Introduction

Choroid plexus cysts (CPCs) are a frequent incidental neuroimaging finding and completely asymptomatic in the vast majority of cases [1]. However, symptomatic CPCs could cause severe disability in either infants [2] or adults [3, 4]. Some researchers describe difficulties with the diagnosis of CPCs when applying standard protocols for CT and MRI [5]. Given the vast spectrum of applicable surgical interventions (from cystoperitoneal shunting or stereotactic aspiration to complete microsurgical excision), optimal treatment modalities are also a matter of debate [6]. Taking into account the rarity of symptomatic CPCs and the abovementioned difficulties with their proper diagnosis and treatment, we decided to perform a systematic review based on case reports and case series [7, 8] in order to determine epidemiological features, localization, symptoms, persistence of concomitant obstructive hydrocephalus, and treatment modalities for symptomatic CPCs.

Materials and methods

Literature search

The literature review was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist [9] with the aim of identifying epidemiological features, variants of localization of the cysts, their symptoms, persistence of concomitant obstructive hydrocephalus, and treatment modalities.

Search strategy

PubMed, Scopus, and Web of Knowledge were searched for available online English-language studies published by April 2023 reporting cases of symptomatic choroid plexus cysts by MeSH terms “choroid plexus”, “cyst”, and “symptomatic”. Reference lists of included studies were consulted as an additional source for literature. No restrictions were included at this stage.

Study selection and inclusion criteria

Abstracts of all identified studies were thoroughly assessed by two independent researchers (A.S. and G.G.), papers that met eligibility criteria were retained, and duplicates were removed. Then the full texts of selected papers were reviewed by authors to apply inclusion criteria. Only published articles with full text or an abstract (containing information of interest) available online in English were included. Data from book chapters and conference abstracts were not included. Exclusion criteria included reviews, letters, and studies not reporting sufficient data. In addition, cases of small asymptomatic CPCs or intraparenchymal cysts due to ectopic choroid plexus [10,11,12] were not included.

Qualitative assessment

Considering that we performed the review based on case reports and case series, we possessed all case series and case reports containing sufficient data and published in journals indexed in internationally recognized databases as being of “good” quality. Case reports missing one investigated parameter were considered “fair”, and those with missing two or more parameters and data extracted from abstracts were considered “poor”.

Data collection

The following data were extracted by two authors (A.S. and M.K.) and critically reviewed by two authors (A.S. and D.S.): number of cases per paper, age and sex of participants, localization of CPCs, clinical presentation on admission, persistence of concomitant obstructive hydrocephalus, treatment method, histological verification, outcome, and follow-up. The presence of obstructive hydrocephalus was assessed by announcement through the text or by reviewing the attached CT and MRI images.

The strategy of literature search is presented in Fig. 1.

Fig. 1
figure 1

PRISMA-based flow diagram of the systematic review

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Results

Search results

Initial searches revealed 301 articles. After excluding 184 duplicates, the titles and abstracts of the remaining 117 papers were screened. A total of 64 Articles were found to be ineligible, and 53 studies met the eligibility criteria. Full text was available for 45 studies. Three valuable abstracts were also presented. Data collected from the literature about published cases of symptomatic CPCs are summarized in Table 1.

Table 1 Summary of the reviewed articles
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Quality assessment

The quality assessment rated 44 studies as “good”, one as “fair”, and three as “poor”.

Demographics, clinics, and surgical data

Overall, 65 cases of symptomatic CPCs were reviewed. The age ranged from newborn to 79 years old: 1 year old and younger—15 (23%); from 1 to 18 years old—18 (28%); and older than 18 years—32 (49%). Among them, 42 (64.6%) were male.

In 27 cases, CPCs were located in the left lateral ventricles, in 22 cases, they were located in the right. The most common localizations among CPCs of the lateral ventricles were trigone (26 cases, 40%) and the body of the lateral ventricle (14 cases, 21.5%). CPCs were located in the frontal and temporal horns of the lateral ventricles in 7 and 1 cases, respectively. Localization in the third ventricle was observed in 14 cases. Two cases of CPCs of the fourth ventricle were also described.

CPCs were the cause of obstructive hydrocephalus in 34 cases. It seems to be associated with the localization of CPCs. Thus, all 7 CPCs located in the frontal horns and 12/14 CPCs in the third ventricle caused CSF pathway obstruction, while only 14/40 (35%) of CPCs in the trigone or body of the lateral ventricle were associated with hydrocephalus.

The most common symptoms of CPCs were signs of increased ICP: headaches and vomiting (32 and 18 cases, respectively). Drowsiness was observed in 4 cases and loss of consciousness in 9 cases. In five cases, CPCs caused seizures. The most common symptom of CPCs in children was increased head circumference, which was noted in 10 cases. Among patients older than 50 years old, gait disturbance was a common symptom (4/10). Short-term memory loss or episodes of global amnesia were presented in 4 cases. Hemiparesis or monoparesis was noted in four cases. Other signs and symptoms such as hallucinations (1), blurred vision (1), myoclonic jerks of the extremities (1), disconjugate or restricted gaze (1), and CN VI palsy (1) were considered non-specific.

The main treatment approaches for symptomatic CPCs were microsurgical excision (24, 37%), microsurgical fenestration (11, 17%), endoscopic fenestration (13, 20%), and total endoscopic excision (7, 11%). In three cases, ventriculoperitoneal or cystoperitoneal shunting was performed as a first-line procedure. In most cases, microsurgical excision was curative, while in one case, it was supplemented by ventriculoperitoneal shunting. Microsurgical fenestration tends to be more often supplemented by cysto-ventriculoperitoneal shunting, which was performed in 4/10 cases. In one case, microsurgical fenestration was unsuccessful, and further microsurgical excision of the cyst was to be performed. On the contrary, there were no cases of endoscopic excision or fenestration that demanded conversion to microsurgical procedures. In one case, endoscopic fenestration was supplemented by cysto-ventriculoperitoneal shunting. Two cases of cystoperitoneal shunting performed initially as a curative procedure demanded further microsurgical excision of the CPCs. One case of stereotactic puncture of the CPC was described. In 10 cases, observation was chosen with no mention of further treatment.

In 44 (80%) cases, patients improved after surgery. There was no evidence of serious complications. In two cases, patients had persistent headaches, in one—memory impairment and hemianopsia, and in one other case—transient hemiparesis. One patient died from other pathology unrelated to the treatment and surgery. In one case, endoscopic excision of the cyst’s wall was followed by intraventricular hemorrhage [40], which resolved within a hospital stay. No recurrent CPCs were observed. The mean follow-up was 10 months, ranging from assessment during in-hospital period to 10 years.

Illustrative case

A previously healthy 32-year-old male was presented to our neurosurgical department with a 2-month history of postural headaches (from 4 to 6 points on the visual analog scale on admission) and dizziness. He had no history of trauma or illness. The general physical and neurological examination on admission was unremarkable, with the exception of a slight unsteadiness during the Romberg test without lateralization. MRI scans revealed a large cystic lesion in the trigone of the left lateral ventricle with signs of an isolated occipital horn (Fig. 2A). Other parts of the lateral ventricles, the third and fourth ventricles, were not dilated. Fundoscopy revealed no signs of papilledema. A lumbar puncture was performed. The CSF opening pressure was 20 cm H2O.

Fig. 2
figure 2

A Axial T2 MRI showing choroid a plexus cyst in the trigone of the left lateral ventricle. Note the small daughter cyst laterally. B Postoperative axial T2 MRI

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Endoscopic fenestration of the CPC through the standard occipital access route was performed, and the cyst was communicated with the left lateral ventricle (Fig. 3).

Fig. 3
figure 3

A The large CPC seen immediately after the introduction of the endoscope into the occipital horn of the left lateral ventricle. B After the coagulation of the cyst wall, the choroid plexus was observed. C Smaller daughter cyst. D Fenestration of the cyst wall was performed after additional coagulation

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An endoscopic septostomy was also performed. Control CT scans revealed a remarkable decrease in the cyst’s volume (Fig. 2B). The postoperative course was uneventful, and symptoms resolved. The patient was discharged on postoperative day 3 and was symptom-free on one-month follow-up.

Discussion

CPCs are usually detected prenatally, with an incidence of 1.2% in fetuses [50]. However, cases of de-novo formation of CPCs in adults, presumably after VP-shunting, are also described [51]. The vast majority of CPCs are asymptomatic and are incidental findings during neuroimaging studies or autopsies.

Instead of incidentally discovered CPCs, symptomatic ones are rare. Walter Dandy stated: “I know of no instance when a cyst of the choroid plexus has caused symptoms…” [52]. The first symptomatic case of supposed CPC was described in 1876 by Brown [53]. Although the lesion was distinctly described as a thin-walled cyst arising from the choroid plexus and filled with clear serous fluid, no histopathological description was provided. For this reason, some authors [15] refuse to recognize the described case as the first evidence of a symptomatic choroid plexus cyst. The first histologically verified case of symptomatic CPC was presented by Baker and Gottlieb in 1956 [13]. The cyst was removed by microsurgery with complete resolution of symptoms. Since then, the vast majority of publications on the symptomatic CPCs are case reports with rare small case series.

Classification and probable pathogenesis

By their nature, choroid plexus cysts are intraventricular, non-colloid neuroepithelial cysts [29]. According to Czervionke et al., CPCs are the most common intraventricular neuroepithelial cysts (Fig. 4).

Fig. 4
figure 4

Classification of the neuroepithelial cysts by Czervionke et al. [3]

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Yeates et al. postulated [4] that intraventricular arachnoid cysts originate from the ependymal layer of the tela choroidea covering the vascular mesenchyma, which later projects into the lateral ventricle through the choroid fissure as the choroid plexus. The blood vessels traverse the thin tela choroidea, which consists of an invagination of pia mater enclosing the arachnoid stroma, on their way to the choroid plexus [11].

Martinez-Lage et al. consider CPCs intraventricular arachnoid cysts and propose their origin to be secondary to the displacement of arachnoid cells by the vascular mesenchyma, through the choroid fissure, during the process of choroid plexus development [11].

According to Parizek et al. [37], the accumulation of cerebrospinal fluid secreted by the choroid plexus is responsible for the increase in the cyst volume.

Contrary to ependymal cysts, the walls of CPCs could easily be peeled off the ventricular ependyma but were firmly attached to the choroid plexus, usually at the point of the temporal choroidal fissure [1, 23]. In one case described by Martinez-Lage et al., the cyst’s wall was firmly adhered to the ventricular wall, although histological examination confirmed an arachnoid cyst [11].

Histologically, CPCs are characterized by the presence of cuboid choroid plexus cells. This type of cell was found in specimens and described in 47 reports included in this review.

Symptoms

The choroid plexus is a mobile structure; thus, if firmly attached to the plexus, CPCs could migrate within the lateral ventricle and even protrude to the third ventricle, causing dynamic occlusion of the foramen of Monro. This mechanism is more common for CPCs located within the frontal horn of the lateral ventricle or in the third ventricle [34, 37, 39, 48]. Although a few authors described patients suffering from postural headaches who had had CPCs in trigone [4; 35], Baalen et al. described the protrusion of a choroid plexus cyst from the third ventricle to the lateral ventricle through the foramen of Monro while an infant was crying [41].

Numaguchi et al. presented two cases of big CPCs of the lateral ventricles that somehow were asymptomatic [29]. In two additional cases, although not clinically manifested, occlusive hydrocephalus was obvious [Czrevionke, 1987; Becker, 2002]. Baka et al. described a relatively small CPS that manifested as mild confusion and loss of balance after hemorrhage inside the cyst [35].

Diagnosis

Before the widespread introduction of CT and MRI techniques, the most common method for visualization of CPCs was pneumoventriculography. This approach—to see isolated cysts within the ventricle by contrasting the outside ventricular cave—is still up-to-date. Routine CT and MRI are unable to detect the cyst’s wall, misdiagnosing actual CPC as monoventricular hydrocephalus [5]. The application of positive ventriculography by lumbar injection of contrast substantially increases the diagnostic value of CT in cases of CPCs. Usually, 1,5T MRI with multiplanar CISS, FIESTA, or DRIVE protocols could clearly show cyst walls, evaluate ventricular anatomy, and plan surgical intervention [2, 42, 45].

Treatment options

Complete microsurgical excision of the cyst’s walls was the main surgical strategy until 1986, when Nakasu et al. showed comparable effects of fenestration of the cyst [25]. Depending on the localization of the cyst within the ventricular system, transcallosal and transcortical (through the middle temporal gyrus) approaches were most applicable. In some cases, microsurgical excision was the final treatment option after an unsuccessful shunting [20, 31]. On the other hand, total excision had never required adjuvant treatment, with the exception of one case of additional cysto-ventriculoperitoneal shunting [32].

The first use of a ventriculoscope for cyst wall fenestration and cysto-ventriculoperitoneal shunt placement was reported by Martinez-Lage et al. in 1992 [11]. Although the current development of minimally invasive techniques has made microsurgical procedures to a large extent safe and effective, the tendency has been noted to shift from microsurgical to endoscopic procedures over the past two decades (Fig. 5).

Fig. 5
figure 5

Trends in surgical treatment of CPS

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Despite one case of minor intraventricular hemorrhage after endoscopic excision of the cyst walls, no serious complications were reported, neither after microsurgical nor endoscopic procedures. There is no data available confirming the advantage of total excision of the cyst walls on fenestration, either microsurgically or endoscopically.

Obviously, every surgeon prefers to choose treatment options from his personal field of expertise, but in the case of equally available microsurgical and endoscopic approaches (which are necessarily in high-volume neurosurgical departments), the last one seems to be preferable in cases of symptomatic CPCs.

Cystoperitoneal or cysto-ventriculoperitoneal shunting is more likely to be an adjuvant procedure than a curative one for patients with CPCs. This statement is supported by the fact that only one successful VP-shunting case of CPC has been described in the literature. Stereotactic puncture and aspiration of the cyst’s contents, as described by Pelletier et al. [33], are not widespread treatment options for CPCs.

Some previously symptomatic CPCs could resolve spontaneously [Lin, 2021], so observation could also be a valuable option in selected cases.

Proposed diagnostic algorithm and treatment strategy for CPC

Based on the reviewed literature, we recommend supplementing routine MRI studies with CISS, FIESTA, or the DRIVE protocol in all patients with suspected CPC or monoventricular hydrocephalus. Positive CT-ventriculography may be considered as an alternative or adjunct to the MRI. Symptomatic cases of CPC with obvious signs of cerebral compression or obstructive hydrocephalus should be considered as candidates for surgical treatment. We suggest endoscopic fenestration of the cyst’s walls as the first-line option that could be converted to microsurgical fenestration if required. A complete excision of the cyst walls is not necessary. Considering the possibility of life-long complications, shunting procedures should be avoided. Observation as a treatment strategy can be used in carefully selected cases due to contraindications for surgery.

Conclusion

The rarity of symptomatic cases of CPCs makes an evidence-based approach to diagnosis and treatment difficult. The collection of new well-described series in the future will allow for the discovery of optimal management algorithms through performing meta-analyses. Nevertheless, we hope that our systematic review will help to solve some difficulties in decision-making for specialists who are to treat the patient with CPC for the first time or to perform proper high-volume research. Based on the current literature and personal experience, we are advised to use endoscopic procedures as the primary approach for symptomatic cases of CPCs because they are most effective and complication-free.