ensheathing cells with neurotrophin-3 into spinal cord cysts is more effective for activation of remyelination than transplantation of cells with brain-derived neurotrophic factor and a combination of these two factors. The studied neurotrophic factors do not affect proliferation and migration of ensheathing cells in vitro. It can be concluded that the maximum improvement of motor function in rats receiving ensheathing cells with neurotrophin-3 is largely determined by activation of remyelination.

Rathke's Cleft Cyst and Craniopharyngioma: A Continuum of the Same Spectrum? Insights from an Interesting Case and Previous Literature.

Rathke's Cleft Cysts (RCCs) and Craniopharyngiomas (CPs) may represent disease entities on the same etio-pathological spectrum. We report the case of a 36-year-old female presenting with vision loss and menstrual irregularities, imaging shows a predominantly cystic lesion in the sellar region with suprasellar extension. She underwent a microscopic transnasal resection of the lesion. She later presented with recurrent symptoms and increased residual lesion size on imaging, a transcranial excision of the lesion was performed. Histopathology from the initial operative specimen revealed RCC with squamous metaplasia which was BRAF negative, while the specimen from the second surgery revealed BRAF positive papillary stratified squamous architecture suggestive of Papillary CP. This case adds to the evidence that both RCCs and papillary CPs may be the spectrum of the same disease. Further, papillary CPs may be an evolution from the RCCs.

Appearance of fluid content in Rathke's cleft cyst is associated with clinical features and postoperative recurrence rates.

PURPOSE: The contents of Rathke's cleft cysts (RCCs) vary from clear and slightly viscous to purulent. Surgical treatment of symptomatic RCCs involves removing the cyst contents, whereas additional cyst-wall opening to prevent reaccumulation is at the surgeon's discretion. The macroscopic findings of the cyst content can reflect the nature of RCCs and would aid in surgical method selection. METHODS: We retrospectively reviewed the records of 42 patients with symptomatic RCCs who underwent transsphenoidal surgery at our institute between January 2010 and March 2022. According to the intraoperative findings, cyst contents were classified into type A (purulent), type B (turbid white with mixed semisolids), or type C (clear and slightly viscous). Clinical and imaging findings and early recurrence rate (within two years) were compared according to the cyst content type. RESULTS: There were 42 patients classified into three types. Patients with type C were the oldest (65.4 ± 10.4 years), and type A included more females (92.9%). For magnetic resonance imaging, type-A patients showed contrast-enhanced cyst wall (92.9%), type-B patients had intracystic nodules (57.1%), and all type-C patients showed low T1 and high T2 intensities with larger cyst volumes. Fewer asymptomatic patients had type C. Preoperative pituitary dysfunction was most common in type A (71.4%). Early recurrence was observed in types A and C, which were considered candidates for cyst-wall opening. CONCLUSION: The clinical characteristics and surgical prognosis of RCCs depend on the nature of their contents.

Imaging Feature of Leukoencephalopathy with Calcifications and Cysts (Labrune Syndrome).

Labrune syndrome is an uncommon central nervous system disorder characterized by leukoencephalopathy, cerebral calcifications, and cysts on brain imaging. The basic pathology is microangiopathy resulting from a mutation in the SNORD118 gene. Radiological imaging is the hallmark of the disease.

Management of Pediatric Cavum Cysts: A Scoping Review and a Single Institution Case Series.

INTRODUCTION: Pediatric cavum cysts are a rare yet complicated pathology to manage. The literature is scarce, primarily consisting of case series, and lacking a consensus regarding clear management. In this scoping review, we aimed to compile existing information in the literature regarding the management of pediatric cavum cysts across the last 10 years. We also present our management of 19 patients, the largest case series to date, highlighting knowledge gaps surrounding the management of this salient pathology. METHODS: A literature search using PubMed and SCOPUS was conducted using the following search terms: (pediatric) AND (Cavum septum pellucidum) OR (cavum vergae) OR (cavum velum interpositum) AND (management). Eligibility criteria included peer-reviewed publication published in the last 10 years, pediatric population, cavum cyst, and English language. A retrospective search was conducted for all pediatric cavum cysts between 2013 and 2023 at our institution. Clinical and radiographic characteristics as well as intervention and outcome data were collected for both the scoping review and our cases. RESULTS: 330 total articles were populated using our search. 12 articles met our inclusion criteria. 41.7% (n = 5) of the articles were case series, 33.3% (n = 4) were case reports, 8.3% (n = 1) was a technical article, 8.3% (n = 1) was a systematic review, and 8.3% (n = 1) was a case questionnaire. Resolution of symptoms was noted in all articles of our scoping review, regardless of treatment modality. The average age in our case series was 9.84 years old and average age at diagnosis was 5.53 years old. 6 patients (31.6%) were female and 13 patients (68.4%) were male. 2 out of the 19 patients (10.5%) were surgically treated. CONCLUSION: There is no clear consensus on the management of cavum cysts. A prospective, multicenter study is needed to create standardized pediatric cyst management guidelines. The current thought is that surgical intervention should be saved for those patients with obstructive hydrocephalus and signs of intracranial hypertension.

Long-term outcome of surgically treated and conservatively managed Rathke cleft cysts.

OBJECTIVE: Rathke cleft cysts (RCC) are benign lesions of the sellar region that require surgical treatment in case of visual deterioration or progression of the cyst. However, the natural course is often stable and asymptomatic. We aimed to investigate the characteristics of patients with cyst progression during follow-up (FU) and to compare the natural history of patients with RCC with patients who underwent surgery. METHODS: Patients with an MR morphologic cystic sellar lesion classified as RCC between 04/2001 and 11/2020 were included. Functional outcomes, including ophthalmologic, endocrinologic, and MRI data, were retrospectively analyzed and compared between surgically treated patients, patients on a "watch and wait" strategy (WWS), and patients on a WWS who underwent secondary surgery due to cyst progression. RESULTS: One hundred forty patients (median age 42.8 years) with RCC on MRI were identified. 52/140 (37.1%) underwent primary surgery. Of 88 patients (62.9%) with initial WWS, 21 (23.9%) underwent surgery for secondary cyst progression. Patients on the WWS had significantly smaller cyst volumes (p = 0.0001) and fewer visual disturbances (p = 0.0004), but a similar rate of hormone deficiencies (p = 0.99) compared with surgically treated patients preoperatively. Postoperatively patients suffered significantly more often from hormone deficiencies than WWS patients (p = 0.001). Patients who switched to the surgical group were significantly more likely to have preoperative T1 hyperintense signals on MRI (p = 0.0001) and visual disturbances (p = 0.001) than patients with continuous WWS. Postoperatively, these patients suffered more frequently from new hormonal deficiencies (p = 0.001). Endocrine and ophthalmologic outcomes in patients with primary and secondary surgery were comparable. Multivariate analysis showed that WWS patients were at a higher risk of requiring surgery for cyst progression when perimetric deficits (p = 0.006), hyperprolactinemia (p = 0.003), and corticotropic deficits (p = 0.005) were present. CONCLUSION: Surgical treatment of RCC may cause new hormonal deficiencies, which are rare in the natural course. Therefore, the indication for surgery should be carefully evaluated. Hyperprolactinemia and corticotropic deficits were significant indicators for a secondary cyst progression in patients with RCC. However, a significant amount of almost 25% of initially conservatively managed cysts showed deterioration, necessary for surgical intervention.

Symptomatic infratentorial ependymal cyst arising from the medulla: a case report with review of literature.

BACKGROUND: Ependymal cysts (EC) typically present supra-tentorially near the lateral ventricle, juxta ventricular, or temporoparietal regions. Previous cases have also identified infratentorial EC of the brainstem, cerebellum, and subarachnoid spaces. They are mostly asymptomatic. In this paper, we present the first-ever case of a symptomatic medullary ependymal cyst treated with surgery, along with a comprehensive review of the literature on EC of other parts of the brain stem. CASE DESCRIPTION: This 51-year-old female presented with hearing loss, dizziness, diplopia, and ataxia. Radiographic imaging indicated the presence of a non-enhancing lesion in the medulla with a mass effect on the brainstem. Pathological examination confirmed its characterization as an ependymal cyst. The patient underwent a suboccipital craniotomy for the fenestration of the medullary ependymal cyst under neuro-navigation, Intra-op ultrasound and intra-operative neuro-monitoring. Histopathological examination confirmed the diagnosis of an ependymal cyst. At one month follow-up, her KPS is 90, ECOG PS 1, and her ataxia has improved with complete resolution of diplopia. CONCLUSION: Due to their rarity and potential similarity to other cystic structures, EC may be overlooked or incorrectly diagnosed resulting in mismanagement and surgical disaster. Therefore, a comprehensive understanding and awareness of their distinct characteristics are essential for accurate diagnosis and appropriate management.

Spontaneous and asymptomatic rupture of an RCC with resolution of symptoms.

There is no standard of care for management of Rathke cleft cysts (RCCs), and protocol for spontaneous rupture or residual capsule fragments is not well documented.Our case involves a Caucasian man in his 80s who presented with muscle weakness, fatigue, bitemporal hemianopia and pain. Further examination demonstrated decreased thyroid and cortisol levels. MRI revealed a 1.6×1.5×1.3 cm sellar homogenous mass with extension into the suprasellar cistern. While the size of the cyst was rather large, a decision was made to follow conservatively with serial MRI. At 3 years, the mass had spontaneously regressed. The patient was asymptomatic without imaging evidence of RCC recurrence at 4-year follow-up.Classic indications for surgical intervention in suprasellar cysts were subtle in our patient and his advanced age made us take a conservative approach. Current data are lacking regarding management of RCCs presenting with endocrine dysfunction. Our case suggests that RCCs presenting with endocrine dysfunction may be managed conservatively with serial imaging-based monitoring.

Measurement of the intersiphon distance for normal skull base development and estimation of the surgical window for the endoscopic transtuberculum approach in children.

OBJECTIVE: Due to the underdeveloped skull base in children, it is crucial to predict whether a sufficient surgical window for an endoscopic endonasal approach can be achieved. This study aimed to analyze the presumed surgical window through measurement of the intersiphon distance (ISD) and the planum-sella height (PSH) on the basis of age and its correlation with the actual surgical window for the endoscopic transtuberculum approach. METHODS: Twenty patients of each age from 3 to 18 years were included as the normal skull base population. ISD and PSH were measured and compared among consecutive ages. Additionally, 42 children with craniopharyngiomas or Rathke's cleft cysts who underwent treatment via the endoscopic transtuberculum approach were included. ISD and PSH were measured on preoperative images and then correlated with the dimensions of the surgical window on postoperative CT scans. The intraoperative endoscopic view was classified as narrow, intermediate, or wide based on operative photographs or videos, and relevant clinical factors were analyzed. RESULTS: In the normal skull base population, both ISD and the estimated area of the surgical window increased with age, particularly at 8 and 11 years old. On the other hand, PSH did not show an incremental pattern with age. Among the 42 children who underwent surgery, 24 had craniopharyngioma and 18 had Rathke's cleft cysts. ISD showed the strongest correlation with the actual area of the surgical window [r(40) = 0.69, p < 0.001] rather than with age or PSH. The visual grade of the intraoperative endoscopic view was narrow in 17 patients, intermediate in 21, and wide in 4. Preoperative ISD was 14.58 ± 1.29 mm in the narrow group, 16.13 ± 2.30 mm in the intermediate group, and 18.09 ± 3.43 mm in the wide group (p < 0.01). There were no differences in terms of extent of resection (p = 0.41); however, 2 patients in the narrow group had postoperative complications. CONCLUSIONS: Normal skull base development exhibited age-related growth. However, in children with suprasellar lesions, the measurement of the ISD showed a better correlation than age for predicting the surgical window for the endoscopic transtuberculum approach. Children with a small ISD should be approached with caution due to the limited surgical window.

Microsurgical Resection of a Pineal Cyst via a Paramedian Supracerebellar Infratentorial Approach.

Pineal cysts are typically detected in around 1.3% to 4.3% of patients during routine magnetic resonance imaging (MRI) scans.1,2 The vast majority of pineal cysts are benign, asymptomatic, and typically do not necessitate surgical intervention. Large pineal cysts are known to cause hydrocephalus with its associated symptoms and thus can require in rare cases surgical resection. Even in the absence of hydrocephalus, selected patients with large pineal cysts causing headaches and visual disturbances can find relief after surgical resection.3,4 The supracerebellar infratentorial (SCIT) approach is widely used and represents an extraparenchymatous approach through a natural corridor to the pineal region.5 Performing this approach in a semisitting position allows for an optimal retraction of the cerebellum by gravity. We employ a minimally invasive paramedian SCIT approach for the resection of pineal cysts. In our experience, the paramedian SCIT approach allows for a less steep operating angle and a smaller craniotomy compared with the midline SCIT approach. We present a 24-year-old female complaining of headache. The initial MRI was conducted 2 years before surgery. Following the initial evaluation, the patient experienced progressive headaches without neurologic deficits. A subsequent MRI revealed enlargement of the pineal cyst, leading to the indication for surgical resection. The surgery was performed mainly under the operating microscope with endoscopic visualization in suitable situations as our small approach restricts bimanual dissection with an endoscope. In our experience, this approach provides a versatile and minimally invasive access to the pineal region, making it optimally suitable for pineal cysts requiring surgical resection.