Impact of aquaporin-4 and CD11c + microglia in the development of ependymal cells in the aqueduct: inferences to hydrocephalus.

AQP4 is expressed in the endfeet membranes of subpial and perivascular astrocytes and in the ependymal cells that line the ventricular system. The sporadic appearance of obstructive congenital hydrocephalus (OCHC) has been observed in the offspring of AQP4-/- mice (KO) due to stenosis of Silvio's aqueduct. Here, we explore whether the lack of AQP4 expression leads to abnormal development of ependymal cells in the aqueduct of mice. We compared periaqueductal samples from wild-type and KO mice. The microarray-based transcriptome analysis reflected a large number of genes with differential expression (809). Gene sets (GS) associated with ependymal development, ciliary function and the immune system were specially modified qPCR confirmed reduced expression in the KO mice genes: (i) coding for transcription factors for ependymal differentiation (Rfx4 and FoxJ1), (ii) involved in the constitution of the central apparatus of the axoneme (Spag16 and Hydin), (iii) associated with ciliary assembly (Cfap43, Cfap69 and Ccdc170), and (iv) involved in intercellular junction complexes of the ependyma (Cdhr4). By contrast, genes such as Spp1, Gpnmb, Itgax, and Cd68, associated with a Cd11c-positive microglial population, were overexpressed in the KO mice. Electron microscopy and Immunofluorescence of vimentin and γ-tubulin revealed a disorganized ependyma in the KO mice, with changes in the intercellular complex union, unevenly orientated cilia, and variations in the planar cell polarity of the apical membrane. These structural alterations translate into reduced cilia beat frequency, which might alter cerebrospinal fluid movement. The presence of CD11c + microglia cells in the periaqueductal zone of mice during the first postnatal week is a novel finding. In AQP4-/- mice, these cells remain present around the aqueduct for an extended period, showing peak expression at P11. We propose that these cells play an important role in the normal development of the ependyma and that their overexpression in KO mice is crucial to reduce ependyma abnormalities that could otherwise contribute to the development of obstructive hydrocephalus.

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.

Aqueductal CSF stroke volume is associated with the burden of perivascular space enlargement in chronic adult hydrocephalus.

The inflow of CSF into perivascular spaces (PVS) in the brain is crucial for clearing waste molecules. Inefficiency in PVS flow leads to neurodegeneration. Failure of PVS flushing is associated with CSF flow impairment in the intracranial hydrodynamic condition of CSF hypo-pulsatility. However, enlarged PVS (ePVS), a finding indicative of PVS flow dysfunction, is also present in patients with derangement of CSF dynamics characterized by CSF hyper-pulsatility, which increases CSF flow. Intriguingly, two opposite intracranial hydrodynamic conditions would lead to the same result of impairing the PVS flushing. To investigate this issue, we assessed the subsistence of a dysfunctional interplay between CSF and PVS flows and, if the case, the mechanisms preventing a hyper-pulsatile brain from providing an effective PVS flushing. We analyzed the association between phase contrast MRI aqueductal CSF stroke volume (aqSV), a proxy of CSF pulsatility, and the burden of ePVS in chronic adult hydrocephalus, a disease involving a broad spectrum of intracranial hydrodynamics disturbances. In the 147 (85 males, 62 females) patients, the age at diagnosis ranged between 28 and 88 years (median 73 years). Ninety-seven patients had tri-ventriculomegaly and 50 tetra-ventriculomegaly. According to the extent of ePVS, 113 patients had a high ePVS burden, while 34 had a low ePVS burden. aqSV, which ranged between 0 and 562 µL (median 86 µL), was increased with respect to healthy subjects. Patients presenting with less ePVS burden had higher aqSV (p < 0.002, corrected for the multiple comparisons) than those with higher ePVS burden. The present study confirmed the association between CSF dynamics and PVS flow disturbances and demonstrated this association in intracranial hyper-pulsatility. Further studies should investigate the association between PVS flow failure and CSF hypo- and hyper-pulsatility as responsible/co-responsible for glymphatic failure in other neurodegenerative diseases, particularly in diseases in which CSF disturbances can be corrected, as in chronic adult hydrocephalus.

Third Ventricle Diameter Is Inversely Related to Thalamic Massa Intermedia Thickness in Hydrocephalus Caused by Congenital Aqueductal Stenosis.

BACKGROUND AND PURPOSE: In fetuses with lateral ventriculomegaly and normal posterior fossa cerebrospinal spaces, third ventricle distention is a compelling clue that supports a diagnosis of aqueductal stenosis. However, this association assumes normal ventricular anatomy. Structural constraints can impair pressure-induced compliance. We aimed to determine how thalamic massa intermedia size alterations may impact the size of the third ventricle in the setting of congenital aqueductal stenosis. MATERIALS AND METHODS: This retrospective study was performed at a single academic pediatric hospital after institutional review board approval. We searched our brain MRI reports for all examinations describing aqueductal stenosis and included all the patients who had both fetal and postnatal examinations. Patients with interhypothalamic adhesions and hydrocephalus unrelated to congenital aqueductal stenosis were excluded from this study. We evaluated all the MRIs for the presence of thalamic massa intermedia and documented third ventricle diameters (supraoptic recess, central and suprapineal recesses) and the thalamic massa intermedia circumference. The Spearman correlation was used to identify the potential relationship between the thalamic massa intermedia circumference and third ventricle size in fetal and postnatal MRIs. Patients were also stratified into 2 groups based on the presence or absence of thalamic massa intermedia. Mann-Whitney U tests were used to compare third ventricle diameters between these groups. RESULTS: The study included both fetal and postnatal studies from 59 patients. The overall third ventricle diameter was inversely proportional to the circumference of the thalamic massa intermedia in both groups (fetal: P = .001, ρ = -0.422; [95% CI, -0.628 to -0.181]; postnatal: P < .001, ρ = -0.653; [95% CI, -0.782 to -0.479]). Nonetheless, dilation of anterior and posterior recesses still occurred when the mid third ventricle was nondilated or less severely dilated in patients with an enlarged thalamic massa intermedia. Third ventricle dilation was most severe in patients lacking a thalamic massa intermedia compared with patients with a thalamic massa intermedia (P < .001). CONCLUSIONS: In patients with suspected congenital aqueductal stenosis, lack of marked third ventriculomegaly as conventionally measured can sometimes be explained by thickening of the thalamic massa intermedia. In this circumstance, it is important to evaluate the extreme recesses of the third ventricle for evidence of dilation on fetal MRI.

Validating the accuracy of real-time phase-contrast MRI and quantifying the effects of free breathing on cerebrospinal fluid dynamics.

BACKGROUND: Understanding of the cerebrospinal fluid (CSF) circulation is essential for physiological studies and clinical diagnosis. Real-time phase contrast sequences (RT-PC) can quantify beat-to-beat CSF flow signals. However, the detailed effects of free-breathing on CSF parameters are not fully understood. This study aims to validate RT-PC's accuracy by comparing it with the conventional phase-contrast sequence (CINE-PC) and quantify the effect of free-breathing on CSF parameters at the intracranial and extracranial levels using a time-domain multiparametric analysis method. METHODS: Thirty-six healthy participants underwent MRI in a 3T scanner for CSF oscillations quantification at the cervical spine (C2-C3) and Sylvian aqueduct, using CINE-PC and RT-PC. CINE-PC uses 32 velocity maps to represent dynamic CSF flow over an average cardiac cycle, while RT-PC continuously quantifies CSF flow over 45-seconds. Free-breathing signals were recorded from 25 participants. RT-PC signal was segmented into independent cardiac cycle flow curves (Qt) and reconstructed into an averaged Qt. To assess RT-PC's accuracy, parameters such as segmented area, flow amplitude, and stroke volume (SV) of the reconstructed Qt from RT-PC were compared with those derived from the averaged Qt generated by CINE-PC. The breathing signal was used to categorize the Qt into expiratory or inspiratory phases, enabling the reconstruction of two Qt for inspiration and expiration. The breathing effects on various CSF parameters can be quantified by comparing these two reconstructed Qt. RESULTS: RT-PC overestimated CSF area (82.7% at aqueduct, 11.5% at C2-C3) compared to CINE-PC. Stroke volumes for CINE-PC were 615 mm³ (aqueduct) and 43 mm³ (spinal), and 581 mm³ (aqueduct) and 46 mm³ (spinal) for RT-PC. During thoracic pressure increase, spinal CSF net flow, flow amplitude, SV, and cardiac period increased by 6.3%, 6.8%, 14%, and 6%, respectively. Breathing effects on net flow showed a significant phase difference compared to the other parameters. Aqueduct-CSF flows were more affected by breathing than spinal-CSF. CONCLUSIONS: RT-PC accurately quantifies CSF oscillations in real-time and eliminates the need for cardiac synchronization, enabling the quantification of the cardiac and breathing components of CSF flow. This study quantifies the impact of free-breathing on CSF parameters, offering valuable physiological references for understanding the effects of breathing on CSF dynamics.

Mother-Daughter Ventricular Endoscopy: A Technical Note and 2-Dimensional Video.

BACKGROUND AND IMPORTANCE: While navigating the ventricles with a rigid endoscope provides excellent visualization and the ability to use endoscopic instruments for complex surgery, these endoscopes are often too large to navigate tight areas. We present a surgical video showing the technique of mother-daughter endoscopy, which consists of the introduction of a flexible 1-mm fiberoptic endoscope through the channel of a large rigid endoscope to allow visualization across small spaces or channels, in this case, the cerebral aqueduct. This combination of superior visualization and handling of rigid endoscopes and flexibility and small size of fiberoptic endoscopes enhances safety and broadens possibilities in ventricular surgery. CLINICAL PRESENTATION: A 64-year-old woman with prior endoscopic aqueductoplasty for triventricular hydrocephalus and a failed endoscopic third ventriculostomy presented with focal restenosis of the aqueduct. A repeat endoscopic aqueductoplasty with stent placement were performed. Mother-daughter endoscopy was used to explore the occluded aqueduct for improved safety before fenestration and to ensure proper stent placement after fenestration. CONCLUSION: Mother-daughter endoscopy can add safety to complex or high-risk endoscopic procedures, particularly those with tight spaces that the large mother endoscope cannot visualize.

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.

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.

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.

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.

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.

Seismic response analysis of double-trough aqueduct considering fluid-structure interaction effect.

At present, the crude fluid-structure interaction analysis model cannot accurately characterize the interaction mechanism between aqueduct and water under earthquake action. In order to solve this problem, this paper analyzes the seismic response of the double-tank aqueduct under the action of earthquake by using the shaker test and the VOF (Volume of Fluid) method considering the free liquid level from the perspective of fluid-solid bidirectional coupling, explores whether the liquid movement in the double tank is consistent and the shock absorption effect of different water levels on the aqueduct, and analyzes the amplitude of free liquid level sloshing and the change of horizontal dynamic pressure caused by water level change from the generation mechanism of TLD (Liquid tuning dampers). The results show that the liquid movement in the two tanks in the double-channel aqueduct is basically the same under the action of earthquake, and the TLD effect of the liquid gradually increases with the increase of the water level in the aqueduct, and the maximum peak shock absorption rate is 63.4% at the maximum peak and 50.4% in numerical simulation. The shaking amplitude of the liquid is positively correlated with the water level height, and the magnitude of the shaking amplitude also reflects the magnitude of the moving water pressure.

The Extreme Anterior Interhemispheric Transcallosal Approach for Pure Aqueduct Tumors: An Anatomical Study.

AIM: To show the normal anatomy of the cerebral aqueduct, and the feasibility of the extreme anterior interhemispheric transcallosal approach to remove tumors within the aqueduct. MATERIAL AND METHODS: This human cadaveric brain research was composed of ten formalin-fixed human brains and one injected head. The dissection was performed under an operative microscope with 6x to 40x magnification. The cerebral aqueduct anatomy was delineated along with the relationship to nearby structures in the extreme anterior interhemispheric transcallosal approach. RESULTS: We described the anatomy of the cerebral aqueduct within the brain and showed that, with the proper angle for the extreme anterior interhemispheric transcallosal approach, lesions in the cerebral aqueduct can be reached in a single session without damaging periventricular structures. CONCLUSION: The extreme anterior interhemispheric transcallosal approach provides a direct corridor to the cerebral aqueduct and, thus, is feasible for resecting pure aqueduct tumors in an already dilated intraventricular foramen.

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.

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.

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.

Biomechanical effects of hyper-dynamic cerebrospinal fluid flow through the cerebral aqueduct in idiopathic normal pressure hydrocephalus patients.

Normal pressure hydrocephalus (NPH) is an intracranial disease characterized by an abnormal accumulation of cerebrospinal fluid (CSF) in brain ventricles within the normal range of intracranial pressure. Most NPH in aged patients is idiopathic (iNPH) and without any prior history of intracranial diseases. Although an abnormal increase of CSF stroke volume (hyper-dynamic CSF flow) in the aqueduct between the third and fourth ventricles has received much attention as a clinical evaluation index in iNPH patients, the biomechanical effects of this flow on iNPH pathophysiology are poorly understood. This study aimed to clarify the potential biomechanical effects of hyper-dynamic CSF flow through the aqueduct of iNPH patients using magnetic resonance imaging-based computational simulations. Ventricular geometries and CSF flow rates through aqueducts of 10 iNPH patients and 10 healthy control subjects were obtained from multimodal magnetic resonance images, and these CSF flow fields were simulated using computational fluid dynamics. As biomechanical factors, we evaluated wall shear stress on the ventricular wall and the extent of flow mixing, which potentially disturbs the CSF composition in each ventricle. The results showed that the relatively high CSF flow rate and large and irregular shapes of the aqueduct in iNPH resulted in large wall shear stresses localized in relatively narrow regions. Furthermore, the resulting CSF flow showed a stable cyclic motion in control subjects, whereas strong mixing during transport through the aqueduct was found in patients with iNPH. These findings provide further insights into the clinical and biomechanical correlates of NPH pathophysiology.

Spontaneous Third Ventriculostomy in Cases of Aqueductal Stenosis: A Retrospective Case Series.

BACKGROUND: Spontaneous third ventriculostomy (STV) is a rare occurrence in cases of obstructive hydrocephalus where the walls of the third ventricle rupture, communicating the ventricular system, and the subarachnoid space leading to arrest of active hydrocephalus. We aim to review our series of STVs while reviewing previous reports. METHODS: A retrospective review of cases undergoing cine phase-contrast magnetic resonance imaging (PC-MRI) from 2015 to 2022 of any age with imaging evidence of arrested obstructive hydrocephalus was performed. Patients in which aqueductal stenosis was radiologically evident and the presence of third ventriculostomy through which cerebrospinal fluid flow was detectable were included. Patients who previously underwent endoscopic third ventriculostomy were excluded. Data on patient demographics, presentation, and imaging details of STV and aqueductal stenosis were collected. We searched the PubMed database using the following keyword combination: ((("spontaneous ventriculostomy") OR ("spontaneous third ventriculostomy")) OR ("spontaneous ventriculocisternostomy")) including English reports of STV published between 2010 and 2022. RESULTS: Fourteen cases were included (7 adults, 7 pediatrics), all with history of hydrocephalus. STV occurred in the floor of the third ventricle in 57.1% of the cases, at the lamina terminalis in 35.7%, and at both sites in 1 case. Eleven publications reporting 38 cases of STV were identified from 2009 to date. Minimum follow-up period was 10 months and maximum follow-up is 77 months. CONCLUSIONS: In cases of chronic obstructive hydrocephalus, neurosurgeons should be minded with the possibility of the presence of an STV on cine phase-contrast magnetic resonance imaging leading to arrested hydrocephalus. The delayed flow at the aqueduct of Sylvius might not be the only determinant of the necessity of cerebrospinal fluid diversion and the presence of an STV should be factored into the neurosurgeon's decision considering the patient's clinical picture.