Loss of Katnal2 leads to ependymal ciliary hyperfunction and autism-related phenotypes in mice.

Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles. Katnal2-KO hippocampal neurons surrounded by enlarged lateral ventricles show progressive synaptic deficits that correlate with ASD-like transcriptomic changes involving synaptic gene down-regulation. Importantly, early postnatal Katnal2 re-expression prevents ciliary, ventricular, and behavioral phenotypes in Katnal2-KO adults, suggesting a causal relationship and a potential treatment. Therefore, Katnal2 negatively regulates ependymal ciliary function and its deletion in mice leads to ependymal ciliary hyperfunction and hydrocephalus accompanying ASD-related behavioral, synaptic, and transcriptomic changes.

Functional study of a rare L1CAM gene c.1759G>C variant prove its pathogenicity.

L1 syndrome, a neurological disorder with an X-linked inheritance pattern, mainly results from mutations occurring in the L1 cell adhesion molecule (L1CAM) gene. The L1CAM molecule, belonging to the immunoglobulin (Ig) superfamily of neurocyte adhesion molecules, plays a pivotal role in facilitating intercellular signal transmission across membranes and is indispensable for proper neuronal development and function. This study identified a rare missense variant (c.1759G>C; p.G587R) in the L1CAM gene within a male fetus presenting with hydrocephalus. Due to a lack of functional analysis, the significance of the L1CAM mutation c.1759G>C (p.G587R) remains unknown. We aimed to perform further verification for its pathogenicity. Blood samples were obtained from the proband and his parents for trio clinical exome sequencing and mutation analysis. Expression level analysis was conducted using western blot techniques. Immunofluorescence was employed to investigate L1CAM subcellular localization, while cell aggregation and cell scratch assays were utilized to assess protein function. The study showed that the mutation (c.1759G>C; p.G587R) affected posttranslational glycosylation modification and induced alterations in the subcellular localization of L1-G587R in the cells. It resulted in the diminished expression of L1CAM on the cell surface and accumulation in the endoplasmic reticulum. The p.G587R altered the function of L1CAM protein and reduced homophilic adhesion capacity of proteins, leading to impaired adhesion and migration of proteins between cells. Our findings provide first biological evidence for the association between the missense mutation (c.1759G>c; p.G587R) in the L1CAM gene and L1 syndrome, confirming the pathogenicity of this missense mutation.

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.

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.

Structural Alterations of the Corpus Callosum in Children With Infantile Hydrocephalus.

This study investigates structural alterations of the corpus callosum in children diagnosed with infantile hydrocephalus. We aim to assess both macrostructural (volume) and microstructural (diffusion tensor imaging metrics) facets of the corpus callosum, providing insights into the nature and extent of alterations associated with this condition. Eighteen patients with infantile hydrocephalus (mean age = 9 years) and 18 age- and sex-matched typically developing healthy children participated in the study. Structural magnetic resonance imaging and diffusion tensor imaging were used to assess corpus callosum volume and microstructure, respectively. Our findings reveal significant alterations in corpus callosum volume, particularly in the posterior area, as well as distinct microstructural disparities, notably pronounced in these same segments. These results highlight the intricate interplay between macrostructural and microstructural aspects in understanding the impact of infantile hydrocephalus. Examining these structural alterations provides an understanding into the mechanisms underlying the effects of infantile hydrocephalus on corpus callosum integrity, given its pivotal role in interhemispheric communication. This knowledge offers a more nuanced perspective on neurologic disorders and underscores the significance of investigating the corpus callosum's health in such contexts.

Expanding the phenotypic spectrum of LIG4 pathogenic variations: neuro-histopathological description of 4 fetuses with stenosis of the aqueduct.

Severe ventriculomegaly is a rare congenital brain defect, usually detected in utero, of poor neurodevelopmental prognosis. This ventricular enlargement can be the consequence of different mechanisms: either by a disruption of the cerebrospinal fluid circulation or abnormalities of its production/absorption. The aqueduct stenosis is one of the most frequent causes of obstructive ventriculomegaly, however, fewer than 10 genes have been linked to this condition and molecular bases remain often unknown. We report here 4 fetuses from 2 unrelated families presenting with ventriculomegaly at prenatal ultra-sonography as well as an aqueduct stenosis and skeletal abnormalities as revealed by fetal autopsy. Genome sequencing identified biallelic pathogenic variations in LIG4, a DNA-repair gene responsible for the LIG4 syndrome which associates a wide range of clinical manifestations including developmental delay, microcephaly, short stature, radiation hypersensitivity and immunodeficiency. Thus, not only this report expands the phenotype spectrum of LIG4-related disorders, adding ventriculomegaly due to aqueduct stenosis, but we also provide the first neuropathological description of fetuses carrying LIG4 pathogenic biallelic variations.

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.

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.

Neuroimaging Findings in Fetal Hemimegalencephaly: Case Study and Review.

BACKGROUND: Limited information exists in the prenatal literature regarding the neuroimaging features of fetal hemimegalencephaly. SUMMARY: This report describes ultrasound and magnetic resonance imaging (MRI) findings in a second-trimester fetus with an isolated, severe form of hemimegalencephaly. The most prominent imaging findings included unilateral enlarged cerebral hemisphere and ipsilateral ventriculomegaly causing cerebral asymmetry, midline shift, and macrocephaly. Abnormal cortical development imaging signs were also evident. A literature review encompassing 23 reports describing 36 cases, including ours, is presented. KEY MESSAGES: Characteristic ultrasound findings for the diagnosis of hemimegalencephaly are not always apparent prenatally. Asymmetric ventriculomegaly emerges as the most common but nonspecific presenting feature during routine second- or third-trimester ultrasound scans. Subsequent high-resolution prenatal neurosonography and fetal MRI facilitate definitive prenatal diagnosis, showcasting associated features primarily related to cortical migration, differentiation, and maturation. Postnatally, the prognosis is poor due to intractable seizures, hemiplegia, and progressive neurodevelopmental delay.

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.