Classification of Headaches Associated with Rathke's Cleft Cyst According to Their Onset and Duration: A Clinical Study

Research Article

Austin Neurosurg Open Access. 2014;1(2): 1009.

Classification of Headaches Associated with Rathke's Cleft Cyst According to Their Onset and Duration: A Clinical Study

Yasuhiko Hayashi1*, Daisuke Kita1, Masayuki Iwato1, Issei Fukui1, Hiroki Sano1, Yutaka Hayashi1, Osamu Tachibana2 and Jun-ichiro Hamada1

1Department of Neurosurgery, Kanazawa University, Japan

2Department of Neurosurgery, Kanazawa Medical University, Japan

*Corresponding author: Yasuhiko Hayashi, Department of Neurosurgery, Graduate School of Medical Science, Kanazawa University, Address; 13-1, Takaramachi, Kanazawa, 920-8641, Japan

Received: March 05, 2014; Accepted: May 07, 2014; Published: May 08, 2014


Objective: Although Rathke cleft cysts (RCCs) are typically symptomatic, headaches can be one of the common symptoms, together with visual impairment and endocrinological abnormalities. Although several factors affecting the development of headache have been reported, the detailed mechanism are still unknown.

Methods: This retrospective study included 62 patient with RCCs whose symptom was headache and who were examined with using of magnetic resonance (MR) imaging, intraoperative findings, and pathology of surgical specimens.

Results: The characteristics of headache onset and duration were divided into three types. Apoplexy type headaches revealed hyper intensity on T1– weighted images (WI) and hypointensity on T2–WI of MRI. All patients with apoplexy characteristically had waxy nodules in their cysts, which showed as extreme hypointensities on T2–WI. Acute type headaches revealed hyper intensity on T1–WI with inconsistent intense signals on T2–WI. Chronic type headaches showed hypointensity on T1–WI in 12 patients (50%) and hyper intensity on T2–WI, similar to cerebrospinal fluid, and hyper intensity on T1–WI, with hyper intensity in 5 and hypointensity in 7 on T2–WI in the other 12 (50%). Cyst size was significantly large in chronic type. Pathological examination demonstrated that intracystic hemorrhage was dominant in apoplectic type. In chronic type headache, both infiltration of collagen tissue and inflammatory cells were characteristically detected.

Conclusion: In acute and apoplectic types, inflammation spread by cyst contents to the surrounding structures was suspected. Intracystic hemorrhage was also suggested as possible causes, particularly for apoplectic type headache. With respect to chronic type, two different mechanisms, mechanical compression and continuous infiltration of inflammatory cells were considered.

Keywords : Rathke cleft cyst; Headache; Magnetic resonance imaging; Pathology


CSF: Cerebrospinal Fluid; MR: Magnetic Resonance; RCC: Rathke Cleft Cyst


In recent years, using modern neuroimaging, Rathke cleft cysts (RCCs) have been detected as small, asymptomatic sellar lesions [1,2]. Although their incidence in normal autopsy reports is high (13 to 22%), RCCs rarely become symptomatic throughout life [3– 5]. As a result of the recognition of RCCs as distinct clinical entities, many studies have been conducted on the neuroradiological and pathological features of RCCs [2,6,7].

In many patients, RCCs are still detected incidentally without obvious clinical symptoms; on the other hand, RCCs occasionally manifest as characteristic symptoms, such as headache, visual impairment, and endocrinological abnormalities [2,7–9]. Although many authors have reported details about the identification of differential neuroimaging features of intra– and supra–sellar cystic mass lesions including RCC, there are still few reports about thecorrelation between clinical symptoms, neuroimaging features, and characteristics of cyst contents of RCCs [6,9–11]. Although it is apparent that it is clinically meaningful to compare and correlate the signal intensities of magnetic resonance (MR) images with the contents of RCCs, there are many exceptions to the correlations that do not follow the trends reported [12,13].

Headaches are well known to be a common presentation of RCCs and manifest in 44 to 59% of symptomatic patients with RCCs [12,14]. As headaches associated with RCCs have not been well characterized, they are not described in the International Classification of Headache Disorders, 2nd edition (ICHD–II) [14]. Moreover, there are few studies about the characteristics and underlying mechanisms that cause headache in the patients with RCCs. Thus, we wanted to investigate which factors lead to major clinical symptoms of RCCs by conducting a retrospective review of the neuroimaging and pathological studies of RCCs in our institute.

Clinical Materials and Methods

This retrospective study involved 91 patients presenting with RCCs in our institute between 1994 and 2012. Among them, 62 patients (68%) presented with headaches and other 29 patients (32%) presented with other symptoms or found incidentally. Among the 62 patients whose symptoms were headache, operations were performed in 43 patients and postoperative histological results were confirmed as RCC in 39 patients. All patients underwent MRI, and visual and endocrinological examinations. RCC size was evaluated using MRI, with or without gadolinium–enhanced T1–weighted images (WIs) on axial, coronal, and sagittal sections. The signal intensities of cystic contents on T1–and T2–WIs and the presence of waxy nodules (a non–enhanced intracystic nodule whose signals are hyper–intense on T1 and very hypo–intense on T2) were assessed.

A preoperative diagnosis of RCCs was made on the basis of the following MRI findings that are characteristic of RCCs; cystic lesions in the sellar or suprasellar region, absence or faint cystic wall enhancement, normal pituitary gland around the cyst, and absence of calcification. Moreover, intraoperative findings comparable to RCCs were considered when the cysts' contents were white or yellow, with varying viscosities of mutinous liquid and without any nodule of calcification. Postoperatively, final diagnosis was made using surgical specimens from 39 patients, with a light microscopic analysis demonstrating the pathological findings as follows; the epithelium lining consisted of the cyst wall with cubical or columnar cells, cilia on the cell surface inside the cyst, and goblet cells. Four patients were diagnosed using MRI and intraoperative findings only because of a lack of surgical specimen. Another 19 patients without surgical treatment were diagnosed by MRI findings only.

Headaches were divided into three types according to their onset and duration; apoplectic, headache with sudden onset manifesting like a pituitary apoplexy; acute, unusual episodic headache occurred within one month before consultation and patients remembered the onset clearly; and, chronic, headache persisted for more than a month and patients did not remember the onset clearly. The location and duration of headache was obtained from the patient records.

Chi–square and Post–hoc tests were used for comparison between two groups out of three. Chi–square test (two–tailed) was applied for when analyzing sex difference, T1–WI and T2–WI signals, the presence of endocrinological abnormalities, and pathological observations. Post–hoc test was applied when analyzing patients' ages and size of cysts. A p–value of <0.05 was considered statistically significant.


In our study, headache was the most common manifestation and occurred in 62 patients (68%). This cohort consisted of 17 males and 45 females, with an age at diagnosis ranging from 10 to 67 years (mean 34.2). Among these patients with headache, 11 (18%) presented with visual acuity and field disturbance, and 30 (48%) with endocrinological abnormalities. Meanwhile, 29 patients were diagnosed with RCC with symptoms other than headache. This cohort consisted of 11 males and 18 females, with an age range of 6 to 74 years (mean 40.9). In these patients, visual impairment was identified in 11 (38%), endocrinological abnormalities were found in 21 (72%), and other symptoms in 6 patients (21%) (Table 1).

Apoplectic type headaches were found in 15 patients (24%), 1male and 14 females, with an average age of 31.7 years. Their MRI findings were uniform in content, hyper intense on T1–WI and hypo intense on T2–WI. The average of maximum diameters in apoplectic type of RCCs was 15.3 mm. In particular, characteristic waxy nodules, showing marked hypointensity on T2–WI, were seen in all 15 patients (100%) (Table 1).

Acute type headaches were found in 23 patients (37%), 9 males and 14 females, with in average age of 34.3 years. Their MRI findings were hyper intense in uniform on T1–WI; however, hypo intense in 18 patients and hyper intense in 5 on T2–WI were found. Signal intensities of their cyst contents were regular in 14 patients and irregular in 9. The average of maximum diameters of this type was 14.6 mm, which was not statistically significant compared to cysts detected in apoplectic type (p=0.708). Waxy nodules were detected in 8 patients (35%) (Tables 1,3).

Chronic type headaches were found in 24 patients (39%), 7 males and 17 females, with an average age of 35.4 years. The MRI findings of their cyst contents could be divides into two groups. The first group (12 patients) showed hypointensity on T1–WI and hyper intensity on T2–WI, which was almost identical as cerebrospinal fluid (CSF). Intraoperatively, the cyst content of this group was observed as a clear fluid similar to CSF. The second group (also 12 patients) showed hyper intensity on T1–WI, and hypointensity, or hyper intensity on T2–WI, in 7 and 5 patients, respectively. Intraoperatively, the cyst content of this group was observed as a mutinous fluid with hyper viscosity. Signal intensities of their cyst contents were regular in 14 patients and irregular in 10. The average of maximum diameters of RCCs in this type was 19.5 mm, which was significantly larger than that from the other two types (p=0.0014 to apoplectic type and p<0.0001 to acute type, Post–hoc test). But the average of maximum diameters of RCCs between two groups of this type was not statistically significant (p=0.581, Post–hoc test). Waxy nodules were found only in 2 patients (8%) (Tables 1,3).

The location of the headaches was primarily in the frontal region (41 patients, 66%) regardless of the type of headache. Pain recognition in the retrobulbar region was detected and took a second place by 11 patients (18%), and following as occipital region in 5 (8%), temporalregion in 4 (6%), and parietal region in one (2%) (Tables 1,3).

Across all the patients, RCCs that were hypo intense on T1–WI and hyper intense on T2–WI (n = 12) had an average of maximum diameters of 20.6 mm in this type and fluid similar in appearance to CSF in the cysts, while RCCs that were hyper intense on T1–WI (n= 50) had an average of maximum cyst diameter of 15.3 mm and white⁄ yellow–colored, hyper viscous mutinous fluid within the cysts. The difference between the maximum cyst diameters of these two groups was statistically significant (p= 0.0008, Post–hoc test) (Tables 1,3).

Surgery was performed with procedures, such as aspiration of cyst content and partial resection of the cyst wall, in 43 out of 62 patients experiencing headaches. Among the 43 patients, 39 underwent transsphenoidal surgery and 4 underwent transcranial surgery. Of the patients who underwent transsphenoidal surgery, a microscope was used for 26 patients from 1994 to 2005, and an endoscope was used for 16 patients from 2006 to 2012. All transcranial surgeried were performed via the standard pterional approach (Table 1).

Pathological confirmation was obtained in 39 patients, and microscopic analysis was performed to assess the infiltration of collagen fibers, invasion of inflammatory cells (Figure 1), and intracystic hemorrhages (Figure 2). In apoplectic type headaches (surgical specimens from 10 patients), invasion of inflammatory cells was detected in 9 (90%), and intracystic hemorrhage in 6 (60%), whereas proliferation of collagen tissue was only found in 2 (20%). In all patients with acute type headache (surgical specimens obtained from 12 patients), invasion of inflammatory cells, and proliferation of collagen tissue was found in 6 cases (50%) and intracystic hemorrhage in only 2 (17%). In chronic type headache (surgical specimens from 17 patients), proliferation of collagen tissue was observed in 16 (94%) and invasion of inflammatory cells in 10 (59%), whereas, intracystic hemorrhage was observed in only in 1 (6%) (Tables 2,3). Characteristic observations of intracystic hemorrhage were found in intracystic granulation tissue beneath the epithelial cells (Figure 2).