Abstract
Introduction
Rathke's cleft cysts are a relatively common finding at autopsy, and are being detected with increased frequency during life by CT and MRI scans (1, 2). These typically intrasellar lesions are usually asymptomatic and thus most commonly represent an incidental finding. However, Rathke's cleft cysts may be a cause of secondary headache, a fact that is not universally appreciated. Although the features of Rathke's cleft cysts are well described in the endocrinological and neuroradiological literature, there is a dearth of information related to the clinical presentation of these lesions in the headache literature. We present a case of secondary headache due to such a lesion.
Case report
A 17-year-old white male developed difficulty concentrating, memory disturbance and intermittent headaches. The headache was variable in location, lasted several hours and recurred every 2–3 days. He subsequently developed difficulty sleeping and was evaluated in a sleep laboratory. Based on the clinical examination and an overnight sleep study he was felt initially to have left-sided occipital neuralgia, delayed sleep phase syndrome and possibly periodic leg movements of sleep.
He was advised to use acetaminophen for the headaches, zolpidem for sleep and various medications for the periodic leg movements.
His symptoms persisted and the headaches worsened. He complained of a constant holocranial headache with superimposed sharp mid-occipital pain. The diagnosis was changed to ‘cervicogenic headache’ and he was given carisoprodol and suboccipital injections of a local anaesthetic, measures that were also ineffective. The headaches continued and over the ensuing years were ascribed to ‘stress’ or ‘cervical spine dysfunction’. Sometimes the headaches would escalate to an ‘exploding’ type, with nausea, photophobia and phonophobia. Occipital nerve blocks, acupuncture and Rolfing were attempted, all without success.
Numerous medications for periodic leg movements of sleep, headache and later depression were also tried, including bupropion, valproate, ropinerole, pramipexole, carbidopa/levodopa, celocoxib and SSRI's. All were either poorly tolerated and/or ineffective in eradicating the pain. Injections of botulinum toxin were considered.
MRI studies of the brain performed elsewhere in 1997 and 1999 were read as normal, as was a brain SPECT scan, apparently obtained because of the refractory nature of the patient's symptoms. Rolfing continued and he was diagnosed with ‘chronic fatigue syndrome’. He developed decreased libido and erectile dysfunction. His college work suffered as a result of his illness and he became unable to pursue his academic responsibilities.
When first seen at our institution at the age of 21 he continued to have the same complaints, as well as blurred vision. He had a constant holocranial ‘pressure’ headache, ‘cloudy’ mentation and tightness in his neck and shoulders. Superimposed on this background were intermittent exacerbations of right hemicranial or posterior sharp and throbbing pains, lasting for a few hours, occurring several times per week. He was taking daily naproxen sodium for headache relief and an oral caffeine preparation to combat drowsiness. He had a history of motion sickness and a tendency for cold hands and feet. There was a possible history of migraine in his mother.
Review of his brain MRIs suggested a cystic abnormality in the region of the pituitary. The radiologist at our institution described ‘A small mass in the suprasellar region just anterior to the infundibulum. The mass nestles up against the inferior portion of the optic chiasm superiorly, and seems to be in contact with the pituitary gland inferiorly. It is rounded and homogeneous. On both studies, there is a small amount of enhancement in the periphery’. There was judged to have been no change between the 1997 and 1999 studies.
As attempts at outpatient therapy were not relieving his symptoms, he was admitted to the hospital for repetitive intravenous metoclopramide and dihydroegotamine therapy. This was also ineffective.
Because of the abnormality observed on MRI, an endocrinological work-up was initiated. This revealed a modestly elevated prolactin level (41.3 ng/ml, normal = 4.1–18.4), and borderline low testosterone (264 ng/dL, normal = 240–820). Thyroid function studies (T4 7.3 mcg/dL, normal = 4–10; Tuptake 0.97, normal = 0.69–1.11; FTI 7.1, normal = 3.5–8.8, TSH 2.80 mcIU/ml, normal = 0.35–5.50) and a somatomedin-C level (208 ng/ml, normal = 182–780 ng/ml) were normal. A corticotropin stimulation test was normal showing a post-stimulation serum cortisol value of 29.9 mcg/dL. Formal visual field testing was normal. Repeat brain MRI (Fig. 1) again demonstrated a non-enhancing 1-cm mass just anterior to the pituitary that had expanded the sella. The lesion showed low signal on T1 images, with high signal on T2.
MRI demonstrating 1 cm mass anterior to the pituitary.
A neurosurgical consultation was obtained. Transsphenoidal resection was undertaken with the finding of a cystic mass in the sella turcica typical of a Rathke's cleft cyst. There were no surgical complications. Within 3 months his chronic daily headaches had resolved and his energy had improved. His prolactin level normalized (14.5 ng/ml) but his testosterone level failed to rise (2.59 ng/ml, new normal=2.8–8.0). He resumed his academic endeavours and is currently being treated with amitriptyline (for sleep) and testosterone replacement.
Discussion
Rathke's cleft cysts are included in the differential diagnosis of sellar and suprasellar lesions along with craniopharyngiomas, arachnoid cysts and pituitary adenomas (3, 4). The precise origin of Rathke's cleft cysts is uncertain but they may derive from remnants of Rathke's pouch, thus sharing a similar origin with craniopharyngioma (1). Rathke's cleft cysts are benign lesions composed of cysts lined with columnar or cuboidal cells, and sometimes harbouring Goblet cells and cilia (3). The fluid within the cyst is of variable composition and may resemble CSF or be mucoid, yellow and grumous (5). Unlike craniopharyngiomas, Rathke's cleft cysts uncommonly contain calcifications (3, 5). While primarily an intrasellar lesion, suprasellar extension may occur. Occasionally the cyst occurs exclusively in a suprasellar location where it may compress the optic chiasm or compromize third ventricular outflow of CSF (4).
When symptomatic, Rathke's cleft cysts most commonly cause headaches (1) that may occur as an isolated complaint or in association with endocrinological and ophthalmological disturbances. The headaches are often bifrontal or frontotemporal and may be progressive, with throbbing and retro-orbital pain (5). Bitemporal field cuts may occur due to compromize of the optic chiasm and blurred vision could occur due to hydrocephalus (6). Endocrinological abnormalities may include menstrual disturbances, decreased libido, impotence, hyperprolactinemia, galactorrhea and diabetes insipidus (5). Interestingly, mental status changes are more suggestive of craniopharyngioma (5).
While imaging studies may suggest the diagnosis of Rathke's cleft cyst, definitive diagnosis rests on an examination of the histology of the cyst wall. Treatment consists of excision of the lesion to the fullest extent possible. The transnasal transsphenoidal approach has been advocated as preferable to craniotomy in order to prevent leakage of the cyst contents into the CSF (3, 4). Surgery usually improves the neurological and ophthalmological symptoms, but endocrinological abnormailities often do not improve or may even worsen (5).
Mass lesions that expand the sella turcica may be associated with hyperprolactinemia even though the lesions themselves do not directly secrete this hormone (6). In such cases, an increase in intrasellar pressure, or direct compression of the pituitary stalk, is postulated to impair pituitary portal blood flow. This compromizes the delivery of dopamine, the hypothalamic prolactin inhibitory factor and potentially other hypothalamic hormones to the pituitary gland, resulting in a mildly increased prolactin level and variable manifestations of hypopituitarism, as seen in our patient. A recent study by Arafah et al. (6) has demonstrated that in the case of pituitary adenomas such increases in prolactin levels correlate with increased intrasellar pressure, and this in turn with the symptom of headache. We suggest that a similar phenomenon occurs in patients with Rathke's cleft cysts who experience intractable headache and manifest hyperprolactinemia and other endocrinological abnormalities. Such patients should strongly be considered for surgery.