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.

Cerebrospinal Fluid Flow in Patients with Huntington's Disease.

OBJECTIVE: Investigations of cerebrospinal fluid (CSF) flow aberrations in Huntington's disease (HD) are of growing interest, as impaired CSF flow may contribute to mutant Huntington retention and observed heterogeneous responsiveness to intrathecally administered therapies. METHOD: We assessed net cerebral aqueduct CSF flow and velocity in 29 HD participants (17 premanifest and 12 manifest) and 51 age- and sex matched non-HD control participants using 3-Tesla magnetic resonance imaging methods. Regression models were applied to test hypotheses regarding: (i) net CSF flow and cohort, (ii) net CSF flow and disease severity (CAP-score), and (iii) CSF volume after correcting for age and sex. RESULTS: Group-wise analyses support a decrease in net CSF flow in HD (mean 0.14 ± 0.27 mL/min) relative to control (mean 0.32 ± 0.20 mL/min) participants (p = 0.02), with lowest flow in the manifest HD cohort (mean 0.04 ± 0.25 mL/min). This finding was explained by hyperdynamic CSF movement, manifesting as higher caudal systolic CSF flow velocity and higher diastolic cranial CSF flow velocity across the cardiac cycle, in HD (caudal flow: 0.17 ± 0.07 mL/s, cranial flow: 0.14 ± 0.08 mL/s) compared to control (caudal flow: 0.13 ± 0.06 mL/s, cranial flow: 0.11 ± 0.04 mL/s) participants. A positive correlation between cranial diastolic flow and disease severity was observed (p = 0.02). INTERPRETATIONS: Findings support aqueductal CSF flow dynamics changing with disease severity in HD. These accelerated changes are consistent with changes observed over the typical adult lifespan, and may have relevance to mutant Huntington retention and intrathecally administered therapeutics responsiveness. ANN NEUROL 2023;94:885-894.

Keyhole Aqueduct Syndrome.

Keyhole aqueduct syndrome is a rare progressive neurodegenerative disorder describing a unique set of neuro-ophthalmologic, neuroimaging, and histopathological findings on autopsy. A midline mesencephalic cleft communicating with the cerebral aqueduct resembling syrinx is seen on imaging and histopathology. There are 9 cases published in the literature. We encountered a patient with vertical nystagmus, internuclear ophthalmoplegia, and progressive ataxia who has a midline cleft connecting the cerebral aqueduct with the interpeduncular cistern highlighting a distinguishing feature of this syndrome.

CSF and venous blood flow from childhood to adulthood studied by real-time phase-contrast MRI.

PURPOSE: In vivo measurements of CSF and venous flow using real-time phase-contrast (RT-PC) MRI facilitate new insights into the dynamics and physiology of both fluid systems. In clinical practice, however, use of RT-PC MRI is still limited. Because many forms of hydrocephalus manifest in infancy and childhood, it is a prerequisite to investigate normal flow parameters during this period to assess pathologies of CSF circulation. This study aims to establish reference values of CSF and venous flow in healthy subjects using RT-PC MRI and to determine their age dependency. METHODS: RT-PC MRI was performed in 44 healthy volunteers (20 females, age 5-40 years). CSF flow was quantified at the aqueduct (Aqd), cervical (C3) and lumbar (L3) spinal levels. Venous flow measurements comprised epidural veins, internal jugular veins and inferior vena cava. Parameters analyzed were peak velocity, net flow, pulsatility, and area of region of interest (ROI). STATISTICAL TESTS: linear regression, student's t-test and analysis of variance (ANOVA). RESULTS: In adults volunteers, no significant changes in flow parameters were observed. In contrast, pediatric subjects exhibited a significant age-dependent decrease of CSF net flow and pulsatility in Aqd, C3 and L3. Several venous flow parameters decreased significantly over age at C3 and changed more variably at L3. CONCLUSION: Flow parameters varies depending on anatomical location and age. We established changes of brain and spinal fluid dynamics over an age range from 5-40 years. The application of RT-PC MRI in clinical care may improve our understanding of CSF flow pathology in individual patients.

Endoscopic transaqueductal stent placement for tumor-related aqueductal compression in pediatric patients: surgical consideration, technique, and results.

PURPOSE: Endoscopic transaqueductal stenting has become a well-accepted treatment option for a selected small subset of aqueductal stenosis-related obstructive hydrocephalus. However, transaqueductal stenting poses unique challenges and risks which requires critical consideration. This report discusses the clinical experiences with transaqueductal stenting for periaqueductal tumor-related aqueductal stenosis focusing on pediatric patients. METHODS: A retrospective analysis of all patients undergoing endoscopic TAS from 01/1993 to 01/2022 in the author's departments was performed. Demographic, clinical, radiological, and intraoperative endoscopic data were evaluated. All patients with AS-related occlusive hydrocephalus that was treated with TAS were analyzed and prospectively followed. Special attention has been given to providing insights into indications, surgical technique, and limitations. RESULTS: Out of 28 endoscopic transaqueductal endoscopis stenting procedures, five procedures were performed on periaqueductal tumor-related obstructive hydrocephalus, two children and three adult patients. CSF pathway was obstructed by tumor located in the aqueduct in 2, by tumor in the thalamus/mesencephalon in 1, by a tumor within the third ventricle in 1, and by a tumor of the lamina tecti in 1. Simultaneously with transaqueductal stenting, 2 endoscopic third ventriculostomies (ETV), 3 tumor biopsies, and 1 tumor resection were performed. Postoperative complications included the following: CSF fistula (1 case), and asymptomatic fornix contusion (1 case). A working aqueductal stent was achieved in all cases based on clinical follow-up evaluation. Postoperatively, all patients showed improvement or resolution of their symptoms. The mean follow-up period was 25.2 months (range, 1-108 months). One patient died due to tumor progression during early follow-up. No stent migration was seen. CONCLUSION: Endoscopic third ventriculostomy remains the gold standard for treatment of CSF circulation obstructions with lesions in the posterior third ventricle and aqueduct. Transaqueductal stenting for periaqueductal tumor-related aqueductal compression is technically feasible. However, because of the potential high risks and subtle advantages compared with ETV transaqueductal stenting, it might be indicated in a small subset of well-selected patients if alternative treatment options are not at hand.

The prepontine block and its relevance for the development and treatment of hydrocephalus.

OBJECTIVE: Pulsatile CSF flow patterns include flow through the ventricles to the subarachnoid space and cisterns and from the infra- to the supratentorial subarachnoid space. In this study, we demonstrate how an obstruction at the level of the prepontine space may lead to obstructive hydrocephalus with specific radiological characteristics, as well as the implications for treatment options. METHODS: We retrospectively collected data of patients who underwent surgery between February 2010 and December 2022 for hydrocephalus secondary to a suspected prepontine block. One additional patient diagnosed with prepontine block who did not undergo surgery was also included. We excluded patients with a background of previous unrelated neurosurgical procedures or CNS infections. RESULTS: Six children and two adults were included. Three presented with hydrocephalus on imaging, without any other underlying pathology. Five had a suprasellar arachnoid cyst, with its lower border abating the pons and occluding the spinal subarachnoid space (SAS). All cases had an open aqueduct on T2 sagittal sequences, as well as an infracerebellar or retrocerebellar CSF collection. In most cases, a horizontal web was identified in the prepontine region. Seven cases were treated with an endoscopic fenestration. One patient subsequently underwent a shunt surgery. All the operated children reached normal developmental milestones after surgery. CONCLUSIONS: This paper describes a rather small series of cases where clear obstruction was observed at the level of the prepontine subarachnoid space. We believe this anatomical subtlety adds to a better understanding of CSF pathways and the role of ETV in treating hydrocephalus, focusing on a small subgroup of patients without a clear obstruction.

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.

Advanced cerebrospinal fluid flow MRI findings of aqueductal stenosis caused by web.

BACKGROUND: The aqueductal web (AW) is one of the causes of aqueductus stenosis (AS). Recent advances in Magnetic resonance (MR) imaging have enabled us to better reveal the cerebrospinal fluid (CSF) flow dynamics and aqueductal anatomy. PURPOSE: The aim of this study is to evaluate the CSF flow dynamics of patients with AW with phase contrast Magnetic resonance imaging (MRI) and compare them with the imaging findings. MATERIALS AND METHODS: We evaluated 23 patients under 65-year-old age. On constructive interference in steady-state (T2 CISS) images, the width of prepontine cistern (PPC) and the width of Sylvian aqueduct (SA) were measured. Localization and number of webs were evaluated. The existence of flow at the aqueduct and the presence of spontaneous third ventriculostomy (STV) were evaluated on sagittal Sampling Perfection with Application optimized Contrast (SPACE) sequences. RESULTS: Of the 23 patients included in the study, 11 were male and 12 were female. The mean age was 34.02 (0.5-64). A total of 31 AWs were detected in 23 patients. Six of 23 patients (26.1%) had STV and 17 of those not. Four of 23 patients (17.4%) had aqueductal flow on SPACE sequences. The PPC distance was significantly wider in patients with STV (median: 6.7-4.5, interquartile range (IQR): 1.35, p = 0.004). In the cases where artifact secondary to flow is observed in SPACE sequences in aqueduct, the Evan index (EI) was significantly lower (median: 0.2955-0.3900, IQR: 0.03-0.14, p < 0.001). CONCLUSION: In patients with a low EI, there may be flow in the SA even if there is a web. In patients with a wide PPC distance, it is necessary to consider the presence of STV and evaluate the presence of flow with the SPACE sequences.

Trapped Fourth Ventricle: Pathophysiology, History and Treatment Strategies.

Trapped fourth ventricle is a clinic-radiological entity characterised by progressive neurological symptoms due to enlargement and dilatation of fourth ventricle secondary to obstruction to its outflow. There are several causative mechanisms for the development of trapped fourth ventricle, including previous haemorrhage, infection or inflammatory processes. However, this condition is most commonly observed in ex preterm paediatric patients shunted for a post-haemorrhagic or post-infective hydrocephalus. Until the introduction of endoscopic aqueductoplasty and stent placement, treatment of trapped fourth ventricle was associated with high rates of reoperation and complications resulting in morbidity. With the advent of new endoscopic techniques, supratentorial and infratentorial approaches for aqueductoplasty and stent insertion have revolutionised the treatment of trapped fourth ventricle. Fourth ventricular fenestration and direct shunting remain viable options in cases where aqueduct anatomy and length of obstruction is not surgically favourable for endoscopic approaches. In this book chapter, we explore the background, historical developments,$ and surgical treatment strategies in the management of this challenging condition.

Endoscopic fenestration of the superior medullary velum for the treatment of a trapped fourth ventricle-technical note.

A trapped fourth ventricle is a clinic-radiological entity characterised by progressive neurological symptoms due to an enlargement of the fourth ventricle secondary to obstruction to its outflow. This condition is most commonly observed in ex-preterm patients shunted for a post-haemorrhagic or post-infective hydrocephalus. Until the introduction of endoscopic aqueductoplasty and stent placement, through a supratentorial or an infratentorial approach, treatment of trapped fourth ventricle entailed high rates of complications, repeated procedures and consequent morbidity. We describe the first case of successful treatment of trapped fourth ventricle by fenestration of superior medullary velum through an infratentorial approach in a 20-month-old child with a functional supratentorial ventriculoperitoneal shunt and an aqueductal anatomy not favourable for stenting. To the best of our knowledge, this is the first reported case of utilisation of this technique in a patient with a trapped fourth ventricle, and we wish to highlight this new alternative approach in cases where conventional aqueductoplasty and stenting may not be feasible.

Late-onset obstructive hydrocephalus associated with occipital encephalocele with large skull defect successfully treated by endoscopic third ventriculostomy.

BACKGROUND: Hydrocephalus is one of the most common presentations of occipital encephaloceles and usually develops within the first year of life. This case report presents a rare case of late-onset obstructive hydrocephalus associated with occipital encephalocele with an extraordinarily large occipital skull defect. CASE REPORT: At birth, a newborn girl presented with an absence of a vast amount of occipital cranium and skin and was diagnosed with occipital hydroencephalomeningocele. Under meticulous sterile management, the affected area was successfully epithelialized, and the patient was discharged without infectious complication. Despite an obstructed cerebral aqueduct, she grew without any signs of hydrocephalus until the age of 7 years. Her gait gradually worsened, and imaging tests at the age of 8 years revealed markedly enlarged lateral and third ventricles but not the fourth ventricle. Endoscopic third ventriculostomy successfully relieved her symptoms with improvement of hydrocephalus. CONCLUSION: This is the first case of late-onset obstructive hydrocephalus associated with an occipital encephalocele characterized by large-scale cranial bony defects. Although further investigation is required to elucidate the mechanism of hydrocephalus, this rare phenomenon should be noted during neurological and radiological follow-up.

Influence of the area of the aqueduct and region of interest on quantification of stroke volume in healthy volunteers using phase-contrast cine magnetic resonance imaging.

BACKGROUND: Phase-contrast cine magnetic resonance imaging (PC-MRI) has been used to measure cerebrospinal fluid (CSF) flow dynamics, but the influence of the area of the aqueduct and region of interest (ROI) on quantification of stroke volume (SV) has not been assessed. PURPOSE: To assess the influence of the area of the ROI in quantifying the aqueductal SV measured with PC-MRI within the cerebral aqueduct. MATERIAL AND METHODS: Nine healthy volunteers (mean age = 29.6 years) were enrolled in the study, and brain MRI examinations were performed on a 3.0-T system. Quantitative analysis of the aqueductal CSF flow was performed using manual ROI placement. ROIs were separately drawn for each of the 12 phases of the cardiac cycle, and changes in aqueduct size during the cardiac cycle were determined. The SV was calculated using 12 different aqueductal ROIs and compared with the SV calculated using a fixed ROI size. RESULTS: There was variation in the size of the aqueduct during the cardiac cycle. In addition, the measured SV increased with a greater area of the ROI. A significant difference in the calculated SVs with the 12 variable ROIs was observed compared with that using a fixed ROI throughout the cardiac cycle. CONCLUSION: To establish reliable reference values for the SV in future studies, a variable ROI should be considered.

Quantitative assessment of cerebrospinal fluid flow and volume in enlargement of the subarachnoid spaces of infancy using MRI.

BACKGROUND: The etiology of enlarged subarachnoid spaces of infancy is unknown; however, there is radiologic similarity with normal pressure hydrocephalus. Adults with normal pressure hydrocephalus have been shown to have altered cerebrospinal (CSF) flow through the cerebral aqueduct. OBJECTIVE: To explore potential similarity between enlarged subarachnoid spaces of infancy and normal pressure hydrocephalus, we compared MRI-measured CSF flow through the cerebral aqueduct in infants with enlarged subarachnoid spaces of infancy to infants with normal brain MRIs. MATERIALS AND METHODS: This was an IRB approved retrospective study. Clinical brain MRI examinations including axial T2 imaging and phase contrast through the aqueduct were reviewed for infants with enlarged subarachnoid spaces of infancy and for infants with a qualitatively normal brain MRI. The brain and CSF volumes were segmented using a semi-automatic technique (Analyze 12.0) and CSF flow parameters were measured (cvi42, 5.14). All data was assessed for significant differences while controlling for age and sex using analysis of covariance (ANCOVA). RESULTS: Twenty-two patients with enlarged subarachnoid spaces (mean age 9.0 months, 19 males) and 15 patients with normal brain MRI (mean age 18.9 months, 8 females) were included. Volumes of the subarachnoid space (P < 0.001), lateral (P < 0.001), and third ventricles (P < 0.001) were significantly larger in infants with enlarged subarachnoid spaces of infancy. Aqueductal stroke volume significantly increased with age (P = 0.005), regardless of group. CONCLUSION: CSF volumes were significantly larger in infants with enlarged subarachnoid spaces of infancy versus infants with a normal MRI; however, there was no significant difference in CSF flow parameters between the two groups.

Neuronavigated endoscopic aqueductoplasty with panventricular stent plus septostomy for isolated fourth ventricle in complex hydrocephalus and syringomyelia associated with myelomeningocele: how I do it.

BACKGROUND: Isolated fourth ventricle (IFV) is a challenging entity to manage. In recent years, endoscopic treatment for aqueductoplasty has been on the rise. However, in patients with complex hydrocephalus and distorted ventricular system, its implementation can be complex. METHODS: We present a 3-year-old patient with myelomeningocele and postnatal hydrocephalus treated by ventriculoperitoneal shunt. In follow-up, a progressive IFV and isolated lateral ventricle with symptoms of the posterior fossa developed. An endoscopic aqueductoplasty (EA) with panventricular stent plus septostomy guided with neuronavigation was decided due to the complexity of the ventricular system. CONCLUSION: In IFV associated with complex hydrocephalus with distortion of the ventricular system, navigation can be of great help for planning and as a guide for performing EA.

Tetraventricular hydrocephalus with aqueductal flow void: an overlooked entity having consistent improvement following endoscopic third ventriculostomy.

BACKGROUND: Tetraventricular Hydrocephalus (TetHCP) is a heterogeneous group of cerebrospinal fluid (CSF) flow disorders having varying success rates with Endoscopic third ventriculostomy (ETV). This is report on the efficacy and rationale of ETV in a specific subset of primary TetHCP with aqueductal CSF flow voids. METHODS: Patients of primary acquired TetHCP presenting with increasing head size and/or headache having aqueductal CSF flow void on sagittal Magnetic Resonance Imaging (MRI) were included in this study. All of them underwent ETV. All patients were evaluated for clinical improvement & MRI at 3 months, and need for any additional procedure, in contrast to those without CSF flow void. The pathophysiology of hyperdynamic CSF circulation and its correlation to ETV was further reviewed. RESULTS: Eleven patients had tetraventricular hydrocephalus and aqueductal flow void, with age ranging from 10 months to 59 years. Two patients who could undergo quantitative flow study confirmed the hyperdynamic flow across the aqueduct. Following ETV, all showed clinical improvement. MRI at 3 months showed CSF flow void across the third ventricular stoma in addition to across the aqueduct. None of these patients required any redo procedures for a mean follow-up of 39.2 months. In contrast, there was 30% failure rate after ETV among 10 patients of tetraventricular hydrocephalus without aqueductal flow void. CONCLUSION: Tetraventricular hydrocephalus with aqueductal CSF flow void may be a unique entity with hyperdynamic CSF circulation and relative resistance at fourth ventricular outlets. ETV is highly efficacious in these patients, resulting in consistent clinico-radiological improvement.

A rare case of intralesional haemorrhage of a benign aqueductal cyst after CSF diversion treatment. A case report and review of literature.

Benign cysts within the pure aqueductal region are a rare entity. Their critical location within the ventricular system presents a risk of potentially catastrophic outcomes. We present a case of a 68-year-old female who was transferred to our unit with an acute obstructive triventricular hydrocephalus caused by a benign cyst within the cerebral aqueduct. She became unconscious and had an urgent endoscopic third ventriculostomy (ETV). Post-operatively, the patient was recovering well but then developed a sudden onset severe headache accompanied by vomiting. Imaging revealed intracystic haemorrhage with expansion of lesion but there was no obstructive hydrocephalus due to CSF diversion performed 9 d prior. She was treated conservatively and continued to improve.

Real-time imaging of respiratory effects on cerebrospinal fluid flow in small diameter passageways.

PURPOSE: Respiration-related CSF flow through the cerebral aqueduct may be useful for elucidating physiology and pathophysiology of the glymphatic system, which has been proposed as a mechanism of brain waste clearance. Therefore, we aimed to (1) develop a real-time (CSF) flow imaging method with high spatial and sufficient temporal resolution to capture respiratory effects, (2) validate the method in a phantom setup and numerical simulations, and (3) apply the method in vivo and quantify its repeatability and correlation with different respiratory conditions. METHODS: A golden-angle radial flow sequence (reconstructed temporal resolution 168 ms, spatial resolution 0.6 mm) was implemented on a 7T MRI scanner and reconstructed using compressed sensing. A phantom setup mimicked simultaneous cardiac and respiratory flow oscillations. The effect of temporal resolution and vessel diameter was investigated numerically. Healthy volunteers (n = 10) were scanned at four different respiratory conditions, including repeat scans. RESULTS: Phantom data show that the developed sequence accurately quantifies respiratory oscillations (ratio real-time/reference QR  = 0.96 ± 0.02), but underestimates the rapid cardiac oscillations (ratio QC  = 0.46 ± 0.14). Simulations suggest that QC can be improved by increasing temporal resolution. In vivo repeatability was moderate to very strong for cranial and caudal flow (intraclass correlation coefficient range: 0.55-0.99) and weak to strong for net flow (intraclass correlation coefficient range: 0.48-0.90). Net flow was influenced by respiratory condition (p < 0.01). CONCLUSIONS: The presented real-time flow MRI method can quantify respiratory-related variations of CSF flow in the cerebral aqueduct, but it underestimates rapid cardiac oscillations. In vivo, the method showed good repeatability and a relationship between flow and respiration.

A subject-specific assessment of measurement errors and their correction in cerebrospinal fluid velocity maps using 4D flow MRI.

PURPOSE: Phase-contrast MRI (PC-MRI) of cerebrospinal fluid (CSF) velocity is used to evaluate the characteristics of intracranial diseases, such as normal-pressure hydrocephalus (NPH). Nevertheless, PC-MRI has several potential error sources, with eddy-current-based phase offset error being non-negligible in CSF measurement. In this study, we assess the measurement error of CSF velocity maps obtained using 4D flow MRI and evaluate correction methods. METHODS: CSF velocity maps of 10 patients with NPH were acquired using 4D flow MRI (velocity-encoding = 5 cm/s). Distributed phase offset error was estimated for a whole 3D background field by polynomial fitting using robust regression analysis. This estimated phase offset error was then used to correct the CSF velocity maps. The estimated error profiles were compared with those obtained using an existing 2D correction approach involving local background information near the region of interest. RESULTS: The residual standard error of the polynomial fitting against the phase offset error extracted from the measured velocities was within 0.2 cm/s. The spatial dependencies of the phase offset errors showed similar tendencies in all cases, but sufficient differences in these values were found to indicate requirement of velocity correction. Differences of the estimated errors among other correction approaches were in the order of 10-2 cm/s, and the estimated errors were in good agreement with those obtained using existing approaches. CONCLUSION: Our method is capable of estimating the measurement error of CSF velocity maps obtained from 4D flow MRI and provides quantitatively reasonable characteristics for the main CSF profile in the cerebral aqueduct in patients with NPH.

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.

Endoscopic aqueductal membrane fenestration was effective for intractable hydrocephalus after removal of a nongerminomatous germ cell tumor exhibiting growing teratoma syndrome: a case report.

BACKGROUND: Primary central nervous system (CNS) germ cell tumors (GCTs) are rare neoplasms predominantly observed in the pediatric and young adult populations. A mixed GCT including immature teratoma exhibiting growing teratoma syndrome is presented. The pathogenesis of growing teratoma syndrome remains unclear, and its treatment strategy has not been established. GCTs are often located within the ventricles, causing hydrocephalus, which sometimes improves after removal of the tumor due to restoration of cerebrospinal fluid (CSF) flow. On the other hand, even if the flow route of CSF from the third ventricle to arachnoid granulations on the brain surface quadrigeminal cistern is restored after removal of the tumor, hydrocephalus may not improve. CASE PRESENTATION: A case whose intractable hydrocephalus improved after penetrating the aqueductal membrane via endoscopy is described. An 11-year-old boy was treated for pineal intracranial growing teratoma syndrome (IGTS). The tumor grew rapidly in a short period, and hydrocephalus progressed despite endoscopic third ventriculostomy (ETV). Although the obstruction was removed by radiation, chemotherapy, and total tumor resection, the hydrocephalus did not improve. Endoscopic membrane perforation was performed because a membrane-like structure was seen at the entrance of the cerebral aqueduct on magnetic resonance imaging. The hydrocephalus improved immediately after the operation, and the patient's consciousness disturbance also improved significantly. CONCLUSION: The purpose of this report is to update the current knowledge and standards of management for patients with growing teratoma syndrome, as well as to drive future translational and clinical studies by recognizing the unmet needs concerning hydrocephalus.