A de novo pathogenic variant in DHX30 gene in a fetus with isolated dysgenesis of the corpus callosum.

A 36 years old woman in her first pregnancy was referred at 24w3d for a dedicated neurosonographic examination due to a suspected short corpus callosum (CC). The examination depicted a dysgenetic CC with asymmetric thickness at the level of the body in coronal views, very thin in the midline and thicker in both sides, suggesting bilateral formation of Probst bundles. The BPD, HC, and transverse cerebellar diameters were in the normal low range without associated growth restriction. Associated anomalies were not detected in the brain or other organs. Following genetic consultation and a normal CMA, trio exome sequencing was performed and a de novo missense pathogenic mutation c.2353 C > T in the DHX30 gene was detected. This variant has been previously reported in children and adults, mostly with a severe phenotype including neurodevelopmental disorder with variable motor and language impairment, but also mild phenotypes have been reported. MRI describes delayed myelination, ventriculomegaly, and cortical and cerebellar atrophy as imaging features in affected patients. This is the first prenatal report of a DHX30-associated neurodevelopmental disorder in which the fetus presents with isolated callosal dysgenesis, stressing the importance of exome sequencing in fetuses with this condition, as far as it is phenotypic presentation of numerous syndromes with different outcomes.

Stereotactic anatomy of the third ventricle.

PURPOSE: Endoscopic third ventriculostomy (ETV) is a surgical procedure that can lead to complications and requires detailed preoperative planning. This study aimed to provide a more accurate understanding of the anatomy of the third ventricle and the location of important structures to improve the safety and success of ETV. METHODS: We measured the stereotactic coordinates of six points of interest relative to a predefined stereotactic reference point in 23 cadaver brain hemi-sections, 200 normal brain magnetic resonance imaging (MRI) scans, and 24 hydrocephalic brain MRI scans. The measurements were statistically analyzed, and comparisons were made. RESULTS: We found some statistically significant differences between genders in MRIs from healthy subjects. We also found statistically significant differences between MRIs from healthy subjects and both cadaver brains and MRIs with hydrocephalus, though their magnitude is very small and not clinically relevant. Some stereotactic points were more posteriorly and inferiorly located in cadaver brains, particularly the infundibular recess and the basilar artery. It was found that all stereotactic points studied were more posteriorly located in brains with hydrocephalus. CONCLUSION: The study describes periventricular structures in cadaver brains and MRI scans from healthy and hydrocephalic subjects, which can guide neurosurgeons in planning surgical approaches to the third ventricle. Overall, the study contributes to understanding ETV and provides insights for improving its safety and efficacy. The findings also support that practicing on cadaveric brains can still provide valuable information and is valid for study and training of neurosurgeons unfamiliar with the ETV technique.

A Review of Cerebrospinal Fluid Circulation and the Pathogenesis of Congenital Hydrocephalus.

The brain's ventricles are filled with a colorless fluid known as cerebrospinal fluid (CSF). When there is an excessive accumulation of CSF in the ventricles, it can result in high intracranial pressure, ventricular enlargement, and compression of the surrounding brain tissue, leading to potential damage. This condition is referred to as hydrocephalus. Hydrocephalus is classified into two categories: congenital and acquired. Congenital hydrocephalus (CH) poses significant challenges for affected children and their families, particularly in resource-poor countries. Recognizing the psychological and economic impacts is crucial for developing interventions and support systems that can help alleviate the distress and burden faced by these families. As our understanding of CSF production and circulation improves, we are gaining clearer insights into the causes of CH. In this article, we will summarize the current knowledge regarding CSF circulation pathways and the underlying causes of CH. The main causes of CH include abnormalities in the FoxJ1 pathway of ventricular cilia, dysfunctions in the choroid plexus transporter Na+-K+-2Cl- contransporter isoform 1, developmental abnormalities in the cerebral cortex, and structural abnormalities within the brain. Understanding the causes of CH is indeed crucial for advancing research and developing effective treatment strategies. In this review, we will summarize the findings from existing studies on the causes of CH and propose potential research directions to further our understanding of this condition.

Successful Surgical Resection of an Ependymal Cyst in the Fourth Ventricle of a Dog.

Ependymal cysts represent congenital brain malformations rarely described in human medicine, where surgical resection is the treatment of choice. In veterinary medicine, only three cases have been previously reported, with one partially resected with surgery. A 6 yr old entire male American Staffordshire terrier was referred with a 4 mo history of incoordination and collapsing episodes with extensor rigidity. Neurological examination localized the lesion to the left central vestibular system and cerebellum. A brain computed tomography scan showed a hypoattenuating lesion with peripheral contrast enhancement in the fourth ventricle consistent with a cyst and secondary hydrocephalus. Treatment with prednisone was initiated, but despite an initial improvement, neurologic signs recurred and a suboccipital craniectomy to remove the cyst was performed. The cyst was first drained, and the capsule was carefully resected. The histopathological evaluation revealed a simple cubic to cylindrical epithelium with apical cilia and loose surrounding fibrillar tissue consistent with an intraventricular ependymal cyst. Four and a half years after surgery, the dog only shows short episodes of balance loss when turning abruptly but is otherwise neurologically normal. To the authors' knowledge, this is the first reported ependymal cyst in the fourth ventricle of a dog with successful surgical resection.

Clinical Indications for Rapid Sequence MRI in Pediatric Neurosurgical Patients and the Limitations and Barriers to Implementation.

Rapid and fast magnetic resonance imaging (MRI) protocols have become increasingly popular for pediatric neurosurgical patients as they are a great way to reduce ionizing radiation and sedation. While their popularity has increased, there are hurdles to overcome when transitioning to using them clinically, such as cost, staffing training, and motion artifact. Through this paper, we developed a protocol for clinical applications where rapid MRI can be a substitute or adjuvant in diagnostic workup. Further, we outline the relevant literature for the use of RS-MRI for the spine, TBI, and hydrocephalus pathologies while expanding upon the limitations and logistical barriers when transitioning to their use, a few of which are discussed above. Through this, we conclude that RS-MRI can be used diagnostically for spinal pathologies such as syrinx and hydrocephalus. Further, its lack of sensitivity for TBI findings makes rapid sequence magnetic resonance imaging (RS-MRI) a strong adjuvant with other advanced imaging or computed tomography (CT) for traumatic brain injury (TBI) pathologies.

Balamuthia mandrillaris amoebic encephalitis mimicking tuberculous meningitis.

A 76-year-old female with no apparent immunosuppressive conditions and no history of exposure to freshwater and international travel presented with headache and nausea 3 weeks before the presentation. On admission, her consciousness was E4V4V6. Cerebrospinal fluid analysis showed pleocytosis with mononuclear cell predominance, elevated protein, and decreased glucose. Despite antibiotic and antiviral therapy, her consciousness and neck stiffness gradually worsened, right eye-movement restriction appeared, and the right direct light reflex became absent. Brain magnetic resonance imaging revealed hydrocephalus in the inferior horn of the left lateral ventricle and meningeal enhancement around the brainstem and cerebellum. Tuberculous meningitis was suspected, and pyrazinamide, ethambutol, rifampicin, isoniazid, and dexamethasone were started. In addition, endoscopic biopsy was performed from the white matter around the inferior horn of the left lateral ventricle to exclude brain tumor. A brain biopsy specimen revealed eosinophilic round cytoplasm with vacuoles around blood vessels, and we diagnosed with amoebic encephalitis. We started azithromycin, flucytosine, rifampicin, and fluconazole, but her symptoms did not improve. She died 42 days after admission. In autopsy, the brain had not retained its structure due to autolysis. Hematoxylin and eosin staining of her brain biopsy specimen showed numerous amoebic cysts in the perivascular brain tissue. Analysis of the 16S ribosomal RNA region of amoebas from brain biopsy and autopsy specimens revealed a sequence consistent with Balamuthia mandrillaris. Amoebic meningoencephalitis can present with features characteristic of tuberculous meningitis, such as cranial nerve palsies, hydrocephalus, and basal meningeal enhancement. Difficulties in diagnosing amoebic meningoencephalitis are attributed to the following factors: (1) excluding tuberculous meningitis by microbial testing is difficult, (2) amoebic meningoencephalitis has low incidence and can occur without obvious exposure history, (3) invasive brain biopsy is essential in diagnosing amoebic meningoencephalitis. We should recognize the possibility of amoebic meningoencephalitis when evidence of tuberculosis meningitis cannot be demonstrated.

Choroid plexus mast cells drive tumor-associated hydrocephalus.

Tumor-associated hydrocephalus (TAH) is a common and lethal complication of brain metastases. Although other factors beyond mechanical obstructions have been suggested, the exact mechanisms are unknown. Using single-nucleus RNA sequencing and spatial transcriptomics, we find that a distinct population of mast cells locate in the choroid plexus and dramatically increase during TAH. Genetic fate tracing and intracranial mast-cell-specific tryptase knockout showed that choroid plexus mast cells (CPMCs) disrupt cilia of choroid plexus epithelia via the tryptase-PAR2-FoxJ1 pathway and consequently increase cerebrospinal fluid production. Mast cells are also found in the human choroid plexus. Levels of tryptase in cerebrospinal fluid are closely associated with clinical severity of TAH. BMS-262084, an inhibitor of tryptase, can cross the blood-brain barrier, inhibit TAH in vivo, and alleviate mast-cell-induced damage of epithelial cilia in a human pluripotent stem-cell-derived choroid plexus organoid model. Collectively, we uncover the function of CPMCs and provide an attractive therapy for TAH.

Hydrocephalus in patients with vestibular schwannoma.

BACKGROUND: Hydrocephalus (HC) is common in patients with vestibular schwannoma (VS). This can be managed with a cerebrospinal fluid (CSF) diversion procedure prior to VS resection or with VS resection, keeping CSF diversion in reserve unless required postoperatively. No clear consensus exists as to which approach is superior. This study identifies factors predictive of the development of HC, and analyses outcomes for those managed with primary CSF resection versus tumour resection. METHODS: Single-centre retrospective cohort study of 204 consecutive adult patients with a unilateral VS from May 2009 to June 2021. Data was collected on patient and tumour demographics, management, and outcome. RESULTS: 204 patients, with a mean age at presentation of 59.5 (21-83), with 50% female, and a mean follow-up of 7.5 years (1.8-13.9) were included. 119 were managed conservatively, 36 with stereotactic radiosurgery only, and 49 with surgery. 30 (15%) patients had radiological HC, of which 23 (77%) were obstructive, and 7 (23%) were communicating. Maximum intracranial tumour diameter and Koos grade were higher in patients with HC. Of the patients with HC the majority (20, 67%) were managed initially with CSF diversion, with 12 patients undergoing subsequent tumour resection, and three patients avoiding primary resection. Nine (30%) were managed with primary surgical resection, of whom three required subsequent CSF diversion. Complication rates and Modified Rankin Scale (MRS) were comparable or lower in the CSF diversion group (8%, MRS ≤2 = 83%), versus the primary resection group (67%, MRS ≤2 = 67%), and the primary surgical resection without HC group (25%, MRS ≤2 = 86%). CONCLUSIONS: CSF diversion prior to tumour resection is a safe and acceptable strategy compared to primary VS resection, with improved outcomes and reduced surgical complications. Randomized studies and national databases are needed to determine the long-term outcomes of patients treated with CSF diversion versus primary resection.

Pineal/germ cell tumors and pineal parenchymal tumors.

INTRODUCTION: Pineal region tumors (PRTs) are tumors arising from the pineal gland and the paraspinal structures. These tumors are rare and heterogeneous that account for 2.8-10.1% and 0.6-3.2% of tumors in children and in all ages, respectively. Almost all types and subtypes of CNS tumors may be diagnosed in this region. These tumors come from cells of the pineal gland (pinealocytes and neuroglial cells), ectopic primordial germ cells (PGC), and cells from adjacent structures. Hence, PRTs are consisted of pineal parenchyma tumors (PPTs), germ cell tumors (GCTs), neuroepithelial tumors (NETs), other miscellaneous types of tumors, cystic tumors (epidermoid, dermoid), and pineal cyst in addition. The symptoms of PRTs correlate to the increased intracranial cranial pressure due to obstructive hydrocephalus and dorsal midbrain compression. The diagnostic imaging studies are mainly MRI of brain (with and without gadolinium) along with a sagittal view of whole spine. Serum and/or CSF AFP/ß-HCG helps to identify GCTs. The treatment of PRTs is consisted of the selection of surgical biopsy/resection, handling of hydrocephalus, neoadjuvant and/or adjuvant therapy according to age, tumor location, histopathological/molecular classification, grading of tumors, staging, and threshold value of markers (for GCTs) in addition. METHODS: In this article, we review the following focus points: 1. Background of pineal region tumors. 2. Pineal GCTs and evolution of management. 3. Molecular study for GCTs and pineal parenchymal tumors. 4. Review of surgical approaches to the pineal region. 5. Contribution of endoscopy. 6. Adjuvant therapy (chemotherapy, radiotherapy, and combination). 7. RESULTS: In all ages, the leading three types of PRTs in western countries were PPTs (22.7-34.8%), GCTs (27.3-34.4%), and NETs (17.2-28%). In children and young adults, the leading PRTs were invariably in the order of GCTs (40-80.5%), PPTs (7.6-21.6%), NETs (2.4-37.5%). Surgical biopsy/resection of PRTs is important for precision diagnosis and therapy. Safe resection with acceptable low mortality and morbidity was achieved after 1970s because of the advancement of surgical approaches, CSF shunt and valve system, microscopic and endoscopic surgery. Following histopathological diagnosis and classification of types and subtypes of PRTs, in PPTs, through molecular profiling, four molecular groups of pineoblastoma (PB) and their oncogenic driver were identified. Hence, molecular stratified precision therapy can be achieved. CONCLUSION: Modern endoscopic and microsurgical approaches help to achieve precise histopathological diagnosis and molecular classification of different types and subtypes of pineal region tumors for risk-stratified optimal, effective, and protective therapy. In the future, molecular analysis of biospecimen (CSF and blood) along with AI radiomics on tumor imaging integrating clinical and bioinformation may help for personalized and risk-stratified management of patients with pineal region tumors.

Chiasmal Compression by the Third Ventricle in Obstructive Hydrocephalus: Case Report and Review of the Literature.

The authors review the phenomenon of third ventricular dilation causing chiasmal compression and vision loss, emphasize the need for further study given continued poor outcomes, and, in a patient case, illustrate the value of obtaining magnetic resonance imaging and nerve and macular optical coherence tomography in a patient with an unclear mechanism of vision loss. [J Pediatr Ophthalmol Strabismus. 2023;60(5):e49-e54.].

Celecoxib attenuates neuroinflammation, reactive astrogliosis and promotes neuroprotection in young rats with experimental hydrocephalus.

Hydrocephalus is a neurological condition with altered cerebrospinal fluid flow (CSF). The treatment is surgical and the most commonly used procedure is ventricle-peritoneal shunt. However, not all patients can undergo immediate surgery or achieve complete lesion reversal. Neuroprotective measures are valuable in such cases. It was evaluated whether the use of celecoxib, a selective inhibitor of COX-2, associated or not with ventricular-subcutaneous derivation, could offer benefits to the brain structures affected by experimental hydrocephalus. Seven-day-old male Wistar Hannover rats induced by intracisternal injection of kaolin 15% were used, divided into five groups with ten animals each: intact control (C), untreated hydrocephalus (H), hydrocephalus treated with celecoxib 20 mg/kg intraperitoneal (HTC), hydrocephalus treated with shunt (HTS) and hydrocephalus treated with shunt and celecoxib 20 mg/kg intraperitoneal (HTCS). Celecoxib was administered for 21 consecutive days, starting the day after hydrocephalus induction and continuing until the end of the experimental period. The surgery was performed seven days after inducing hydrocephalus. Multiple assessment methods were used, such as behavioral tests (water maze and open field), histological analysis (hematoxylin and eosin), immunohistochemistry (caspase-3, COX-2, and GFAP), and ELISA analysis of GFAP. The results of the behavioral and memory tests indicated that celecoxib improves the neurobehavioral response. The improvement can be attributed to the reduced neuroinflammation (p < 0.05), and astrogliosis (p < 0.05) in different brain regions. In conclusion, the results suggest that celecoxib holds great potential as an adjuvant neuroprotective drug for the treatment of experimental hydrocephalus.

Spontaneously hypertensive rats can become hydrocephalic despite undisturbed secretion and drainage of cerebrospinal fluid.

BACKGROUND: Hydrocephalus constitutes a complex neurological condition of heterogeneous origin characterized by excessive cerebrospinal fluid (CSF) accumulation within the brain ventricles. The condition may dangerously elevate the intracranial pressure (ICP) and cause severe neurological impairments. Pharmacotherapies are currently unavailable and treatment options remain limited to surgical CSF diversion, which follows from our incomplete understanding of the hydrocephalus pathogenesis. Here, we aimed to elucidate the molecular mechanisms underlying development of hydrocephalus in spontaneously hypertensive rats (SHRs), which develop non-obstructive hydrocephalus without the need for surgical induction. METHODS: Magnetic resonance imaging was employed to delineate brain and CSF volumes in SHRs and control Wistar-Kyoto (WKY) rats. Brain water content was determined from wet and dry brain weights. CSF dynamics related to hydrocephalus formation in SHRs were explored in vivo by quantifying CSF production rates, ICP, and CSF outflow resistance. Associated choroid plexus alterations were elucidated with immunofluorescence, western blotting, and through use of an ex vivo radio-isotope flux assay. RESULTS: SHRs displayed brain water accumulation and enlarged lateral ventricles, in part compensated for by a smaller brain volume. The SHR choroid plexus demonstrated increased phosphorylation of the Na+/K+/2Cl- cotransporter NKCC1, a key contributor to choroid plexus CSF secretion. However, neither CSF production rate, ICP, nor CSF outflow resistance appeared elevated in SHRs when compared to WKY rats. CONCLUSION: Hydrocephalus development in SHRs does not associate with elevated ICP and does not require increased CSF secretion or inefficient CSF drainage. SHR hydrocephalus thus represents a type of hydrocephalus that is not life threatening and that occurs by unknown disturbances to the CSF dynamics.

Benign and Malignant Tumors of the Pineal Region.

Pineal region tumors fall into five broad categories: benign pineal region tumors, glial tumors, papillary tumors, pineal parenchymal tumors, and germ cell tumors. Genetic and transcriptional studies have identified key chromosomal alterations in germinomas (RUNDC3A, ASAH1, LPL) and in pineocytomas/pineoblastomas (DROSHA/DICER1, RB1). Pineal region tumors generally present with symptoms of hydrocephalus including nausea, vomiting, papilledema, and the classical Parinaud's triad of upgaze paralysis, convergence-retraction nystagmus, and light-near pupillary dissociation. Workup requires neuroimaging and tissue diagnosis via biopsy. In germinoma cases, diagnosis may be made based on serum or CSF studies for alpha-fetoprotein or beta-HCG making the preferred treatment radiosurgery, thereby preventing the need for unnecessary surgeries. Treatment generally involves three steps: CSF diversion in cases of hydrocephalus, biopsy through endoscopic or stereotactic methods, and open surgical resection. Multiple surgical approaches are possible for approach to the pineal region. The original approach to the pineal region was the interhemispheric transcallosal first described by Dandy. The most common approach is the supracerebellar infratentorial approach as it utilizes a natural anatomic corridor for access to the pineal region. The paramedian or lateral supracerebellar infratentorial approach is another improvement that uses a similar anatomic corridor but allows for preservation of midline bridging veins; this minimizes the chance for brainstem or cerebellar venous infarction. Determination of the optimal approach relies on tumor characteristics, namely location of deep venous structures to the tumor along with the lateral eccentricity of the tumor. The immediate post-operative period is important as hemorrhage or swelling can cause obstructive hydrocephalus and lead to rapid deterioration. Adjuvant therapy, whether chemotherapy or radiation, is based on tumor pathology. Improvements within pineal surgery will require improved technology for access to the pineal region along with targeted therapies that can effectively treat and prevent recurrence of malignant pineal region tumors.

Methods to study motile ciliated cell types in the zebrafish brain.

Cilia are well conserved hair-like structures that have diverse sensory and motile functions. In the brain, motile ciliated cells, known as ependymal cells, line the cerebrospinal fluid (CSF) filled ventricles, where their beating contribute to fluid movement. Ependymal cells have gathered increasing interest since they are associated with hydrocephalus, a neurological condition with ventricular enlargement. In this article, we highlight methods to identify and characterize motile ciliated ependymal lineage in the brain of zebrafish using histological staining and transgenic reporter lines.

Extra-axial Endoscopic Third Ventriculostomy: A Novel Treatment for Managing Hydrocephalus Due to Vertebrobasilar Dolichoectasia.

BACKGROUND: Vertebrobasilar dolichoectasia, a rare vascular anomaly, rarely presents with hydrocephalus. The traditional treatment for hydrocephalus is a ventriculoperitoneal shunt. Conventional endoscopic third ventriculostomy can avoid shunt-related complications but is considered risky due to the presence of the dolichoectatic vessel. A subfrontal extra-axial fenestration of the lamina terminalis can circumvent this anatomic constraint and establish cerebrospinal fluid communication between the third ventricle and subarachnoid space. METHODS: We performed an extra-axial endoscopic third ventriculostomy to manage hydrocephalus due to vertebrobasilar dolichoectasia in a 26-year-old male. The clinical description, surgical technique, outcome, and rationale are described. RESULTS: The patient had symptomatic improvement in his headaches and vision. There was also improvement in the postoperative ventricular indices: Evans index-19% reduction, frontal occipital horn ratio-14.1% reduction, and third ventricle index-39.5% reduction. A cine-phase magnetic resonance image showed cerebrospinal fluid flow void through the lamina terminalis fenestration, suggesting patency. CONCLUSIONS: Extra-axial endoscopic third ventriculostomy may be a suitable treatment alternative to circumvent anatomic constraints produced by vertebrobasilar dolichoectasia in performing conventional endoscopic third ventriculostomy.

Establishment of Age- and Sex-Specific Reference Cerebral Ventricle Volumes.

BACKGROUND: The diagnosis of hydrocephalus is dependent on clinical symptoms and radiographic findings including ventriculomegaly. Our goal was to generate a data set of ventricular volume utilizing non-pathologic computed tomography (CT) scans for adults to help define reference ventricle size. METHODS: We performed a retrospective analysis of non-contrast head CTs for adults at a single institution to identify patients who had undergone imaging and did not have a diagnosis of hydrocephalus, history of ventriculoperitoneal shunting, or treatments for hydrocephalus. A convolutional neural network was trained on hand-segmented scans from a variety of age ranges and then utilized to automate the segmentation of the entire data set. RESULTS: Ventricles on 866 CT scans were segmented to generate a reference range of volumes for both male and female individuals ranging in age from 18-99 years. The generated data were binned by age ranges. CONCLUSIONS: We have developed a convolutional neural network that can segment the ventricles on CT scans of adult patients over a range of ages. This network was used to measure the ventricular volume of non-pathologic head CTs to produce reference ranges for several age bins. This data set could be utilized to aid in the diagnosis of hydrocephalus by comparing potentially pathologic scans to reference ventricular volumes.

Ependymal polarity defects coupled with disorganized ciliary beating drive abnormal cerebrospinal fluid flow and spine curvature in zebrafish.

Idiopathic scoliosis (IS) is the most common spinal deformity diagnosed in childhood or early adolescence, while the underlying pathogenesis of this serious condition remains largely unknown. Here, we report zebrafish ccdc57 mutants exhibiting scoliosis during late development, similar to that observed in human adolescent idiopathic scoliosis (AIS). Zebrafish ccdc57 mutants developed hydrocephalus due to cerebrospinal fluid (CSF) flow defects caused by uncoordinated cilia beating in ependymal cells. Mechanistically, Ccdc57 localizes to ciliary basal bodies and controls the planar polarity of ependymal cells through regulating the organization of microtubule networks and proper positioning of basal bodies. Interestingly, ependymal cell polarity defects were first observed in ccdc57 mutants at approximately 17 days postfertilization, the same time when scoliosis became apparent and prior to multiciliated ependymal cell maturation. We further showed that mutant spinal cord exhibited altered expression pattern of the Urotensin neuropeptides, in consistent with the curvature of the spine. Strikingly, human IS patients also displayed abnormal Urotensin signaling in paraspinal muscles. Altogether, our data suggest that ependymal polarity defects are one of the earliest sign of scoliosis in zebrafish and disclose the essential and conserved roles of Urotensin signaling during scoliosis progression.

Bi-allelic variations in CRB2, encoding the crumbs cell polarity complex component 2, lead to non-communicating hydrocephalus due to atresia of the aqueduct of sylvius and central canal of the medulla.

Congenital hydrocephalus is a common condition caused by the accumulation of cerebrospinal fluid in the ventricular system. Four major genes are currently known to be causally involved in hydrocephalus, either isolated or as a common clinical feature: L1CAM, AP1S2, MPDZ and CCDC88C. Here, we report 3 cases from 2 families with congenital hydrocephalus due to bi-allelic variations in CRB2, a gene previously reported to cause nephrotic syndrome, variably associated with hydrocephalus. While 2 cases presented with renal cysts, one case presented with isolated hydrocephalus. Neurohistopathological analysis allowed us to demonstrate that, contrary to what was previously proposed, the pathological mechanisms underlying hydrocephalus secondary to CRB2 variations are not due to stenosis but to atresia of both Sylvius Aqueduct and central medullar canal. While CRB2 has been largely shown crucial for apico-basal polarity, immunolabelling experiments in our fetal cases showed normal localization and level of PAR complex components (PKCι and PKCζ) as well as of tight (ZO-1) and adherens (ß-catenin and N-Cadherin) junction molecules indicating a priori normal apicobasal polarity and cell-cell adhesion of the ventricular epithelium suggesting another pathological mechanism. Interestingly, atresia but not stenosis of Sylvius aqueduct was also described in cases with variations in MPDZ and CCDC88C encoding proteins previously linked functionally to the Crumbs (CRB) polarity complex, and all 3 being more recently involved in apical constriction, a process crucial for the formation of the central medullar canal. Overall, our findings argue for a common mechanism of CRB2, MPDZ and CCDC88C variations that might lead to abnormal apical constriction of the ventricular cells of the neural tube that will form the ependymal cells lining the definitive central canal of the medulla. Our study thus highlights that hydrocephalus related to CRB2, MPDZ and CCDC88C constitutes a separate pathogenic group of congenital non-communicating hydrocephalus with atresia of both Sylvius aqueduct and central canal of the medulla.

Concomitant, Single Burr Hole Endoscopic Third Ventriculostomy and Tumor Biopsy for Pineal Lesions: Feasibility, Safety, and Benefits.

Obtaining a prompt diagnosis, avoiding indwelling ventriculoperitoneal shunt, and enhancing the predictive value of pathologic examinations are only some of the advantages conferred by a simultaneous third ventriculostomy and tumor biopsy in patients with pineal region tumors. The objective of this study was to retrospectively search the literature on concomitant, single burr hole endoscopic third ventriculostomy (ETV) and tumor biopsy (TB) for pineal region tumors and to analyze the feasibility, surgical safety, and benefits of these 2 combined procedures. Consequently, a comprehensive, systematic literature search was performed in compliance with the updated PRISMA 2020 guidelines within electronic databases MEDLINE/PubMed, EMBASE, PLOS, and Cochrane Library. Statistical analysis was performed with IBM SPSS 28.0.1.1(14), using Kendall's and Spearman's tests, with a P < 0.05 considered significant. A total of 25 studies were selected and included in this review, for a total of 368 patients (mean age 20.6 years; range 1-86 years; SD 17.5). More than two-thirds of the procedures were operated with a rigid endoscope and 27.6% were performed with either a flexible endoscope, a combination of the 2, or not otherwise specified. Germinoma represented the most frequent diagnosis (20.1%) followed by astrocytoma (12.9%) and pineocytoma (9.9%). The single-entry approach allowed a correct histologic diagnosis in 88.7% of the examined cases. Summing up, concomitant ETV and TB represent a valuable option for the management of non-communicating hydrocephalus and the initial assessment of pineal region tumors. The histologic confirmation rate was 88.7% in the examined cohort, with only 10% of the biopsies yielding inconclusive results.