Intracranial cysts: incidental or neurodevelopmental?

Intracranial cysts are fluid-filled sacs within the brain. There is a diversity of intracranial cysts with different incidences in addition to the growing awareness about comorbidities and the consequences. The present study aimed to evaluate cystic findings in children who were admitted to the department of pediatric neurology. Children who were admitted to the Clinic of Pediatric Neurology and who had an MRI between 2016 and 2021 were evaluated. The MRI examination was performed with the pediatric epilepsy protocol. Children with primary intracranial cysts were enrolled in the study. Demographic and clinical findings were evaluated from the hospital’s database and patients’ files. Among the 78 patients, 36 (46.2%) were male and 42 (53.8%) were female. The mean age was 7 ± 5.4 years. The most frequent presenting complaint was a seizure (47.4%). Approximately one-quarter (28.2%) had mental and/or motor retardation. Nine (11.5%) of the children had a neuropsychiatric diagnosis. Most of the cysts were located at the midline (41%) with the majority located extra-axial (71.8%) and supratentorial (78.2%). Arachnoid cysts were observed most frequently with a percentage of 64.1%, followed by pineal cysts (15.4%). The history of seizure, epilepsy, presence of mental retardation, and neuropsychiatric problems were evaluated according to the population ratios based on z approximation in which significantly higher rates were observed among cases with intracranial cysts. Intracranial cysts should be taken into consideration for comorbid pathologies, especially in the childhood period. Early evaluation in patients with intracranial cysts for developmental delay and neuropsychiatric problems is important.


Introduction
Intracranial cysts are fluid-filled sacs within the brain that can be formed prenatally or postnatally. Cysts are commonly seen on magnetic resonance imaging (MRI) and computed tomography (CT) imaging studies. The spectrum of histopathology of intracranial cysts is broad [1]. According to etiologic factors, they can be classified as normal variants, developmental cystic lesions, cysts secondary to perinatal injury, vascular cyst-like structures, hemorrhagic cysts, and infectious cysts [2]. However, there is a diversity of intracranial cysts with different incidences.
Among commonly seen cysts, arachnoid cysts have a prevalence of approximately 2% on imaging [3][4][5]. They tend to occur more frequently in boys when compared to girls and the prevalence does not change with age [5][6][7][8]. They are mostly located in the anterior, middle fossa, or retrocerebellar location [3,[6][7][8][9]. They are mostly detected incidentally with varying sizes [5,6,10]. Although the majority do not require treatment, they must be treated in rare in cases.
Pineal cysts are also frequently seen in children on MRI with an increasing prevalence with age up to young adulthood and decreasing prevalence with advancing age in adulthood [11,12]. They are more frequently seen in girls [11][12][13][14]. They are almost always asymptomatic, although the risk of symptoms rises as the size of the increases, especially for cysts larger than 1 cm [5,15].
Porencephalic cysts consist of an area of encephalomalacia formed in the 3rd trimester or postnatally as a result of destructive processes like hemorrhage, surgery, or infection. The prevalence of porencephalic cysts is 2.5% [16][17][18].
Neuroglial cysts (glioependymal cysts) are congenital lesions that develop as a result of the sequestration of neural tube embryonic elements that develop into a fluid-filled cavity lined by glial cells. They are located within the white matter [19].
Subependymal cysts can be congenital or acquired. Those that are congenital can be found in association with congenital viral infections, metabolic disorders, chromosomal disorders, and maternal cocaine usage. However, they can also be found isolated in healthy newborns [16,20,21].
Choroidal fissure cysts are almost always incidental findings with localization on the mesial surface of the temporal lobe in between the hippocampus and the diencephalon. Generally, they are static lesions [5,22,23].
There is also a growing awareness about comorbidities and the consequences of cysts. It has been shown that some are caused by a pathological process during developmental stages [24].
Among intracranial cysts, the incidence of arachnoid cysts rises in cases with Down syndrome, schizencephaly, mucopolysaccharidosis, and neurofibromatosis [29], demonstrating an increased prevalence with underlying abnormalities of the brain.
Recent publications have demonstrated benefits in various symptoms like seizures, headache, and cognition after surgery [29,30].
The present study aimed to evaluate cystic findings in children who were admitted to the department of pediatric neurology regardless of the symptomatology. The type, localization, and accompanying clinical findings were documented.

Material and methods
Study performed in Near East University and Dr Suat Gunsel University in North Cyprus. Children who were admitted to the Department of Pedatric Neurology who had an MRI between 2016 and 2021 evaluated.
The MRI examinations were performed using 1.5 Tesla (Siemens) and 3 Tesla (Siemens) unit scanners with a pediatric epilepsy protocol. The protocol includes (a) sagittal T1-weighted spin-eco, (b) axial T2-weighted fast spin-echo, (c) coronal oblique fast multiplanar inversion recovery, (d) coronal oblique fast fluid-attenuated inversion recovery, (e) axial diffusion (one-shot, spin-echo echoplanar), b = 1000 to all directions, and (f) axial three-dimensional spoiled gradient. A total of 78 patients underwent an MRI scan. MRI scans were administered without the use of contrast material as a routine procedure. If suspicious findings were observed during the scan, gadolinium was used for further detailed study.
The MRI scans were evaluated by the same radiologist. Those that were diagnosed as primary intracranial cysts were enrolled in the study. Demographic and clinical findings were evaluated from the hospital's database and patients' files.
Statistical Package for Social Sciences (version 17.0; IBM, Armonk, NY) was used for statistical analysis. The chi-square test, Fisher's exact test, and descriptive statistics were used. A P-value of less than 0.05 was accepted as being statistically significant. The binomial test was used for the comparison of incidence based on population frequency.

Results
Among 78 patients, 36 (46.2%) were male and 42 (53.8%) were female. The mean age was 7 ± 54 years. The most frequent presenting complaint was a seizure (47.4%). Approximately one-quarter of the patients had mental and/or motor retardation. Nine (11.5%) of them had a neuropsychiatric diagnosis. The clinical findings of the patients are summarized in Table 1.
MRI evaluations revealed that most of the cysts were located at the midline (41%), where the majority were located extra-axial (71.8%) and supratentorial (78.2%).
Among the cysts, the most frequently seen type was arachnoid cysts with a percentage of 64.1 (50 cases). The second leading type was pineal cysts, which were found in 12 cases (15.4%). The rest were porencephalic cysts, neuroglial cysts, and others (subependymal cyst and choroidal fissure cyst) with percentages of 10.3 (8 cases), 7.7 (6 cases), and 2.6 (2 cases), respectively.
The majority of the cysts were ≥ 10 mm. They were mostly located at the midline (41%). Among the lobes of the brain, they were mostly located within the temporal lobe (29.5%). Findings on MRI are summarized in Table 2.
Findings according to the localization of the cysts are given in Table 3. Intra-axial and supratentorial cysts were demonstrated to be significantly related to seizures and epilepsy. Also, females had statistically significantly more midline cysts when compared to males.
Among the 78 patients, one of them with an arachnoid cyst required an emergent neurosurgical procedure due to increased intracranial pressure presented with seizure and papilledema.
The history of seizure, epilepsy, presence of mental retardation, and neuropsychiatric problems were evaluated according to the population ratios based on z approximation. There were statistically significantly higher rates within the population with intracranial cysts, as shown in Table 4.

Discussion
The present study demonstrated a slightly female predominance without any statistical significance. It was demonstrated that the prevalence arachnoid cyst was higher in male, whereas pineal cysts were more prevalent in females [5].
The main presenting complaint of patients was a seizure (47.4%) and headache (21.8%). Arachnoid cysts can be the focus of epileptic seizures [25]. An increased seizure frequency had been described in the case of temporal cysts [30,31]. Additionally, epileptic discharges may not correlate with the location of the cyst in the case of epilepsy [32]. The most common symptom of a middle cranial fossa AC is headache [32]. Furthermore, contralateral motor weakness, seizures, and proptosis have been described [33][34][35]. Within our group of patients, mental retardation was documented at a rate of 25.6%. In another study, up to 31% mental impairment was described in 10% of cases and an increased incidence of developmental delay was observed [32]. Altogether, it can be postulated that cysts might be a result of a maldevelopmental process.
Intracranial cysts were mostly located at the midline (41%), followed by the temporal lobe (29.5), and the majority was ≥ 10 mm.
Most of them were extra-axial (71.8%) and supratentorial (78.2%) when localization was evaluated according to axial structures and tentorium. Intra-axial and supratentorial lesions were found to be highly related to seizure and epilepsy as expected. Although temporal cysts were shown to be more related to seizures [30,31], no statistically significant correlation was found within that group of patients. This  Midline cysts were demonstrated to be statistically higher (P: 0.046) in females. This may be due to the number of pineal cysts, as they were the second leading type of intracranial cysts within the group.
Arachnoid cysts were the leading type of cyst, followed by pineal cysts.
In addition to the initial diagnosis, there was a high rate of comorbidities within the group. The percentages of mental retardation, motor retardation, and neuropsychiatric status were 25.6, 28.2, and 11.5, respectively.
When compared to the prevalence in the normal population, the rates of seizure, epilepsy, mental retardation, and the presence of neuropsychiatric status were found to be significantly higher in the study group. This may indicate a maldevelopmental process for this group of patients.
Likewise, neuropsychiatric problems like ADHD, ophthalmological problems, sensorineural hearing loss, and narcolepsy have also been described in cases with intracranial cysts [36].
This may indicate a developmental aberration in patients with intracranial cysts, supporting the evidence demonstrating an increased prevalence of cysts with underlying abnormalities of the brain like in cases with Down syndrome, schizencephaly mucopolysaccharidosis, and neurofibromatosis [29].
In 1 of the 78 patients, an emergent neurosurgery procedure was performed due to increased intracranial pressure presenting with seizure and papilledema. With increasing awareness, surgical attempts have also been made for these groups of patients. In a prospective study including pediatric cases with temporal AC, improvement of cognitive functions after micro-neurosurgical fenestration was documented [30]. In another study involving pediatric group of patients with a mean age of 9.4 years with temporal, frontal, and frontotemporal cysts, no improvement in intellectual abilities after surgery was observed. On the other hand, within the same study, there was an improvement in FSQ, verbal comprehension tests indicating the possible greater recovery rate in the developing brain [37].
The present study involved patients presenting to the clinic of pediatric neurology with complaints. Records about asymptomatic cases and long-term follow-up of cases with intracranial cysts were not documented, which is one of the main limitations of the study.

Conclusion
The prevalence of seizure, epilepsy, mental retardation, and the presence of neuropsychiatric status were higher in patients with intracranial cysts. There needs to be greater awareness of increased comorbidities in children with intracranial cysts, particularly for the early evaluation and management of developmental delay and neuropsychiatric problems in addition to the need for neurosurgical procedures. Further studies enrolling a higher number of patients including cases with incidentally detected intracranial cysts and long-term follow-up results are required in this field.
Acknowledgements We thank to Prof Dr Eray Dirik who mentored us.