Clinical manifestations

Presentation and course

The clinical manifestations of arachnoid cysts are nonspecific and depend on their location along the neuraxis as well as the age at presentation. The majority of arachnoid cysts are intracranial, and they are noted on 1% to 2% of brain MRIs (26; 71; 02; 49). Most arachnoid cysts are asymptomatic and identified incidentally. Intracranial arachnoid cysts most frequently arise in the middle cranial fossa (34%), retrocerebellar region (33%), and cerebral convexity (14%), but they can occur anywhere from within the ventricles to the interhemispheric space (02). Midline cysts tend to present earlier in life with signs and symptoms of hydrocephalus (03). Most cysts are solitary. Only 2% to 5% of patients have multiple cysts, which are often noted in the context of genetic disorders (02). Most importantly, bitemporal arachnoid cysts occur in association with glutaric aciduria type 1 in up to 25% of cases. Urine should be checked for glutaric acid in cases of bitemporal arachnoid cysts, as general anesthesia can exacerbate metabolic derangements and, thus, pose significant risk of harm with surgeries (36).

Table 1. Clinical Characteristics of Intracranial Arachnoid Cysts in Children and Adults

There is a clear difference in the rate of symptomatic presentation and the type of symptoms children and adults exhibit. Most arachnoid cysts are discovered incidentally for general symptoms most commonly evaluated in the population, such as headaches.

In children, about 28% of these cysts do have symptoms attributed to them, which are usually sequelae of elevated intracranial pressure, such as headaches, macrocephaly, or intractable emesis. A particularly intriguing presentation in children is "bobblehead doll syndrome." This occurs in suprasellar arachnoid cysts and consists of a head-bobbing motion due to neck tremor, typically in the context of intraventricular CSF flow obstruction. About 70% of bobblehead doll syndrome cases are caused by suprasellar or third ventricular cysts (52).

Endocrine abnormalities, such as precocious puberty and growth hormone deficiency, may be seen in children both at presentation and on follow-up. In a pediatric cohort of 44 mainly symptomatic patients, three had precocious puberty, and one had amenorrhea at presentation. Long-term follow-up of this cohort revealed new endocrinopathies in 38% of the patients who underwent operation and 25% of those who did not. Besides precocious puberty, growth hormone deficiency was the most common abnormality (33).

A significant proportion of children are diagnosed with arachnoid cyst while undergoing epilepsy evaluation (23). It is contentious whether arachnoid cysts actually cause seizures or are simply a "flag" that there is some coexisting process in the underlying brain (eg, hypoplasia). Nevertheless, the presence of an abnormal co-localizing ictal or interictal EEG or imaging, such as hypoperfusion or hypometabolism, will often influence the decision to treat surgically (68).

In adults, the rate of symptomatic cysts is about 3.5 times lower than in children. Besides headache evaluations, incidental cysts are discovered during stroke or transient ischemic attack, vertigo or tinnitus, and, less commonly, seizure evaluations (23). They may also be discovered after traumatic injuries, such as those associated with motor vehicle accidents. The main difference in symptomatic presentation in adults compared to children is the higher prevalence of cranial nerve dysfunction in adults (39%), which is usually linked to posterior fossa location. Subtle cognitive deficits may be identified in patients with left temporal arachnoid cysts (75). A preoperative case-control study found that patients with arachnoid cysts had more neurocognitive deficits on tests of verbal fluency and the Tower test than a control group admitted for spinal surgery; postoperatively, improvements were only seen in the group with arachnoid cysts (22). Similar findings were described in another series of 22 patients, with depression and anxiety being overrepresented in the arachnoid cyst population and with symptomatic improvement after shunting (21). There are numerous case reports linking psychosis to the presence of arachnoid cysts (06). This may be merely coincidental with the relatively high prevalence of both psychiatric illness and arachnoid cysts, and the frequent central nervous imaging of patients with psychiatric or neurologic symptoms.

Spinal arachnoid cysts may be intradural or extradural. The symptoms from spinal arachnoid cysts are progressive lower limb weakness, spasticity, radicular pain, scoliosis, and recurrent urinary tract infection. Cases with acute presentations or intermittent symptoms and signs are well described (76). In general, children with spinal arachnoid cysts present with motor deficit (76%), although 25% had back pain only (16).

Intraneural arachnoid cysts situated within the sheath of cranial nerves are an extremely rare manifestation described in the context of cranial nerve palsy (09).

Prognosis and complications

The observed natural history of arachnoid cysts differs significantly between children (especially infants) and adults. These age group differences are most likely the combined result of concurrent brain growth, cyst locations that may lead to earlier symptom development, and cyst resolution in children versus a higher incidence of unrelated comorbidities prompting brain-imaging and de novo cyst development later in life for adults.

In children, a study evaluating patients aged five years or younger found that 80% of significant arachnoid cyst enlargement happens in the first year of life, and no cyst expansions are noted in the 3- to 5-year-old group (32). Similar observations were made by another pediatric natural history study showing a lack of cases with enlargement beyond age four years (02). These findings link the most rapid postnatal brain growth phase to cyst enlargement. Longitudinally, these studies showed stable lesion size in most patients and a 10% to 23% risk for cyst enlargement, but also potential for cyst regression, in 4% to 10% of patients (32; 02). The latter might explain the decreasing prevalence of arachnoid cysts with age in both pediatric and adult cohorts (71; 32; 02).

In adults, untreated asymptomatic arachnoid cysts have a very low enlargement potential. In two natural history studies with average follow-up periods of 2.5 to 4 years, 95% to 97% of cysts remained stable in size, and 0% to 2.3% enlarged, whereas 1% to 5% reduced in volume or even resolved completely (02; 23). Case series on resolution of arachnoid cysts clearly indicated a much lesser potential for resolution in adults and patients with larger cysts (57). Care should be taken when attributing a patient's symptoms to the presence of the cyst, which is often a matter of debate. Extrapolating from the natural history data, the risk of symptom development is less than 0.25% per year in adults (02; 23). There may be rupture of bridging veins or vessels in the cyst wall, which can result in a subdural hematoma or bleeding into the cyst (56; 60). Chronic hematomas are found in approximately 5% of patients with an arachnoid cyst (74). It has been estimated that arachnoid cysts are present in 2.5% of patients with chronic subdural hematomas (44). A case-control study found larger cyst size (greater than 5 cm) and head injury to be significant risk factors for cyst rupture or hemorrhage, although these hematomas may occur spontaneously as well (13). In these instances of arachnoid cysts associated with extra-axial hematoma, it may be sufficient to surgically address the hematoma without resecting the arachnoid cyst if there are no symptoms specifically associated with the cyst itself (79). From a series of 60 cases of middle cranial fossa arachnoid cysts treated by various measures, it appears that small effusions can be treated conservatively, and in cases in which surgical intervention is considered necessary, burr hole and subdural drainage are effective in most cases (64). Cyst-related mortalities are extremely rare (47).

Clinical vignette

A 61-year-old obese male presented with a 2-month history of episodic lightheadedness and mild headache. Lightheaded episodes lasted 5 to 10 minutes and could occur up to three to four times per day. On examination, there were no neurologic signs except for a moderately elevated blood pressure of 180/100 and grade 2 hypertensive changes on fundoscopy.

Investigations. A brain MRI without contrast showed a 3 to 4 cm left middle cranial fossa arachnoid cyst without mass effect. Urea and electrolytes, liver function, thyroid function, full blood count, and erythrocyte sedimentation rate were normal. The ECG met voltage criteria for hypertension. An EEG was normal, and a 24-hour EEG was normal, despite one symptomatic episode. Lumbar puncture found normal pressure and constituents. Repeated blood pressure measurements showed diastolic recordings of up to 120 mm/Hg. A chest x-ray was normal. Further investigation of hypertension did not reveal any cause.

Outcome. The patient began hypertension treatment with a beta-blocker, and he had resolution of his headaches and lightheadedness within 24 hours. No symptoms were present at the follow-up three months later. No intervention was performed to address the arachnoid cyst as the patient’s symptoms responded to medical management of his hypertension.

Biological basis

Etiology and pathogenesis

Most arachnoid cysts are developmental, and their exact etiology is unknown, but they can also be acquired after trauma or infection through CSF entrapment within arachnoid adhesions. The developmental hypothesis is corroborated by cysts identified on routine prenatal sonography (14). Cases followed from infancy have shown no hypoplasia at birth but, instead, the development of hypoplasia and expansion of the cyst with the passage of time (43). Some electron microscopy studies demonstrate that the inner sheath is composed of several layers of arachnoid cells, with underlying connective tissue rich in desmosomes and tight junctions as well as intermixed collagen fibers and myofibrils (40). However, an electron microscopic study of 24 symptomatic arachnoid cysts from different sites showed that the cyst walls varied in structure, with some composed of normal arachnoid (50%), some composed of a core of dense fibrous material with simple epithelial lining, and others with nonarachnoid luminal epithelium with microvilli and cilia (eg, ependyma), cilia, and nervous tissue, suggesting formation at early embryonal development as a teratological phenomenon (50).

A number of hypotheses explain the formation or expansion of arachnoid cysts. These include (1) cystic trapping of fluid due to the hypoplasia of adjacent brain; (2) an osmotic gradient caused by microhemorrhages drawing fluid into the cyst; (3) a slit valve mechanism causing unidirectional CSF flow into the cyst driven by brain pulsation, coughing, or Valsalva maneuver; or (4) active CSF secretion by ependymal-like cells into the cyst (07).

Secondary arachnoid cysts can occur after epidural anesthesia, overdrainage of CSF via ventriculoperitoneal shunts, spinal injury or surgery (27), head trauma or radiosurgery (41), craniotomy (37), phenol injection (54), or use of oil-based contrast media (62). Of the 17 neonatal cases of anterior cervical arachnoid cysts reported in the literature, 65% have had either prior myelomeningocele repair or a history of spinal trauma (25). There have been cases of cervicothoracic arachnoid cysts associated with obstetric brachial plexus palsy (39). Epidural spinal arachnoid cysts occur through small dural defects, in much the same manner as secondary arachnoid cysts.

The direct link between supratentorial arachnoid cysts in epileptogenesis is debated. The literature suggests inconsistent localization with epileptic foci on EEG (05; 77); however, there are cases where the epileptic foci colocalize with the arachnoid cyst, and cyst resection leads to resolution of seizures (11).

Epidemiology

Arachnoid cysts are identified in any age group, from routine prenatal sonography (14) to diagnostic imaging in older adults (71). The exact prevalence of arachnoid cysts is unknown. In large-scale prevalence studies on brain MRIs, arachnoid cysts were noted in 2.2% of the pediatric patients (26), 1.1% in the older adults (71), and 1.4% in the general adult population (02). In children, arachnoid cysts are twice as common in boys (03) but appear to have a more even sex distribution in the elderly (78). Temporal lobe cysts are more commonly found on the left side (2.5:1), and there seems to be a significant male preponderance of temporal arachnoid cysts (p< 0.004). For all other sites, there does not appear to be any sex predilection, apart from the cerebellar pontine angle, which may be more common in women (24).

A few genetic syndromes predispose to arachnoid cysts. Perhaps the clinically most important of these is glutaric aciduria type 1, which, if undetected, can pose a life-threatening risk in the context of general anesthesia (36). Other syndromes include spinal extradural arachnoid cysts, which may rarely be familial and associated with lymphedema-distichiasis syndrome and FOXC2 mutations; furthermore, arachnoid cysts in the brain are also more common in patients with tuberous sclerosis (5.5% vs. 0.5% general population) (42; 08). Intraspinal arachnoid cysts are commonly associated with other congenital abnormalities (48).

It has also been reported that arachnoid cysts can occur after stereotactic radiosurgery. These arachnoid cysts are extratumoral and can arise following treatment. They are histologically different from intratumoral cysts that form secondary to hemorrhagic change within the tumor (41).

Prevention

There is no known specific method to prevent or even indicate the need to prevent arachnoid cysts, even in the secondary (posttraumatic or inflammatory) setting.

Differential diagnosis

Confusing conditions

The clinical differential diagnoses of symptomatic intracranial arachnoid cysts include other causes of increased intracranial pressure, headaches, or cranial nerve palsy. Radiographic differential diagnoses include any cystic intracranial lesion, such as epidermoid cyst, subdural hygroma or chronic subdural hemorrhage, cystic neoplasms such as pleomorphic xanthoastrocytoma and hemangiopericytoma, and non-neoplastic cysts, like porencephalic, neurenteric or neuroglial cysts, expanded Virchow-Robin spaces and neurocysticercosis and brain abscesses.

In the spinal canal, the differential diagnosis includes any other cause of cord or root compression, such as a tumor (particularly ependymoma or hemangioblastoma), hematoma, infection, disc herniation, spinal epidermoid cyst, spinal dermoid cyst, spinal endodermal cyst, spinal hydatid cyst, and spinal cysticercosis. In the sacral region, the differential diagnosis includes meningoceles or secretory cysts of the nerve root pockets (eg, Tarlov cysts).

Associated or underlying disorders

Bilateral cranial temporal arachnoid cysts are associated with a higher incidence of glutaric aciduria type 1. As noted earlier, spinal extradural arachnoid cysts can be associated with lymphedema-distichiasis syndrome and FOXC2 mutations.

Diagnostic workup

These cysts are usually noted on CT or MRI evaluations but may also be noted on prenatal ultrasonography. The gold standard for diagnostics is conventional T1- and T2-weighted FLAIR MRI combined with diffusion-weighted MRI (12). On MRI, arachnoid cysts have well-demarcated, smooth walls and content consistent with CSF signal in all sequences. On magnetic resonance imaging (MRI), the arachnoid cysts have the same signal intensity as CSF on T1 (dark signal), T2 (high signal), T2-FLAIR (dark signal), and diffusion (dark signal). On the apparent diffusion coefficient (ADC) maps, the cyst has a similar high apparent diffusion coefficient value as CSF.

The presence of contrast enhancement, a nodular component, complex wall, heterogeneous FLAIR signal within the cyst, or diffusion restriction is highly indicative of alternative diagnoses. Prior to the wide availability of these techniques, cisternography with water-soluble intrathecal contrast was used to help identify the well-defined borders of an arachnoid cyst from the irregular surface of an epidermoid. This technique is now rarely used and mainly restricted to preoperative evaluations.

Suprasellar arachnoid cysts are often seen on axial neuroimaging studies as rounded areas with imaging characteristics of cerebrospinal fluid located just behind the frontal horns of the lateral ventricles. The three structures resemble the head of a rabbit or "Mickey Mouse," depending on the degree of hydrocephalus. Suprasellar arachnoid cysts cause vertical displacement of the optic chiasm or tracts, upward deflection of the rostral mesencephalon and mammillary bodies, and effacement of the ventral pons (73). Cine-balanced steady-state free precession MRI (bSSFP) can correctly demonstrate communication between arachnoid cysts and the subarachnoid space in 92% compared with operative findings (35). In cases of parasellar arachnoid cysts, preoperative evaluation should include assessment of the hypothalamic-pituitary axis. There may be deficiencies in growth hormone and thyrotropin or stimulation of the hypothalamic-pituitary axis with giantism and obesity (01).

Middle cranial fossa cysts have been categorized based on cyst size (18). Galassi type 1 cysts, which are limited to the anterior part of the temporal fossa and do not cause appreciable mass effect, account for 20% of middle fossa arachnoid cysts. Approximately 50% of middle fossa arachnoid cysts are type 2 cysts, where the cyst occupies the anterior and middle temporal fossa and there may be moderate mass effect. The remaining 30% are type 3 cysts, wherein the cyst occupies the temporal fossa almost completely, the temporal pole is severely atrophic, with compression of the frontal and parietal lobes and striking mass effect.

Bilateral temporal arachnoid cysts may occur in association with glutaric aciduria type 1 in up to 25% of cases. These are usually male infants presenting with signs of encephalopathy; however, less severe symptomatic presentations of the disorder may be seen. Thus, urine should be checked for glutaric acid in cases of bitemporal arachnoid cysts because even simple operations may be risky (36). Neuropsychological testing can occasionally reveal cognitive deficits, and these can correspond to the temporal hypometabolism and blood flow on PET (61; 80). The PET scan abnormalities recover postoperatively, and, in some cases, rather vague preoperative symptoms can improve (61). Intrathecal gadolinium-enhanced MR may also assist in the selection of cases of intracranial arachnoid cyst for surgery (67).

Intraspinal arachnoid cysts are usually readily identified by MRI (53).

Management

Because the natural history of a majority of arachnoid cysts is uneventful, a conservative approach for management can often be used. Asymptomatic cysts have a low rate of cyst enlargement on follow-up imaging, which supports not routinely imaging these patients. When a watch-and-wait policy was adopted in 111 children under the age of 18 years, the size of arachnoid cyst remained stable in 87 (78%), increased in 11 (10%), and decreased in 13 (12%). Patients with symptomatic cysts are significantly younger and more likely to have associated hydrocephalus. An increase in size and the need for surgical intervention was observed more often in young children, and no patient older than four years of age at the time of initial diagnosis became symptomatic or had an increase in cyst size (03).

A decision to intervene surgically depends on the presence or absence of hydrocephalus. Although imaging characteristics of hydrocephalus can be used for guidance, patients may be symptomatic without signs of mass effect from the arachnoid cyst. In such instances, parenchymal fiberoptic transducers could be used with a relatively low complication risk for prolonged intracranial pressure monitoring to aid the decision whether to intervene, even in asymptomatic patients (69). A trial of acetazolamide, which reduces CSF production, could also be used to find which patients may benefit from surgical decompression. One study demonstrated encouraging results, with 94% of patients who responded to the acetazolamide challenge benefiting from surgery (30).

In the presence of hydrocephalus and elevated intracranial pressure, a ventriculo-cysto-peritoneal shunt is preferred (51; 45). In contrast, in the absence of hydrocephalus, the preferred operation is to fenestrate the cyst, producing connections between the cyst and the ventricle, or basal cisterns (17; 29). Endoscopic techniques to fenestrate arachnoid cysts with or without stereotactic guidance are increasingly being used (58; 28; 63; 15; 19; 59).

Cyst aspiration produces early improvement, but recollection almost always occurs. Recurrence is more common when the arachnoid cyst is complex or is associated with multi-compartmental hydrocephalus. With recurrent sellar and suprasellar arachnoid cysts, stereotactic radiosurgery has been used, but the long-term effects are still to be proven (70). In cases with extra-axial hematoma without any symptoms associated with the cyst itself, it may be sufficient to surgically address the hematoma without resecting the arachnoid cyst (79).

An analysis of pooled data comparing four different neurosurgical techniques (open craniotomy for cyst excision, open craniotomy for cyst fenestration, endoscopic fenestration, or cystoperitoneal shunting) found similar success rates in general, but with individual differences, and supported a personalized treatment strategy for cases requiring surgery (04).

In most cases of ventriculo-cysto-peritoneal shunt, hydrocephalus and endocrine symptoms will resolve, but shunt failure with frequent shunt revisions is common (72). A follow-up study of 110 children with intracranial arachnoid cysts treated surgically demonstrated clinical improvement in 87% of patients and radiological improvement in 93% after endoscopic surgery, even higher frequencies of improvement after open microsurgery, and 89% after shunt operations (34).

Spinal subarachnoid cysts can often be surgically excised. Data from a small series of patients undergoing surgical management for extradural spinal arachnoid cysts suggest that symptoms such as lower limb weakness and pain improve in most patients undergoing cyst excision and closure of any dural defect (20).

Special considerations

Pregnancy

There is no evidence that pregnancy influences the growth potential of arachnoid cysts.

Anesthesia

The precautions related to anesthesia are the same as those for any intracranial surgery.

Neurologic clearance

Unless there is evidence of mass effect, patients with arachnoid cysts do not require neurologic clearance to undergo other, unrelated invasive procedures.

Pediatric age group

Some researchers have postulated that individuals with arachnoid cysts may have a higher rate of structural brain injury after trauma, especially if the cysts measure 5 cm or larger (13). However, a systematic review of published case reports for individuals with arachnoid cysts who suffered a structural brain injury during a sport or recreational activity did not find consistent evidence to support recommending against participation in sports for patients with arachnoid cysts (81). As such, patients with arachnoid cysts have no contraindication against their participation in sports, although parents and children should be counseled appropriately regarding the possibility of brain injury following trauma.