Clinical manifestations

Presentation and course

Patients with colloid cysts most commonly present with one of three symptom complexes: (1) headache, papilledema, and occasionally false localizing focal, motor, and sensory signs; (2) progressive or fluctuating dementia with or without headache and raised intracranial pressure; or (3) paroxysmal severe headaches, nausea, vomiting, stupor, or coma without symptomatology between episodes (39; 86; 50; 83). Individually, headaches are by far the most common symptom (89%), followed by nausea/vomiting (23%), visual decline (22%), dizziness/ataxia (20%), and cognitive decline (14%) (06). Unlike other brain tumors, headache associated with colloid cyst may resolve or reduce in the supine position (76). Asymptomatic/incidental cysts are most often seen following trauma (06). Untreated patients can develop fatal colloid cysts that may present with acute disturbances of consciousness, coma, and death because of ventricular outflow obstruction with resultant obstructive hydrocephalus (39; 50; 15; 43; 19; 73). Subarachnoid hemorrhage into the colloid cyst can occur, and such patients can manifest with a change in clinical symptoms and an increase in the cyst size (58; 25). Some patients with colloid cyst may present following head trauma with massive hydrocephalus, requiring emergent shunt placement (18). Colloid cysts can present with some intraocular findings other than papilledema. For example, one report noted visual field deficits and findings suggestive of glaucoma (62), although another reported intraocular hemorrhage (08).

Episodic positional headaches suggest that the colloid cyst moves in and out of the foramen of Monro on its pedicle with intermittent obstruction of cerebrospinal fluid. Most headaches, however, are not positional in nature (14; 43). Neuropsychiatric symptomatology is highly prevalent in patients with colloid cyst and can range from antegrade amnesia to gustatory hallucination (46). These symptoms can occur in isolation or in association with hydrocephalus. The neurocognitive symptoms reflect altered function due to compression of the adjacent hypothalamus and subcortical limbic regions (67). Although psychiatric symptoms are common in these patients, it is an uncommon reason for referral for neurosurgical evaluation. Depression, anxiety attacks, paranoid ideation, memory difficulties, and decreased cognition are observed occasionally and are often subtle. Sometimes surgical cyst removal, even in the absence of hydrocephalus, can ameliorate these symptoms (51).

Prognosis and complications

Colloid cysts can produce chronically elevated intracranial pressure, which, if left unattended, may eventually lead to serious complications such as visual loss and memory difficulties. Sudden interruption of cerebrospinal fluid circulation through ventricular outflow obstruction may also occur, possibly resulting in coma and even sudden death (20; 54; 50; 14). In one series that collected patients between 1984 and 1995, almost 15% of patients were admitted in a comatose state, and 5% died suddenly (53). The overwhelming majority of patients with rapid deterioration (96%) have cyst diameter greater than 1 cm, and adults are more likely to present to care with less than 24 hours of symptoms (43). Although acute neurologic deterioration has been emphasized, most patients present with long-standing, intractable symptoms that allow for diagnosis and elective surgery. Asymptomatic, incidentally discovered colloid cysts rarely cause acute hydrocephalus or sudden neurologic deterioration in the absence of trauma (06). High risk factors predicting need for prompt treatment (vs. observation) include diameter greater than 7 mm, older age, FLAIR hyperintensity within lesion, presence of headaches, and location within anterior or posterior regions of the third ventricle (06; 87; 83).

Clinical vignette

The patient was a 36-year-old, right-handed, Caucasian woman who had an abrupt onset of severe headache while bending forward during intense household work. The headache prevented her from activities, and while walking to her bed to lie down, she collapsed to the floor. She was taken to the emergency room for evaluation. On examination, she was found to be stuporous with intact brainstem reflexes. An urgent CT scan of the brain was performed that demonstrated a hyperdense cystic lesion of the third ventricle with obstructive hydrocephalus. The clinical and neuroimaging findings were felt to be compatible with colloid cyst of the third ventricle. She underwent emergent ventriculostomy for acute hydrocephalus. Subsequently, she was taken to the operating room for more definitive therapy consisting of endoscopic evacuation of cyst contents and microsurgical resection of cyst capsule. Thick tenacious material was aspirated from the cyst. Postoperative recovery was gradual but complete, with no discernible neurologic deficits. She was able to return to her usual activities, and follow-up scan of her brain did not demonstrate any residual lesion or hydrocephalus.

Biological basis

Etiology and pathogenesis

The etiology of colloid cyst is unknown because most cases tend to occur sporadically (13). The reports of familial colloid cysts in 40 families that involved 83 patients have been published in literature (29). These case reports support the growing evidence for the possibility of genetic predisposition in the development of colloid cyst (44; 61). Although there is no consensus on the precise pattern of the genetic predisposition of colloid cyst, some authors postulate an autosomal dominant pattern of occurrence (07), although others argue that an autosomal recessive pattern is more plausible (75), and there are authors who posit that the inheritance is probably multifactorial (77). A large prospective clinical case series analyzed 13 families with their first-degree relatives affected with colloid cyst (26 patients) and reported an estimated familiar colloid cyst rate of 3.4% (29). The early diagnosis of first-degree relatives with colloid cyst is advised because of the higher risk of symptomatic lesions (61.5% to 89.5%) and mortality (7.7% to 12.3%) compared with those without a family history (29). The first-degree relatives of patients with colloid cysts, who develop symptoms suggestive of raised intracranial pressure should probably be evaluated with MRI screening, and genetic screening is recommended for monozygotic twins (13; 44).

Colloid cysts are smooth, spherical masses that arise in the anterior and dorsal regions of the roof of the third ventricle. The wall is a thin membrane enclosing a soft gray proteinaceous material or a dense hyaline substance.

The state of the cyst contents varies with the degree of hydration, from thick fluid to a solid gel, and this variation in turn affects the appearance on neuroimaging studies. The wall is composed of fibrous connective tissue lined by benign columnar ciliated epithelial cells (27). Although generally regarded as a malformation, the lineage of colloid cysts remains controversial. A neuroectodermal derivation for colloid cysts has been assumed based on structural and embryological considerations as well as their intraventricular location. Potential precursors include choroid plexus, ependyma, primitive neuroectoderm, and the paraphysis. Uncertainty over the specific nature of epithelium lining colloid cysts is reflected in the all-encompassing synonym "neuroepithelial cyst" that is often applied (41). Two immunohistochemical studies using histologic antigens and monoclonal antibodies indicated that colloid cyst epithelium is immunohistochemically different from that of normal or neoplastic choroid plexus. In 1, the immunophenotype of colloid cysts was similar to foregut-derived epithelia of enteric and Rathke pouch cysts, supporting endodermal origin for these cysts (42). This observation was further supported by studies on the nature of the cyst contents themselves. These studies indicate that the carbohydrate epitopes exhibited by cysts and their contents are also consistent with an endodermal origin (82).

Epidemiology

Colloid cysts of the third ventricle represent approximately 0.5% to 1% of primary intracranial mass lesions (Ahmed and Stanworth 2002; 21). There is no sexual predominance. The incidence of colloid cysts of the third ventricle is estimated to be 3.2 per 1 million persons annually (35). However, data from a systematic review of brain MRI findings reported a prevalence of 2 of 15,559 of incidental colloid cysts (56), and another population-based study of the brain MRI of 5800 patients in the Netherlands estimated the prevalence of colloid cysts as 1 of 5800 (09). Although colloid cysts are congenital lesions, they usually remain asymptomatic until 20 to 50 years of age; the symptomatic lesions are less common in children, but reports from case series of affected children suggest that they tend to have more aggressive clinical features and rapid neurologic deterioration compared to adults (30; 81).

Prevention

There are no preventive measures that decrease the occurrence of colloid cysts.

Differential diagnosis

Confusing conditions

The differential diagnosis includes any third ventricular mass, including choroid plexus papillomas, glial tumors, metastases, craniopharyngioma, granuloma, hematomas, basilar artery aneurysms and, rarely, suprasellar pituitary adenomas. Metastatic lesion to choroid plexus may resemble colloid cyst, especially solitary lesion without other intracranial metastases. There appears to be an increased tendency for renal cell carcinomas to metastasize to the choroid plexus (47). The spherical shape of the tumor and its characteristic intraventricular location at the foramen of Monro, however, strongly suggest the diagnosis. Colloid cysts can often be definitively diagnosed based on clinical and radiographic studies (27; 64).

Associated or underlying disorders

Colloid cysts are usually associated with hydrocephalus, and patient with bilateral lateral ventriculomegaly should be properly evaluated to confirm or exclude colloid cyst of the third ventricle.

Diagnostic workup

The diagnosis of colloid cysts can be made definitively with CT or MRI in most cases. On CT scanning, colloid cysts appear as a distinctive isodense or hyperdense lesion at the foramen of Monro; variable contrast enhancement is noted (27; 12).

A distinctive MR appearance with high signal intensities noted on both T1- and T2-weighted images reflects the high protein content of the viscous cyst material (40). In cases where some of the cyst contents are solid, there is a variable radiographic appearance.

Solid areas appear on CT scans as markedly increased density, and signal intensity is increased on T1- and T2-weighted MRIs (80). Because some colloid cysts are isointense to brain on MRI and do not enhance, they may be more easily appreciated with CT (52).

Management

Colloid cysts are curable, yet potentially fatal, and the management is both challenging and controversial (38). The treatment goals for symptomatic colloid cysts should be relieving cerebrospinal fluid blockage caused by foraminal obstruction and removing the space-occupying lesion. Each case must be considered individually for surgical intervention. The risk of sudden death, albeit low, argues for surgical treatment in all patients with symptoms, particularly hydrocephalus.

There is no clear guidance on the management of incidentally diagnosed colloid cyst (11). Although these lesions can remain the same size for many years, there is a 5% to 15% risk of progression within 5 years of initial diagnosis of incidental colloid cysts managed nonoperatively (17). Close observation with serial neuroimaging studies may be a safe management strategy in some patients with incidentally discovered colloid cysts, in particular those that are low risk (no evidence of hydrocephalus, less than 7 mm diameter, young patient, location in mid-portion of third ventricle) (64; 06). In order to facilitate rational decision making in asymptomatic patients, a risk stratification system (modified Colloid Cyst Risk Score) was devised based on the age, gender, T2W FLAIR signal intensity within the lesion, extent of hydrocephalus, cyst size, and location (11). The total potential score is 8; patients with a score lower than 4 can be managed conservatively, whereas patients with score greater than 7 are at risk of symptomatic progression and should be evaluated for surgery. Conservative management of asymptomatic colloid cysts is a viable option. There are six case reports of patients managed with serial neuroimaging who subsequently had spontaneous regression of their lesions in the literature (28; 63; 79; 17; 57; 48). Turel and colleagues suggested that patients with an asymptomatic colloid cyst that is less than 10 mm should have an initial follow up image 6 to 12 months after diagnosis, and subsequent serial follow-up neuroimaging should be done every year (79).

Present management options for symptomatic colloid cysts include management of hydrocephalus and resection of the intraventricular mass. For patients presenting with symptomatic ventriculomegaly, placement of an emergent external ventricular drain may be required in the acute setting prior to cyst resection. Hydrocephalus persisting after surgical resection of cysts is typically treated with a ventriculoperitoneal shunt. Resection of intraventricular colloid cysts is most commonly performed via microsurgical (transcortical-transventricular or interhemispheric-transventricular) or endoscopic approaches with very low mortality rates (0.6% to 1.4%) (21; 60; 16). There is no consensus on which of both surgical techniques is superior for the treatment of colloid cysts (16; 70; 69). Data suggest that microsurgical approaches afford a higher rate of complete removal and a lower recurrence rate compared to endoscopic treatment (33; 23; 69). In a meta-analysis that compared the outcomes of 1278 patients treated with either approach, those treated with microsurgery had a higher incidence of complete surgical resection (97% vs. 58%) and lower recurrent rate (0.38% vs. 3%) relative to endoscopic treatment (72). Similarly, another meta-analysis reported a higher gross total resection rate (98.15% vs. 91.29%) and lower recurrent rate (0.00% vs. 1.78%) for the microsurgical approach compared to endoscopic surgical treatment (69). Although the patients treated with the endoscopic approach may not achieve complete resection of the tumor capsule, most of the patients have a generally lower outcomes in the long term (84; 36). In addition, the endoscopic approach is now assuming a standard front-line surgical option for the treatment of colloid cysts because of the significantly reduced rate of perioperative morbidity and lower cost (70; 05), and it has also decreased the rate of seizures (15% in microsurgery vs. 5% in endoscopic) and readmission rates (72; 16). Furthermore, both the operative time and length of hospital stay are reduced significantly with endoscopic resection (32; 24; 69). Refinements in technical expertise and instrumentation have made the endoscopic technique an efficient surgical option even for large (greater than 20 mm) and giant (greater than 30 mm) colloid cysts (04).

Conversion from endoscopic to microsurgical resection has also been reported (60; 84). One study demonstrated that microsurgical resection of colloid cysts led to a sustained improvement in neurocognitive function, presumably due to reduction of hydrocephalus and/or reduction of mass effect on the fornix (67). Morbidity and mortality include intraoperative bleeding, postoperative hydrocephalus, cerebrospinal fluid leak, subdural hematoma, cognitive deficits, seizures, and transient and permanent memory disturbances (74; 37; 78; 59; 22; 02; 14; 38). The amnestic syndrome is caused by bilateral fornix damage; sparing of the left fornix alone is sufficient to ensure a more favorable outcome (55). Clinical and radiological follow up are necessary to assess and assure lesion-free survival (49; 31; 34).

Special considerations

Pregnancy

There can be a sudden increase in the size of colloid cyst leading to acute hydrocephalus in pregnancy. Therefore, patients with asymptomatic colloid cyst of the third ventricle who desire pregnancy should be monitored closely (26).

Anesthesia

The management of a patient with an asymptomatic colloid cyst who is being evaluated for operation due to another surgical pathology requires special anesthetic considerations. Anesthesia can change CSF pressure, which may precipitate acute hydrocephalus. However, epidural anesthesia minimizes pain and has the least risk of fluctuation in CSF pressure (66).