Endoscopic third ventriculostomy (ETV) or ventriculoperitoneal shunt (VPS) for paediatric hydrocephalus due to primary aqueductal stenosis.

PURPOSE: The purpose of this study was to compare outcomes of endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) in children with symptomatic triventricular hydrocephalus due to primary aqueductal stenosis. METHOD: This is a retrospective analytical study. Patients who underwent either ETV or VPS as the first procedure for hydrocephalus due to primary aqueductal stenosis were included in the study. RESULT: A total of 89 children were included in the study for analysis. The mean age was 8.4 years. Forty-four (49.4%) had their first surgery as ETV and 45 (50.6%) had their first surgery as VPS. Overall, 34 (38.2%) patients required a second surgery (either ETV or VPS) for persistent or recurrent hydrocephalus. The mean follow-up duration was 832.9 days. The overall complication rate was 13.5%. The mean timing of the second surgery after index surgery was 601.35 days. Factors associated with a second surgery were the presence of complications, high protein in cerebrospinal fluid, the relative change of frontal-occipital horn ratio (FOHR) and Evans' index. The survival of the first surgery was superior in ETV (751.55 days) compared to VPS (454.49 days), p = 0.013. The relative change of fronto-occipital horn index ratio (FOIR) was high in the VPS (mean 7.28%) group compared to the ETV (mean 4.40%), p = 0.001 group. CONCLUSION: Overall procedural survival was better after ETV than VPS for hydrocephalus due to aqueductal stenosis. VPS causes more reduction in linear indices of ventricles as compared to ETV, however, is not associated with the success or complication of the procedure.

A novel SMARCC1 BAFopathy implicates neural progenitor epigenetic dysregulation in human hydrocephalus.

Hydrocephalus, characterized by cerebral ventriculomegaly, is the most common disorder requiring brain surgery in children. Recent studies have implicated SMARCC1, a component of the BRG1-associated factor (BAF) chromatin remodelling complex, as a candidate congenital hydrocephalus gene. However, SMARCC1 variants have not been systematically examined in a large patient cohort or conclusively linked with a human syndrome. Moreover, congenital hydrocephalus-associated SMARCC1 variants have not been functionally validated or mechanistically studied in vivo. Here, we aimed to assess the prevalence of SMARCC1 variants in an expanded patient cohort, describe associated clinical and radiographic phenotypes, and assess the impact of Smarcc1 depletion in a novel Xenopus tropicalis model of congenital hydrocephalus. To do this, we performed a genetic association study using whole-exome sequencing from a cohort consisting of 2697 total ventriculomegalic trios, including patients with neurosurgically-treated congenital hydrocephalus, that total 8091 exomes collected over 7 years (2016-23). A comparison control cohort consisted of 1798 exomes from unaffected siblings of patients with autism spectrum disorder and their unaffected parents were sourced from the Simons Simplex Collection. Enrichment and impact on protein structure were assessed in identified variants. Effects on the human fetal brain transcriptome were examined with RNA-sequencing and Smarcc1 knockdowns were generated in Xenopus and studied using optical coherence tomography imaging, in situ hybridization and immunofluorescence. SMARCC1 surpassed genome-wide significance thresholds, yielding six rare, protein-altering de novo variants localized to highly conserved residues in key functional domains. Patients exhibited hydrocephalus with aqueductal stenosis; corpus callosum abnormalities, developmental delay, and cardiac defects were also common. Xenopus knockdowns recapitulated both aqueductal stenosis and cardiac defects and were rescued by wild-type but not patient-specific variant SMARCC1. Hydrocephalic SMARCC1-variant human fetal brain and Smarcc1-variant Xenopus brain exhibited a similarly altered expression of key genes linked to midgestational neurogenesis, including the transcription factors NEUROD2 and MAB21L2. These results suggest de novo variants in SMARCC1 cause a novel human BAFopathy we term 'SMARCC1-associated developmental dysgenesis syndrome', characterized by variable presence of cerebral ventriculomegaly, aqueductal stenosis, developmental delay and a variety of structural brain or cardiac defects. These data underscore the importance of SMARCC1 and the BAF chromatin remodelling complex for human brain morphogenesis and provide evidence for a 'neural stem cell' paradigm of congenital hydrocephalus pathogenesis. These results highlight utility of trio-based whole-exome sequencing for identifying pathogenic variants in sporadic congenital structural brain disorders and suggest whole-exome sequencing may be a valuable adjunct in clinical management of congenital hydrocephalus patients.

Assessment of the prevalence and associated risk factors of pediatric hydrocephalus in diagnostic centers in Addis Ababa, Ethiopia.

BACKGROUND: Hydrocephalus (HCP) is a common disorder of cerebral spinal fluid (CSF) physiology resulting in abnormal expansion of the cerebral ventricles. Infants commonly present with progressive macrocephaly whereas children older than 2 years generally present with signs and symptoms of intracranial hypertension. Neither qualitatively nor quantitatively are there adequate data to determine the prevalence and incidence of HCP in the developing world. HCP is a treatable condition that when left untreated, has fatal consequences. OBJECTIVE: The objective of this study was to assess the prevalence of pediatric HCP and associated risk factors in diagnostic centers in Addis Ababa, Ethiopia. METHODS: This study was conducted using a cross-sectional facility-based study design over a two-time period, i.e. a 2-year retrospective data collection from January 2018 to January 2020 included 1101 patients and a prospective data collection from May 2019 to February 2020 included 99 patients. Children aged 5 years and below who came to the selected diagnostic centers for MRI/CT examination were studied. The collected data were analyzed using binary logistic regression. RESULT: The retrospective study included 639(58%) males and 462 (42%) females. The mean age calculated was 22.3 months. Infants aged younger than 24 months 753 (68.4%) were significantly associated with HCP development (P < 0.05). In the retrospective study, HCP etiologies; Aqueductal stenosis (17.9%), Neural Tube defects (NTDs) (35.7%), post-infectious (10.1%) were identified. In the prospective study, the gender and age distribution was 57(57.6%) males, 42 (42.4%) females, 60.6% infants aged younger than 24 months with a mean age of 24.9 months. Inadequate consumption of folic acid and development of HCP was found to be statistically significant (P < 0.05). In the prospective study, HCP etiologies; Aqueductal stenosis (26.1%), Neural Tube defects (26.08%), and post-infectious (8.69%) were identified. The 3 years prevalence of HCP calculated in both studies was 22% (223 per 1000 live births). CONCLUSION: The results of this study suggest that the high prevalence of HCP was due to the high prevalence of aqueductal stenosis and neural tube defects; with a small contribution of post-infectious causes. The majority of infants who present with HCP were aged younger than 24 months.

Prediction of endoscopic third ventriculostomy (ETV) success with preoperative third ventricle floor bowing (TVFB): a supplement to ETV success score.

Preoperative judgement of which children is likely to benefit from endoscopic third ventriculostomy (ETV) is still the most difficult challenge. This study aimed to compare the efficiency of third ventricular floor bowing (TVFB) and ETV success score (ETVSS) in selecting ETV candidates and achieve a better preoperative patient selection method for ETV based on our institutional experience. Children (≤ 16 years old) with newly diagnosed hydrocephalus treated with ETV between January 2013 and June 2018 were included in this prospective study. Patients with TVFB will receive ETV procedure in the pediatric subgroup of our department. ETVSS was calculated in every patient. The ETVSS predicted ETV success rate and the actual ETV success rate in our institution were compared and further analyzed. One hundred twenty-nine children with TVFB were enrolled in our study. The mean age at ETV was 5.84 ± 5.17 years (range, 0.04-16). Brain tumors, aqueductal stenosis, and inflammatory are the most common hydrocephalus etiologies. The most common complication was noninfectious fever (3.1%). During the average follow-up of 19.5 ± 14.95 months, twenty-five patients had depicted ETV failure. The actual ETV success rate (81%) in our study was higher than the success rate (69%) predicted by ETVSS. TVFB is a pragmatic, efficient, and simple model to predict the ETV outcome. We suggest that for hydrocephalic patients with preoperative third ventricular floor bowing, ETV should be the first-treatment choice regardless of the ETV success score. And for patients without such sign, ETVSS should be applied to select ETV candidates.

Congenital Aqueductal Stenosis: Findings at Fetal MRI That Accurately Predict a Postnatal Diagnosis.

BACKGROUND AND PURPOSE: Congenital aqueductal stenosis is a common cause of prenatal ventriculomegaly. An accurate diagnosis provides prognostic information and may guide obstetric management. The purpose of this study was to identify specific anatomic findings on prenatal MR imaging that can be used as predictors of congenital aqueductal stenosis. MATERIALS AND METHODS: Prenatal and postnatal MRIs of fetuses referred to our institution for ventriculomegaly between June 2008 and August 2015 were reviewed. Imaging findings in postnatally confirmed congenital aqueductal stenosis (disease group) were compared with those of ventriculomegaly cases from other causes (control group). Univariate analysis was performed using the Fisher exact test and the Wilcoxon rank test, and multivariate analysis, via the random forest method. RESULTS: Forty-three cases of ventriculomegaly had a confirmed postnatal diagnosis of congenital aqueductal stenosis. Thirty-two ventriculomegaly cases negative for congenital aqueductal stenosis were included in the control group. Dominant findings associated with an accurate prenatal diagnosis of congenital aqueductal stenosis on multivariate analysis included the following: enlarged inferior third ventricular recesses, enlargement of the lateral ventricles and third ventricle, and an abnormal corpus callosum. Findings that significantly increase the probability of congenital aqueductal stenosis (high positive predictive value) included the following: enlarged third ventricular recesses, aqueduct funneling, hemorrhage in the cerebral aqueduct, ventricular diverticulum, rhombencephalosynapsis, and dystroglycanopathy-related cerebellar dysplasia. CONCLUSIONS: Our study identified specific characteristics on fetal MR imaging that can be used as predictors of the diagnosis of congenital aqueductal stenosis. Most of these findings are secondary to the obstructive nature of the resulting hydrocephalus. Common associated malformations such as rhombencephalosynapsis and dystroglycanopathies should also increase the suspicion of congenital aqueductal stenosis when present with ventriculomegaly.

Telencephalic Flexure and Malformations of the Lateral Cerebral (Sylvian) Fissure.

After sagittal division of the prosencephalon at 4.5 weeks of gestation, the early fetal cerebral hemisphere bends or rotates posteroventrally from seven weeks of gestation. The posterior pole of the telencephalon thus becomes not the occipital but the temporal lobe as the telencephalic flexure forms the operculum and finally the lateral cerebral or Sylvian fissure. The ventral part is infolded to become the insula. The frontal and temporal lips of the Sylvian fissure, as well as the insula, all derive from the ventral margin of the primitive telencephalon, hence may be influenced by genetic mutations with a ventrodorsal gradient of expression. The telencephalic flexure also contributes to a shift of the hippocampus from a dorsal to a ventral position, the early rostral pole of the hippocampus becoming caudal and dorsal becoming ventral. The occipital horn is the most recent recess of the lateral ventricle, hence most vulnerable to anatomic variations that affect the calcarine fissure. Many major malformations include lack of telencephalic flexure (holoprosencephaly, extreme micrencephaly) or dysplastic Sylvian fissure (lissencephalies, hemimegalencephaly, schizencephaly). Although fissures and sulci are genetically programmed, mechanical forces of growth and volume expansion are proposed to be mainly extrinsic (including ventricles) for fissures and intrinsic for sulci. In fetal hydrocephalus, the telencephalic flexure is less affected because ventricular dilatation occurs later in gestation. Flexures can be detected prenatally by ultrasound and fetal magnetic resonance imaging and should be described neuropathologically in cerebral malformations.

Endoscopic third ventriculostomy through lamina terminalis: A feasible alternative to standard endoscopic third ventriculostomy.

CONTEXT: Endoscopic third ventriculostomy (ETV), wherein a stoma is created in the floor of the third ventricle, has now become the standard procedure for noncommunicating hydrocephalus across the world. However, in certain situations, this procedure may pose technical difficulties. These include a narrow prepontine space, vascularized third ventricular floor, the presence of prominent blood vessels traversing within the prepontine space, significant basal exudates, thickened and ill-defined third ventricular floor, and distorted floor anatomy. In such situations, an endoscopic lamina terminalis opening may provide a safer and more effective alternative to the standard technique. AIMS: The paper aims to discuss the different indications, technical nuances, and outcome of endoscopic third ventriculostomy through the lamina terminalis (ETV LT) utilizing the standard transventricular transforaminal route. SETTINGS AND DESIGN: A total of 240 patients underwent ETV between January 2007 and January 2014. Of these patients, 8 patients required an EVT LT and these patients formed the subset of patients for the present study. In all the 8 patients, the decision to perform fenestration of the LT during the endoscopic procedure was taken intraoperatively. We qualified a procedure to be a success when a second procedure was not required subsequently. RESULTS: Of the eight patients in whom ETV LT was done, four had aqueductal stenosis (including one case of post-primary ETV), three patients were diagnosed with post-meningitic hydrocephalus, and the remaining patient had a posterior fossa tumor. The procedure was successful in 6 of our patients who did not require a second procedure till the last follow-up. CONCLUSIONS: Endoscopic transventricular transforaminal LT fenestration with a flexible neuroendoscope is a feasible alternative to the standard ETV when technical difficulties precludes safe performance of the latter procedure.

[Case Report of Cerebellar Vermis Arteriovenous Malformation Presenting with Hydrocephalus due to Aqueductal Stenosis].

A 56-year-old man complained of gait disturbance and confused thinking. Magnetic resonance imaging(MRI)revealed an arteriovenous malformation(AVM)of the cerebellar vermis(Spetzler-Martin grade IV)causing hydrocephalus. One dilated precentral cerebellar vein was compressing the aqueduct. After feeder embolization over 3 sessions using N-butyl cyanoacrylate(NBCA), the nidus was reduced to one-third in size. However, symptoms remained unimproved, and endoscopic third ventriculostomy(ETV)was performed. The third ventricle showed thinning of the floor, with a fenestration in part of the floor. Radiological findings and clinical symptoms improved, and the patient returned home after rehabilitation. The condition of the patient remained stable as of six months later. On angiography, the draining vein showed a pressure of 20 mmHg with no change in the residual AVM. Embolization alone achieved a reduction in nidus volume, but could not reduce venous pressure, and combination therapy including ETV proved necessary. Cases with hydrocephalus due to aqueductal stenosis by AVM are extremely rare. This pathology is discussed with reference to the literature.

Preoperative prognostic value of MRI findings in 108 patients with idiopathic normal pressure hydrocephalus.

BACKGROUND AND PURPOSE: MR imaging is used in the diagnostic evaluation of patients with idiopathic normal pressure hydrocephalus. The aim of this study was to describe the prevalence of several imaging features and their prognostic use in the selection of shunt candidates with idiopathic normal pressure hydrocephalus. MATERIALS AND METHODS: Preoperative MR imaging scans of the brain were retrospectively evaluated in 108 patients with idiopathic normal pressure hydrocephalus who had undergone a standardized, clinical evaluation before and 12 months after shunt surgery. The MR imaging features investigated were the Evans index, callosal angle, narrow sulci at the high convexity, dilation of the Sylvian fissure, diameters of the third ventricle and temporal horns, disproportionately enlarged subarachnoid space hydrocephalus, flow void through the aqueduct, focal bulging of the roof of the lateral ventricles, deep white matter hyperintensities, periventricular hyperintensities, and focal widening of sulci and aqueductal stenosis. RESULTS: In logistic regression models, with shunt outcome as a dependent variable, the ORs for the independent variables, callosal angle, disproportionately enlarged subarachnoid space hydrocephalus, and temporal horns, were significant (P < .05), both in univariate analyses and when adjusted for age, sex, and previous stroke. CONCLUSIONS: A small callosal angle, wide temporal horns, and occurrence of disproportionately enlarged subarachnoid space hydrocephalus are common in patients with idiopathic normal pressure hydrocephalus and were significant predictors of a positive shunt outcome. These noninvasive and easily assessed radiologic markers could aid in the selection of candidates for shunt surgery.

Third ventriculostomy and fourth ventricle outlets obstruction.

A dilated fourth ventricle due to outlet obstruction is a clinical-radiologic entity with symptoms similar to those of a posterior fossa space-occupying lesion. Indeed, blockage of the foramina of Luschka and Magendie and of the aqueduct results in a "trapped" fourth ventricle. Continued cerebrospinal fluid (CSF) production within the fourth ventricle leads to cystic dilatation of the fourth ventricle. We could not, until now, understand the phenomenon, mainly on exploring endoscopically the permeability of the whole aqueduct. In adults, we call this condition the functional trapped fourth ventricle because in none of our cases have we found physical obstruction of CSF flow. Third ventricle-fourth ventriculostomy is by far the most frequently used technique for cannulation of the aqueduct in a trapped fourth ventricle. In our reported cases, we have introduced a silicone tube stent from below after accessing the fourth ventricle through a small suboccipital craniectomy, ascending it on the aqueduct in order to reach the third ventricle. Management of this infrequently isolated fourth ventricle, but communicated with the rest of ventricular system, remains a challenge for neurosurgeons. Lack of knowledge of the pathophysiology makes it difficult to treat a problem that we do not understand.

Association of X-linked hydrocephalus and Hirschsprung disease: report of a new patient with a mutation in the L1CAM gene.

X-linked hydrocephalus (XLH) has an incidence of 1/30,000 male births and is characterized by intellectual disability, spastic paraplegia, adducted thumbs, and agenesis of corpus callosum, and/or corticospinal tract. The great proportion of cases is ascribed to loss of function mutations of L1CAM gene. Hirschsprung disease (HSCR) is characterized by the absence of ganglion cells in the submucosal and myenteric plexuses along a variable portion of the intestinal tract and has incidence of about 1/5,000. Although with several genes involved in its pathogenesis, the major HSCR gene is the RET proto-oncogene. To date only a few patients have been reported with both phenotypes and mutations in the L1CAM gene. In this report, we describe a new patient with concurrent XLH and HSCR. L1CAM mutational screening showed the presence of the G698R hemizygous mutation, which is a deleterious substitution affecting a key residue necessary for the correct folding of the protein. Moreover, the patient also carried the transcriptional enhancer RET mutation (c.73 + 9277T > C) in heterozygosis. We speculate that both the RET enhancer variant, and the L1CAM mutation may act in combination to produce the enteric phenotype, probably with the participation of other still unidentified molecular events. While it is obvious that additional studies are necessary to further delineate the association between XLH and HSCR in the presence of L1CAM mutations, the documentation of this new patient reinforces the role of this gene acting either in a direct or indirect way in the pathogenesis of Hirschsprung disease.

Hydrocephalus with Hirschsprung disease: severe end of X-linked hydrocephalus spectrum.

L1CAM molecule is a cell adhesion molecule in nervous and enteric systems and is responsible for X-linked hydrocephalus (XLH) spectrum, which is a rare condition with severe congenital hydrocephalus, dysgenesis of the corpus callosum, intellectual disability, spasticity, and adducted thumbs. Several cases of XLH accompanied by Hirschsprung disease (HSCR) have been reported in the literature, but whether HSCR results from a gain-of-function mutation in cases with XLH, i.e., a neomorphic mutation, or the severe end of the L1CAM mutation spectrum remains unclear. The present patient was a Japanese boy with severe congenital hydrocephalus with aqueductal stenosis as well as hypoplasia of the corpus callosum. HSCR had been confirmed by a biopsy. A mutation analysis of the L1CAM gene showed a C61T mutation in exon 1, resulting in a truncating nonsense mutation at amino acid position 21 and producing an extremely short protein that was unlikely to interact with other proteins. These findings suggest that XLH-HSCR represents the severe end of the XLH spectrum, rather than a neomorphic mutation. A thorough abdominal investigation to rule out HSCR should be considered in patients with XLH accompanied by severe constipation.

The aqueduct of Sylvius: a sonographic landmark for neural tube defects in the first trimester.

OBJECTIVES: To describe a new first-trimester sonographic landmark, posterior displacement of the midbrain and aqueduct of Sylvius, which may be useful in early screening for neural tube defects. METHODS: This was a prospective study of 457 normal fetuses at 11 + 0 to 13 + 6 weeks' gestation. We measured the distance from the posterior border of the aqueduct of Sylvius to the anterior border of the occiput (AOS-to-occiput distance) in the axial plane and created a reference range. In the nine fetuses with abnormal midbrain position identified in the first trimester and with neural tube defect subsequently confirmed, we analyzed ultrasound images to determine the position of the aqueduct of Sylvius. RESULTS: The lower limit of normal AOS-to-occiput distance (mean minus 2 SD) ranged from 1.7 mm at a crown-rump length (CRL) of 45 mm to 3.7 mm at a CRL of 84 mm. In the nine cases with abnormal position of the midbrain and confirmed neural tube defect, juxtaposition of the midbrain to the occiput was the clue to diagnosis of the spinal abnormality. In all nine cases, the AOS-to-occiput distance was below the established normal range. CONCLUSIONS: Examination of the midbrain in an axial plane may prove a reliable marker for the first-trimester diagnosis of neural tube defects. In contrast to recently reported subtle changes in the mid-sagittal view of the posterior cranial fossa, axial imaging of the midbrain reveals striking displacement of this structure, with virtual juxtaposition to the occiput, in fetuses with confirmed open spina bifida. This anatomical distortion of the midbrain can be quantified by measurement of the AOS-to-occiput distance.

Etiology and cranial CT scan profile of nontumoral hydrocephalus in a tertiary black African hospital.

OBJECT: Hydrocephalus is a common condition in the pediatric population. The cause of hydrocephalus, Evans ratio, ventricular index, and cerebral mantle thickness are some of the factors associated with poor surgical outcome. This study was conducted to evaluate the profile of these factors in the authors' patient population. METHODS: The authors conducted a prospective study from the August 1, 2006, to May 30, 2010. The consecutive patients were all 6 years of age or younger. The demographic information, cause of hydrocephalus, and cranial computerized measurements were taken (including widths of the frontal/occipital horns, third ventricle, and cerebral mantle thickness) and entered into the procedural forms. RESULTS: One hundred thirty-seven patients presented to the unit over the stipulated period. The male/female ratio was 1.1:1. The median age at presentation was 4 months (mean 7.3 months, range 4 days to 6 years). Myelomeningocele-associated hydrocephalus, aqueductal stenosis, and postmeningitic hydrocephalus accounted for 30.7%, 22.6%, and 17.5%, respectively, of the cases. The mean Evans ratio was 0.56 (range 0.43-0.70), the mean ventricular index was 197.18 (range 135.0-245.3), and the mean cerebral mantle was 10.8 mm (10-14 mm). CONCLUSIONS: This study shows that the congenital form of hydrocephalus is the predominant variety in the authors' population. Myelomeningocele-associated hydrocephalus, aqueductal stenosis, Dandy-Walker malformation, and postmeningitic hydrocephalus are common causes of hydrocephalus.

Coexistent intraventricular abnormalities in periventricular giant arachnoid cysts.

OBJECT: Arachnoid cysts are congenital lesions that arise during development by splitting of the arachnoid membrane. Large cysts can be adjacent to CSF pathways causing a marked midline shift and hydrocephalus. The association between a large arachnoid cyst and hydrocephalus has been commonly described as being due to a mass effect, but these previous reports have not focused closely on any associated intraventricular abnormalities. METHODS: Seven patients who were previously treated with a cystoperitoneal shunt presented with shunt failure, hydrocephalus, and/or cyst expansion. All of these patients had giant arachnoid cysts extending to the periventricular region from the original site, which was the sylvian fissure in 4 patients, and the suprasellar cistern, quadrigeminal cistern, and interhemispheric fissure in 1 patient each. Endoscopic exploration of the ventricular system and cyst fenestration was then performed in all patients. RESULTS: The endoscopic findings were obstruction of the cerebral aqueduct by a membrane not related to the cyst in 5 patients, occlusion of the foramen of Monro in 6, septum pellucidum hypoplasia in 2, and occlusion of the cerebral aqueduct by a quadrigeminal arachnoid cyst in 1. Endoscopic procedures performed were septum pellucidum fenestration and/or foraminoplasty in 5 patients, aqueductoplasty in 2, endoscopic third ventriculostomy in 5, fenestration of the lamina terminalis in 1, and direct cystocisternostomy in 1. After the endoscopic procedure, signs and symptoms of increased intracranial pressure and hydrocephalus improved in all patients, with a reduction in size of the cyst and the ventricle. CONCLUSIONS: Ventricular abnormalities contributing to hydrocephalus may be associated with arachnoid cysts. These abnormalities may more likely reflect a common origin than a casual relation. Foramen of Monro stenosis and cerebral aqueduct occlusion associated with an arachnoid cyst can be more frequent than has been previously believed. In cases of periventricular giant arachnoid cysts, endoscopic exploration is a good alternative for examining the ventricular system and identifying and treating CSF obstructions caused by and/or related to arachnoid cysts.