Ventricular System Research Articles

Normal pressure hydrocephalus in adult mice causes gait impairment, cognitive deficits, and urinary frequency with incontinence.

Normal pressure hydrocephalus (NPH) is marked by enlarged cerebral ventricles with normal intracranial pressure, plus three stereotypical symptoms: gait impairment, cognitive dysfunction, and urinary frequency with urge-incontinence. The neural circuit dysfunction responsible for each of these symptoms remains unknown, and an adult mouse model would expand opportunities to explore these mechanisms in preclinical experiments. Here, we describe the first mouse model of chronic, communicating hydrocephalus with normal intracranial pressure. Hydrocephalic male and female mice had unsteady gait and reduced maximum velocity. Despite performing well on a variety of behavioral tests, they exhibited subtle learning impairments. Hydrocephalic mice also developed urinary frequency, and many became incontinent. This mouse model, with symptoms resembling human NPH, can be combined with molecular-genetic tools in any mouse strain to explore the neural circuit mechanisms of these symptoms. Preclinical work using this hydrocephalus model will lead to the development of new treatments for NPH symptoms.Significance Statement Like human patients with normal pressure hydrocephalus (NPH), mice with communicating hydrocephalus develop enlarged cerebral ventricles with normal intracranial pressure plus three stereotypical symptoms: gait impairment, cognitive dysfunction, and urinary frequency with incontinence. This mouse model, with symptoms resembling human NPH, can be combined with molecular-genetic tools in any mouse strain to explore neural circuit mechanisms of NPH symptoms.

Anatomical Characteristics of Cervicomedullary Compression on MRI Scans in Children with Achondroplasia

This retrospective study assessed anatomical characteristics of cervicomedullary compression in children with achondroplasia. Twelve anatomical parameters were analyzed (foramen magnum diameter and area; myelon area; clivus length; tentorium and occipital angles; brainstem volume outside the posterior fossa; and posterior fossa, cerebellum, supratentorial ventricular system, intracranial cerebrospinal fluid, and fourth ventricle volumes) from sagittal and transversal T1- and T2-weighted magnetic resonance imaging (MRI) scans from 37 children with achondroplasia aged ≤ 4 years (median [range] 0.8 [0.1–3.6] years) and compared with scans from 37 children without achondroplasia (median age 1.5 [0–3.9] years). Mann–Whitney U testing was used for between-group comparisons. Foramen magnum diameter and area were significantly smaller in children with achondroplasia compared with the reference group (mean 10.0 vs. 16.1 mm [p < 0.001] and 109.0 vs. 160.8 mm2 [p = 0.005], respectively). The tentorial angle was also steeper in children with achondroplasia (mean 47.6 vs. 38.1 degrees; p < 0.001), while the clivus was significantly shorter (mean 23.5 vs. 30.3 mm; p < 0.001). Significant differences were also observed in myelon area, occipital angle, fourth ventricle, intracranial cerebrospinal fluid and supratentorial ventricular volumes, and the volume of brainstem protruding beyond the posterior fossa (all p < 0.05). MRI analysis of brain structures may provide a standardized value to indicate decompression surgery in children with achondroplasia.

Frontal Horn of Lateral Ventricle of Brain and Its Relation with Age, Gender and Side: Morphometric Study by Computed Tomography among Bangladeshi Population

Background: Knowledge of the baseline reference value of frontal horn size is necessary for the initial and precise analysis of ventriculomegaly. The purpose of this study was to determine the size of frontal horn of lateral ventricle and its relation with age, gender and side among adult Bangladeshi population of Chattogram district. Materials and methods: This cross-sectional analytical study was conducted during the period from July 2022 to June 2023 in the Department of Anatomy, Chittagong Medical College, Chattogram, upon 150 respondents of 20-60 years who had normal Computed Tomography (CT) scans as reported by an expert radiologist. For statistical analysis, Mann-Whitney U test, Wilcoxon signed rank test and ANOVA test were done. p-value was considered significant if it was <0.05 at 95% level of confidence. Results: The mean right and left frontal horn length was 25.50 (±3.95) mm and 25.28 (±4.04) mm respectively. The length of the frontal horn of both right and left sided lateral ventricle were significantly higher in male than that of female (p<0.01). Spearman's correlation coefficient indicated positive linear correlation of length of frontal horn (Right and left side) with age, insignificant in right side (p=0.061) but significant in left side (p=0.046). Conclusion: Morphometric analysis of the frontal horn of the lateral ventricles among the Bangladeshi population produced a number of significant results that may help with the early diagnosis and treatment of neurological diseases that are particular to gender and age. These findings can be validated and expanded upon in future research using bigger sample sizes and cutting-edge imaging methods. IAHS Medical Journal Vol 7(1), June 2024; 54-59

EXTH-84. A DURABLE RECURRENT INTRACEREBROVENTRICULAR INFUSION METHOD IN MICE FOR PRECLINICAL ASSESSMENT OF CELLULAR THERAPEUTICS

Abstract BACKGROUND Significant advancement in cellular treatments for glioblastoma has been made in recent years. The administration route has shifted from intravenous access to local delivery, namely intracerebroventricular (ICV) delivery, in order to prevent the injected cellular products from becoming trapped in peripheral organs such as liver and spleen. There is currently no reliable preclinical system available to accurately examine new cellular treatments that involve long-term recurrent infusion into the cerebral ventricles. METHOD We optimized the surgical device and technique by modifying a commercially available ICV device with a predetermined needle length, eliminating the requirement for spacers hence relieving the tension of the surgical wounds. To avoid skin puncture, we substituted the tunneled catheter with a silicon catheter. The surgical incisions were secured with autoclips in replacement of sutures. We administered periodic infusions of engineered monocytes on a weekly basis using the tunneled catheter for a duration of 8 weeks. The rate of wound dehiscence was monitored. RESULTS The delivery of the engineered monocytes to the cerebral ventricle via the ICV device has been confirmed using a bioluminescence-based imaging. The device and the tunneled catheter demonstrate a long-lasting durability for a minimum of 8 weeks. The optimized device and method effectively reduce the occurrence of post-operative wound dehiscence. Using a silicon catheter minimizes skin punctures. CONCLUSION Our optimized ICV device, material, and surgical approach offer a dependable preclinical instrument for the long-term and recurrent delivery of cellular therapies that reflect patients’ clinical treatment schedules and provide a more accurate evaluation of their translational potential.

ANGI-01. EXTRANEURAL METASTATIC EPENDYMOMA: DISTANT METASTASIS TO THE PLEURA, LUNGS, LYMPH NODES, AND BONE

Abstract Ependymomas are neuroepithelial tumors arising from ependymal cells surrounding the cerebral ventricles that account for 1.6-1.8% of primary CNS tumors. They rarely metastasize to extraneural structures, with one study reporting an incidence of 6.2% with a mean time from diagnosis to extraneural metastasis of 75.6 months. This spread, when it does occur, has been reported to occur to the lungs, lymph nodes, liver, and bone. We describe the case of a patient with recurrent WHO Grade III ependymoma, ZFTA::RELA fusion positive, with extraneural metastatic disease to the thoracic spine, lungs, and pelvic bones. He was treated with multiple surgical resections, radiation therapy, and salvage chemotherapy for his extraneural metastasis to the lungs, bone, pleural space, and lymph nodes. His functional and respiratory statuses declined until he ultimately developed pneumonia, status epilepticus, then spontaneous respiratory arrest, which resulted in his passing away. Salvage chemotherapy for ependymoma has unclear mortality benefit and more research must be done to determine how best to treat patients with extraneural metastases, particularly those who fail traditional treatment with resection and radiation therapy.

TMOD-07. DEVELOPMENT AND CHARACTERIZATION OF A SPINAL CORD DIFFUSE MIDLINE GLIOMA MODEL

Abstract Diffuse midline gliomas (DMGs) are very aggressive central nervous system tumors that occur mainly in children and adolescents. Most DMGs develop in the brainstem, but they can also be found in the thalamus and the spinal cord, the latter comprising 4% of all DMGs. Despite advances in current treatments, the outcome for DMG patients remains extremely poor. The success of immunotherapy in other tumors encourages its translation to DMGs, for which the understanding of the tumor immune microenvironment (TIME) is imperative. The field counts with several murine DMG models in the pontine and thalamic locations. However, there is a paucity of spinal cord models. Thus, in this work, we have generated an orthotopic syngeneic model of H3K27M spinal cord DMG by injecting the tumor cells directly into the spinal cord under the T2 vertebra. We monitored tumor growth by bioluminescence and PET using 18F-FDG and 11C-methionine. As the tumor grew, we observed human-like symptoms in the mice, such as hemiplegia and hemiparesis. TIME characterization showed that this tumor model is mainly infiltrated by macrophages and almost devoid of lymphocytes. We are currently delving into the phenotype of these populations by scRNAseq and spatial transcriptomics. In addition, we are comparing our findings with human samples (n=15) to assess whether our model mimics human disease and can serve as a bonafide model of this tumor location. As a proof of concept, treatment of spinal DMG-bearing mice with a TIM-3 antagonist antibody, previously described as effective in pontine DMG-bearing mice, increased the median overall survival. We showed by microPET imaging that anti-TIM-3 administration into the brain ventricles diffuses to the tumor. These results open a path for the characterization of the spinal cord DMG TIME and for testing preclinical treatments in this new model.

CNSC-32. CHARACTERISTIC ANALYSIS OF SPREAD AND METASTASIS OF HIGH-GRADE GLIOMA

Abstract OBJECT Exploring the clinical characteristics of spread and metastasis of high-grade glioma is helpful for clinicians to further understand high-grade glioma, optimize clinical decision-making, and make treatment plans. METHOD Clinical data of patients diagnosed with WHO Grade 4 glioma with spread and metastasis in the course of disease in Guangdong Sanjiu Brain Hospital from January 1, 2017 to December 31, 2020 were collected and analyzed. RESULTS 93 patients were included in the analysis, 59 males and 34 females, median age of 42 years (3-71 years). Tumors were located supratentorial in 78 patients (83.9%). Most patients (70, 75.3%) had tumors adjacent to the ventricular system. 28 patients (30.1%) had tumor spread at first diagnosis. All patients received surgical at first diagnosis, including total resection in 36 cases (38.7%), partial resection in 42 cases (45.2%), and biopsy in 15 cases (16.1%). In 48 patients (51.6%), ventricles were opened during operation. 69 cases (74.2%) were pathologically diagnosed with glioblastoma, 81 cases (92.0%) were IDH wild-type. MRI findings of dissemination were linear in 50.0% (46 cases), nodular type in 25.0% (23 cases), mixed type in 25.0% (23 cases), and the remaining 1 case was undetermined. Cerebrospinal fluid examination was performed in 37 cases, which 11 cases were cytological positive (29.7%). Median OS for patients with initial dissemination was 338 days. Of the 68 patients developed transmission after treatment, median OS fro initial diagnosis to transmission was 254 days, the overall median OS was 409 days. The overall median OS for all patients was 403 days. The median OS of newly diagnosed patients with tumor spread was lower than that of patients with tumor spread after treatment, but there was no statistical difference (p=0.05). CONCLUSION Most high-grade glioma patients develop tumor spread within 1 year, and these patients have unique clinical characteristics. The positive rate of cerebrospinal fluid tumor cells is low, MRI imaging is still the main diagnostic option.

Non-secreting IL12 expressing oncolytic adenovirus Ad-TD-nsIL12 in recurrent high-grade glioma: a phase I trial

Malignant glioma is a highly fatal central nervous system malignancy with high recurrence rates. Oncolytic viruses offer potential treatment but need improvement in efficacy and safety. Here we describe a phase I, dose-escalating, single arm trial (ChiCTR2000032402) to study the safety of Ad-TD-nsIL12, an oncolytic adenovirus expressing non-secreting interleukin-12, in patients with recurrent high-grade glioma that connects with the ventricular system. Eight patients received intratumoral treatment via stereotaxis or an Ommaya reservoir, with doses ranging from 5 × 109 to 5 × 1010vp. The primary end point was to determine the maximal tolerated dose. Secondary endpoints included toxicity and anti-tumour ability. Minimal adverse events were observed at doses of 5 × 109 and 1 × 1010vp. Grade 3 seizure was observed in two patients from Cohort 3 (5 × 1010vp). Therefore, the maximum tolerated dose was determined to be 1 × 1010vp. Four patients developed hydrocephalus during follow-up. Among them, symptoms in two patients were relieved after placement of a ventriculo-peritoneal shunt, and the other two only showed ventriculomegaly on MRI scan without neurological deterioration. Complete response (according to Response Assessment in Neuro-Oncology Criteria) in one patient, a partial response in one patient and post-treatment infiltrations of CD4+ and CD8 + T cells into the tumour were documented during this trial. In conclusion, Ad-TD-nsIL12 has demonstrated safety and preliminary efficacy in patients with recurrent high-grade glioma.

Comprehensive Morphometric Analysis to Identify Key Neuroimaging Biomarkers for the Diagnosis of Adult Hydrocephalus Using Artificial Intelligence.

Hydrocephalus involves abnormal cerebrospinal fluid accumulation in brain ventricles. Early and accurate diagnosis is crucial for timely intervention and preventing progressive neurological deterioration. The aim of this study was to identify key neuroimaging biomarkers for the diagnosis of hydrocephalus using artificial intelligence to develop practical and accurate diagnostic tools for neurosurgeons. Fifteen 1-dimensional (1-D) neuroimaging parameters and ventricular volume of adult patients with non-normal pressure hydrocephalus and healthy subjects were measured using manual image processing, and 10 morphometric indices were also calculated. The data set was analyzed using 8 machine, ensemble, and deep learning classifiers to predict hydrocephalus. SHapley Additive exPlanations (SHAP) feature importance analysis identified key neuroimaging diagnostic biomarkers. Gradient Boosting achieved the highest performance, with an accuracy of 0.94 and an area under the curve of 0.97. SHAP analysis identified ventricular volume as the most important parameter. Given the challenges of measuring volume for clinicians, we identified key 1-D morphometric biomarkers that are easily measurable yet provide similar classifier performance. The results showed that the frontal-temporal horn ratio, modified Evan index, modified cella media index, sagittal maximum lateral ventricle height, and coronal posterior callosal angle are key 1-D diagnostic biomarkers. Notably, higher modified Evan index, modified cella media index, and sagittal maximum lateral ventricle height, and lower frontal-temporal horn ratio and coronal posterior callosal angle values were associated with hydrocephalus prediction. The results also elucidated the relationships between these key 1-D morphometric parameters and ventricular volume, providing potential diagnostic insights. This study highlights the importance of a multifaceted diagnostic approach incorporating 5 easily measurable 1-D neuroimaging biomarkers for neurosurgeons to differentiate non-normal pressure hydrocephalus from healthy subjects. Incorporating our artificial intelligence model, interpreted through SHAP analysis, into routine clinical workflows may transform the diagnostic landscape for hydrocephalus by standardizing diagnosis and overcoming the limitations of visual evaluations, particularly in early stages and challenging cases.

Choroid plexus as a mediator of CNS inflammation in multiple sclerosis.

The pathophysiology of multiple sclerosis (MS) remains poorly understood despite decades of tremendous research efforts. Advances in neuroradiography coupled with availability of unbiased approaches including spatial transcriptomics, proteomics, metabolomics, and lipidomics that are compatible with brain and fluid specimens from patients raise hope that discovery of novel disease drivers is on the horizon. Once thought to be little more than salty bathwater, our modern understanding of cerebrospinal fluid (CSF) suggests the CSF as a compelling, critical regulator of brain function in health and disease. Recent studies in the field have reinvigorated interest in CSF as a medium to better understand MS and to deliver disease-modifying therapies. In turn, the choroid plexus, an epithelial tissue located within each brain ventricle that regulates CSF and forms a key blood-CSF barrier, is uniquely positioned to orchestrate neuroinflammation associated with MS. In this perspective review, we will discuss what is known about the choroid plexus as a conductor of immune responses and how it may propagate neuroinflammation associated with MS via the CSF.

TMEM106B amyloid filaments in the Biondi bodies of ependymal cells

Biondi bodies are filamentous amyloid inclusions of unknown composition in ependymal cells of the choroid plexuses, ependymal cells lining cerebral ventricles and ependymal cells of the central canal of the spinal cord. Their formation is age-dependent and they are commonly associated with a variety of neurodegenerative conditions, including Alzheimer’s disease and Lewy body disorders. Here, we show that Biondi bodies are strongly immunoreactive with TMEM239, an antibody specific for inclusions of transmembrane protein 106B (TMEM106B). Biondi bodies were labelled by both this antibody and the amyloid dye pFTAA. Many Biondi bodies were also labelled for TMEM106B and the lysosomal markers Hexosaminidase A and Cathepsin D. By transmission immuno-electron microscopy, Biondi bodies of choroid plexuses were decorated by TMEM239 and were associated with structures that resembled residual bodies or secondary lysosomes. By electron cryo-microscopy, TMEM106B filaments from Biondi bodies of choroid plexuses were similar (Biondi variant), but not identical, to the fold I that was previously identified in filaments from brain parenchyma.

ГЕМОДИНАМИКА ГОЛОВНОГО МОЗГА У НОВОРОЖДЕННЫХ ОТ МАТЕРЕЙ С ФЕТОПЛАЦЕНТАРНОЙ НЕДОСТАТОЧНОСТЬЮ

Objective. To determine the state of brain structures and blood flow parameters in the ventricular system in newborns whose mothers suffered from placental insufficiency using neurosonography and Doppler ultrasound. Material and methods. The study involved 96 newborns from mothers with placental insufficiency (the main group) and 30 healthy newborns (the control group). The diagnostic tools included a neurosonographic assessment of the anterior and middle cranial fossae, as well as Doppler ultrasound of the anterior and middle cerebral arteries, vein of Galen blood flow velocity assessment, systolic/diastolic ratio (S/D), resistive index (Ri) and pulsatility index (PI). Results. The comparative analysis of blood flow in the anterior cerebral artery and the vein of Galen did not reveal statistically significant differences between the main and control groups. While examining the middle cerebral artery, despite the absence of statistically significant differences in blood flow velocities compared with the control group, resistive index (Ri), pulsatility index (Pi) and systolic/diastolic ratio (S/D) showed statistically significant differences. This indicates increased vascular resistance in newborns from the main group. Conclusion. It is essential to combine Doppler ultrasound and neurosonography in order to make an objective assessment of the state of the newborns central nervous system from mothers with placental insufficiency. The study revealed impairment of hemodynamics in the middle cerebral arteries pool in newborns from the main group. To assess cerebral hemodynamics, it is preferable to use the Ri, Pi and S/D indices.

Current Trends in the Treatment of Pediatric Hydrocephalus: A Narrative Review Centered on the Indications, Safety, Efficacy, and Long-Term Outcomes of Available Treatment Modalities

The pathophysiologic substrate of pediatric hydrocephalus has not been thoroughly elucidated. Valve-based shunt systems have constituted the main therapeutic option since the late 1950s. The initially used systems were concerning the ventricular system and the atrium. In the 1970s, VA shunts were not the main stay of treatment as the preferred option for the terminal end of the drainage system was the peritoneum. Our review analyzes these valve types and attempts a comparison, based on their functional characteristics. Nowadays, the only available surgical alternative for the treatment of hydrocephalus is ETV. This technique is associated with lower infection rates as well as, on average, a lower re-operation rate. Another term that deserves special mention is related to the outcome of ETV in children who had a medical history of previously incorporated shunts and who were subsequently suffering from shunt malfunction. Well-recognized predictive factors associated with secondary ETV failure include age, early onset of hydrocephalus, and prematurity. Although several attempts have been made in order to establish the optimum surgical treatment management in the different subgroups of patientswho are suffering from shunt dysfunction, there is no universal agreement. Therefore, this review attempts to identify the specific subpopulations of patients in whom the insertion of a drainage system as the preferred treatment modality is associated with an optimum long-term prognosis, compared to ETV, and vice versa. The objective of our study is to analyze the safety, efficacy, and outcomes of drainage devices and ETV in pediatric hydrocephalus patients.

Ependymal cell lineage reprogramming as a potential therapeutic intervention for hydrocephalus.

Hydrocephalus is a common neurological condition, characterized by the excessive accumulation of cerebrospinal fluid in the cerebral ventricles. Primary treatments for hydrocephalus mainly involve neurosurgical cerebrospinal fluid diversion, which hold high morbidity and failure rates, highlighting the necessity for the discovery of novel therapeutic approaches. Although the pathophysiology of hydrocephalus is highly multifactorial, impaired function of the brain ependymal cells plays a fundamental role in hydrocephalus. Here we show that GemC1 and McIdas, key regulators of multiciliated ependymal cell fate determination, induce direct cellular reprogramming towards ependyma. Our study reveals that ectopic expression of GemC1 and McIdas reprograms cortical astrocytes and programs mouse embryonic stem cells into ependyma. McIdas is sufficient to establish functional activity in the reprogrammed astrocytes. Furthermore, we show that McIdas' expression promotes ependymal cell regeneration in two different postnatal hydrocephalus mouse models: an intracranial hemorrhage and a genetic form of hydrocephalus and ameliorates the cytoarchitecture of the neurogenic niche. Our study provides evidence on the restoration of ependyma in animal models mimicking hydrocephalus that could be exploited towards future therapeutic interventions.

Traditional dual-chamber right ventricular pacing versus conduction system pacing in the US medicare population

Abstract Introduction Conduction system pacing (CSP) has emerged as an alternative therapy to traditional right ventricular (RV) pacing. However, the majority of CSP studies reflect small cohorts or single-center experience. Purpose This analysis aimed to compare CSP to dual chamber (DC) RV pacing in a large, population-based cohort utilizing data from the Micra Coverage with Evidence Development (CED) study. Methods Medicare administrative claims data were used to identify patients implanted with a DC RV pacemaker. Lead placement data from Medtronic’s device registration system was used to identify patients with treated with CSP (N=6,197) using a 3830 catheter-delivered lead or DC RV (non-3830 lead, non-CSP placement) (N=16,989) at the same centers. CSP patients were stratified into left bundle branch area pacing (LBBAP) (N=4,738) and His-bundle pacing (HBP) (N=1,459). Incident heart failure hospitalizations (iHFH), all-cause mortality, complication rates and reinterventions at 6 months were analyzed. Results CSP (LBBAP and HBP) patients with a 3830 catheter-delivered lead experienced significantly lower rates of iHFH (HR: 0.70, P=0.02) and all-cause mortality at 6 months compared with DC RV patients (HR: 0.66, P<.0001) (figure). There was no difference in complications (HR: 0.89, P=0.06) or need for reintervention (HR: 0.83, P=0.08) with LBBAP compared to DC RV, though HBP patients experienced significantly higher rates of complications (HR: 1.41, P=0.001) compared to LBBAP. Conclusion Patients treated with CSP with a 3830 catheter-delivered lead experienced significant all-cause mortality and HFH benefits compared to DC RV pacing. LBBAP had lower complications compared to HBP. These real-world results in a large cohort of Medicare patients align with findings in small clinical studies demonstrating the benefits of LBBAP. Future research will focus on understanding patient selection for CSP.Figure

LA reservoir strain predicts elevated left atrial pressure in patients with Veno-Arterial (VA) extracorporeal membrane oxygenator (ECMO) support for cardiogenic shock

Abstract Background Veno-arterial (VA) extracorporeal membrane oxygenator (ECMO) is not a left ventricular (LV) support system as it increases aortic pressure and LV afterload due to retrograde blood flow in the aorta. This can lead to complications such as increased LV volume (LV distention), increased LV and left atrial (LA) pressures, and pulmonary edema. We sought to investigate the correlation between LA strain and invasive LA pressure (LAP) in patients with ECMO support for cardiogenic shock undergoing atrial septostomy with stenting. Methods and Results A total of 24 consecutive patients (52±20 years; 83% were male) undergoing atrial septostomy with stenting while being on ECMO support for cardiogenic shock for left heart decompression were analyzed. LAP was measured immediately after transeptal puncture and before deployment of interatrial septal stent. A comprehensive echocardiogram was performed in all patients prior to atrial septostomy. Median time difference between echocardiogram and LAP measurement was 3.5 (0.5-20) hours. LA strain analysis was performed using the TomTec Arena 2D-cardiac performance analysis (CPA) software. LA reservoir strain was measured at peak systole during the reservoir phase in a single apical 4-chamber view. Intraclass correlation coefficients between 2 different investigators were excellent (All> 0.95). Median LA reservoir strain and LAP were 3.2 (0.5-1) % and 23 (8-53) mmHg, respectively. LA reservoir strain significantly correlated with LAP (r=0.53, p=0.034). LA reservoir strain of < 1.5% can effectively predict markedly elevated LAP (LA> 30 mmHg) (OR =9.9, p =0.0016). Conclusions LA reservoir strain significantly correlated with invasive LAP. With the advent of strain imaging software, LA reservoir strain is a feasible, reproducible, noninvasive, and straightforward method to predict the need for left heart decompression and/or to guide optimal afterload management in patients with VA-ECMO for cardiogenic shock. Further a prospective simultaneous echocardiographic and invasive LAP study is needed.

ENDOSCOPIC THIRD VENTRICULOSTOMY VS VENTRICULOPERITONEAL SHUNT IN OBSTRUCTIVE HYDROCEPHALUS IN TERMS OF POST-OPERATIVE COMPLICATIONS

: Obstructive Hydrocephalus is a condition characterized by increased cerebrospinal fluid (CSF) volume within the brain's ventricular system, leading to clinical deterioration and disability. Without treatment, it can be fatal. Two primary treatment modalities are Ventriculoperitoneal Shunting (VPS) and Endoscopic Third Ventriculostomy (ETV), with ongoing debate over the superiority of one approach over the other. Objective: To compare the complications associated with Ventriculoperitoneal Shunting (VPS) and Endoscopic Third Ventriculostomy (ETV) in patients with obstructive hydrocephalus. Methods: A randomized controlled trial was conducted at a tertiary care hospital from April 15, 2024, to September 15, 2024. A total of 100 patients diagnosed with obstructive hydrocephalus were randomly allocated into two groups: 50 patients received VPS treatment, and 50 received ETV. Complications, including surgical site infection, seizures, hematoma, and CSF leakage, were recorded and analyzed. Results: Complications were observed in 36% (n=18) of patients in the VPS group compared to 16% (n=8) in the ETV group, with a statistically significant difference (p=0.023). Surgical site infections occurred in 8% (n=4) of VPS patients, while no infections were reported in the ETV group. Seizures were significantly more common in the VPS group, affecting 26% (n=13) compared to 8% (n=4) in the ETV group (p=0.017). Hematoma formation was observed in 4% (n=2) of VPS patients and 6% (n=3) of ETV patients. CSF leakage occurred in 4% (n=2) of VPS patients and 2% (n=1) of ETV patients. Conclusion: Endoscopic Third Ventriculostomy (ETV) demonstrated a significantly lower complication rate compared to Ventriculoperitoneal Shunting (VPS) in the management of obstructive hydrocephalus. These findings support ETV as a safer alternative with fewer associated complications.

Defects in exosome biogenesis are associated with sensorimotor defects in zebrafish vps4a mutants.

Mutations in human VPS4A are associated with neurodevelopmental defects, including motor delays and defective muscle tone. VPS4A encodes a AAA-ATPase required for membrane scission, but how mutations in VPS4A lead to impaired control of motor function is not known. Here we identified a mutation in zebrafish vps4a, T248I, that affects sensorimotor transformation. Biochemical analyses indicate that the T248I mutation reduces the ATPase activity of Vps4a and disassembly of ESCRT filaments, which mediate membrane scission. Consistent with the role for Vps4a in exosome biogenesis, vps4aT248I larvae have enlarged endosomal compartments in the CNS and decreased numbers of circulating exosomes in brain ventricles. Resembling the central form of hypotonia in VPS4A patients, motor neurons and muscle cells are functional in mutant zebrafish. Both somatosensory and vestibular inputs robustly evoke tail and eye movements, respectively. In contrast, optomotor responses, vestibulospinal, and acoustic startle reflexes are absent or strongly impaired in vps4aT248I larvae, indicating a greater sensitivity of these circuits to the T248I mutation. ERG recordings revealed intensity-dependent deficits in the retina, and in vivo calcium imaging of the auditory pathway identified a moderate reduction in afferent neuron activity, partially accounting for the severe motor impairments in mutant larvae. Further investigation of central pathways in vps4aT248I mutants showed that activation of descending vestibulospinal and midbrain motor command neurons by sensory cues is strongly reduced. Our results suggest that defects in sensorimotor transformation underly the profound yet selective effects on motor reflexes resulting from the loss of membrane scission mediated by Vps4a.Significance Statement Here we present a T248I mutation in vps4a, which causes sensorimotor defects in zebrafish larvae. Vps4a plays a key role in membrane scission. Spanning biochemical to systems level analyses, our study indicates that a reduction in Vps4a enzymatic activity leads to abnormalities in membrane-scission dependent processes such as endosomal protein trafficking and exosome biogenesis, resulting in pronounced deficits in sensorimotor transformation of visual, auditory, and vestibular cues. We suggest that the mechanisms underlying this type of dysfunction in zebrafish may also contribute to the condition seen in human patients with de novo mutations in the human VPS4A orthologue.

Embryotomy for head last retention: A case report from Thiès, Senegal

Introduction: Hydrocephalus is a pathology of heterogeneous nature and complex pathogenesis. It corresponds to an active distension of the ventricular system. Faced with hydrocephalus with retained head in a dead child, embryotomy by craniotomy is indicated. Case Report: We report a case of intrapartum fetal death with head-last retention due to hydrocephalus treated with craniotomy performed at the regional hospital of Thiès (CHRT). This was a 21-year-old primigravida patient seen for premature delivery in a pregnancy of 33 weeks 5 days. The ultrasound concluded that the pregnancy had stopped at 33 weeks 5 days with major hydrocephalus. A craniotomy followed by gradual evacuation of the cerebrospinal fluid allowed easy delivery of a fresh stillborn weighing 1950 grams. The afterbirth was simple. Conclusion: Embryotomy by craniotomy constitutes a good option to complete delivery by natural means in the face of head retention due to hydrocephalus with intrapartum death. It is therefore necessary to master this simple and less morbid technique than a cesarean section in such a situation.

Good Correlation between CT-Measured Z-Evans’ Index and CT Volumetric of Ventricular System in Patients with iNPH Treated by Cerebrospinal Fluid Shunting

Background: Patients with idiopathic normal pressure hydrocephalus (iNPH) demonstrated an increase in the volume of lateral ventricles oriented along the Z-axial axis, as opposed to the X-axial axis. Objective: To determine which computed tomography (CT)-measured X-Evans’ index and Z-Evans’ index, exhibit a stronger correlation with CT-derived ventricular volume both before and after shunting procedures. Additionally, a comparative examination between those with iNPH characterized by disproportionate enlargement of subarachnoid space hydrocephalus (DESH) and those without DESH features. Materials and Methods: The present study enrolled forty-three iNPH patients who underwent shunting between April 2013 and April 2016. The initial screening involved a thorough review of pre-shunting CT images, leading to the categorization of patients into two distinct groups, those with DESH and without DESH features. Results: Both the X-Evans’ index and Z-Evans’ index exhibited a noteworthy correlation with ventricular volume, substantiated by correlation coefficients (r) of 0.777 (p<0.001) and 0.876 (p<0.001), respectively. Notably, the correlation between the change in CT ventricular volume and the change in Z-Evans’ index was more conspicuous in the overall patient cohort (r=0.730, p<0.001) than X-Evans’ index change (r=0.599, p<0.001). This tendency was particularly discernible within the DESH group, where the correlation with Z-Evans’ index (r=0.826, p<0.001). Conclusion: The Z-Evans’ index emerged as a more effective representation of ventricular volume compared to the X-Evans’ index in the entirety of the iNPH patient cohort. In contrast, during the subsequent CT follow-up, the change in X-Evans’ index exhibited superior efficacy in capturing the corresponding alterations in ventricular volume.