Deep brain stimulation for essential tremor in patients with ventriculomegaly.

Background: Deep brain stimulation of the nucleus ventralis intermedius (VIM-DBS) is considered a safe and effective treatment for medically intractable essential tremor (ET). However, ventriculomegaly can provide a surgical challenge, as there is an increased risk of breaching the ventricle during the procedure, with potential risk of intraventricular hemorrhage and target displacement. Case Description: In this case series, we report successful bilateral VIM-DBS in a 72-year-old and 69-year-old female ET patient with significant ventriculomegaly. VIM-DBS therapy provided an excellent tremor response. After 5 years, a ventriculoperitoneal shunt was implanted in the first patient due to an incomplete Hakim-Adams triad, with significant improvement in gait and cognition. Conclusion: To the best of our knowledge, we present the first report on VIM-DBS in ET patients with ventriculomegaly and illustrate that VIM-DBS can provide an excellent tremor response in patients with medically intractable ET, even in the context of marked ventriculomegaly.

Atypical Presentation of Longstanding Overt Ventriculomegaly in Adults: A Case Report.

Hydrocephalus involves the enlargement of the ventricular system due to increased cerebrospinal fluid. This condition often presents with ventriculomegaly, associated with cognitive decline, gait disturbances, visual changes, and other neurological symptoms. In adults, hydrocephalus may result from longstanding overt ventriculomegaly in adults (LOVA), characterized by macrocephaly, subnormal IQ, urinary incontinence, and gait issues. In a recent case report, a 52-year-old Hispanic female displayed similar predisposing factors and radiological findings for a LOVA diagnosis. Despite the absence of focal neurological deficits or typical complaints, she experienced a breakthrough seizure episode after years without incident.

Prenatal and Postnatal Diagnosis and Genetic Background of Corpus Callosum Malformations and Neonatal Follow-Up.

INTRODUCTION: The corpus callosum is one of the five main cerebral commissures. It is key to combining sensory and motor functions. Its structure can be pathological (dysgenesis) or completely absent (agenesis). The corpus callosum dys- or agenesis is a rare disease (1:4000 live births), but it can have serious mental effects. METHODS: In our study, we processed the data of 64 pregnant women. They attended a prenatal diagnostic center and genetic counseling from 2005 to 2019 at the Department of Obstetrics and Gynecology at Semmelweis University. RESULTS: The pregnancies had the following outcomes: 52 ended in delivery, 1 in spontaneous abortion, and 11 in termination of pregnancy (TOP) cases (n = 64). The average time of detection with imaging tests was 25.24 gestational weeks. In 16 cases, prenatal magnetic resonance imaging (MRI) was performed. If the abnormality was detected before the 20th week, a genetic test was performed on an amniotic fluid sample obtained from a genetic amniocentesis. Karyotyping and cytogenetic tests were performed in 15 of the investigated cases. Karyotyping gave normal results in three cases (46,XX or XY). In one of these cases, postnatally chromosomal microarray (CMA) was later performed, which confirmed Aicardi syndrome (3q21.3-21.1 microdeletion). In one case, postnatally, the test found Wiedemann-Rautenstrauch syndrome. In other cases, it found X ring, Di George syndrome, 46,XY,del(13q)(q13q22) and 46,XX,del(5p)(p13) (Cri-du-chat syndrome). Edwards syndrome was diagnosed in six cases, and Patau syndrome in one case. CONCLUSIONS: We found that corpus callosum abnormalities are often linked to chromosomal problems. We recommend that a cytogenetic test be performed in all cases to rule out inherited diseases. Also, the long-term outcome does not just depend on the disease's severity and the associated other conditions, and hence proper follow-up and early development are also key. For this reason, close teamwork between neonatology, developmental neurology, and pediatric surgery is vital.

North American Fetal Therapy Network: Maternal Outcomes in Fetal Aqueductal Stenosis.

INTRODUCTION: Fetal aqueductal stenosis (AS) affects approximately 1:1,000 pregnancies. Obstruction of cerebral spinal fluid circulation occurs at the aqueduct of Sylvius, leading to progressive hydrocephalus and macrocephaly, which often necessitates cesarean section (CS). The purpose of this study was to describe maternal outcomes associated with fetal AS. METHODS: This study is conducted through the North American Fetal Therapy Network (NAFTNet). Subjects with a prenatal diagnosis of severe fetal central nervous system ventriculomegaly were recruited and followed longitudinally. Maternal events around the delivery of fetuses with AS were recorded and analyzed. RESULTS: Thirty-seven subjects with fetal AS confirmed by neonatal neuroimaging were analyzed. The average gestational age at delivery was 36.7 weeks. Overall, 86% were delivered by CS, and 62% of these were elective. Ninety-one percent of CSs were performed through a Pfannenstiel abdominal incision. A classical uterine incision was required in 13% of cesarean deliveries. The peripartum complication rate was 27%. CONCLUSION: Women carrying a fetus with AS were at risk for preterm birth, cesarean delivery, a classical uterine incision, and peripartum complications. These data highlight the maternal morbidity associated with fetal AS and the potential benefit of in utero therapy not only for neonatal outcomes but also for maternal outcomes.

Refining the phenotype of SINO syndrome: A comprehensive cohort report of 14 novel cases.

BACKGROUND: SINO syndrome (Spastic paraplegia, Intellectual disability, Nystagmus and Obesity) is a rare autosomal dominant condition caused by heterozygous variants in KIDINS220. A total of 12 individuals are reported, comprising eight with SINO and four with an autosomal recessive condition attributed to bi-allelic KIDINS220 variants. METHODS: In our international cohort, we have comprised 14 individuals, carrying 13 novel pathogenic KIDINS220 variants in heterozygous form. We assessed clinical and molecular data of our cohort and previously reported individuals and based on functional experiments reached a better understanding of the pathogenesis behind KIDINS220-related disease. RESULTS: Using fetal tissue and in vitro assays, we demonstrate that the variants generate KIDINS220 truncated forms that mislocalize in punctate intracellular structures, with decreased levels of the full-length protein, suggesting a trans-dominant negative effect. 92% had their diagnosis within three years, with symptoms of developmental delay, spasticity, hypotonia, lack of eye contact and nystagmus. We identified a KIDINS220 variant associated with fetal hydrocephalus and show that 58% of examined individuals present brain ventricular dilatation. We extend the phenotypic spectrum of SINO syndrome to behavioral manifestations not previously highlighted. CONCLUSION: Our study provides further insights into the clinical spectrum, etiology and predicted functional impact of KIDINS220 variants.

Is choroid plexus growth altered in isolated ventriculomegaly on fetal neuro-ultrasound?

OBJECTIVES: Reveal developmental alterations in choroid plexus volume (CPV) among fetuses with isolated ventriculomegaly (VM) through neuro-ultrasound. METHODS: This prospective study aimed to assess the development of fetal CPV in normal fetuses and those with isolated VM through neuro-ultrasound. The fetuses of isolated VM were categorized into mild, moderate, and severe groups, and subsequently, the lateral ventricle evolution was monitored. The developmental alterations in CPV among fetuses with isolated VM were determined by comparing the CPV z-scores with those of normal fetuses. Receiver operating characteristics curve analysis was used to assess the predictive value of altered CPV in lateral ventricle evolution. RESULTS: A total of 218 normal fetuses and 114 isolated VM fetuses from 22 weeks to 35 weeks of gestation were included. The CPV decreased as the isolated VM was getting worse. Both fetuses with isolated moderate ventriculomegaly and those with isolated severe ventriculomegaly exhibited reduced CPV compared to normal fetuses. The CPV in fetuses with isolated mild ventriculomegaly (IMVM) varied, with some showing a larger CPV compared to normal fetuses, while others exhibited a smaller CPV. The larger CPV in cases of IMVM may serve as a predictive factor for either regression or stability of the lateral ventricle, while reduced CPV in cases of isolated VM may indicate worsening of the lateral ventricle. CONCLUSION: The growth volume of fetal CP exhibited alterations in fetuses with isolated VM, and these changes were found to be correlated with the evolution of the lateral ventricle. CLINICAL RELEVANCE STATEMENT: Neuro-ultrasound revealed varying degrees of alterations in the volume development of the choroid plexus within the fetus with isolated VM. The findings can help predict lateral ventricle prognosis, greatly contributing to prenatal diagnosis strategies for fetuses with isolated VM. KEY POINTS: The volume of choroid plexus growth is altered in fetuses with isolated VM. The altered CPV in isolated VM was associated with lateral ventricle evolution. The findings are useful for prenatal counseling and managing fetuses with isolated VM.

Long-Standing Overt Ventriculomegaly in Adults (LOVA): Can You Blame Alcohol?

Long-standing overt ventriculomegaly in adults (LOVA) is a kind of chronic hydrocephalus that has been reported to have started in infancy and is characterized by severe ventriculomegaly and macrocephaly. It often manifests clinically in later adulthood. We describe the case of a 34-year-old male patient who had a history of chronic alcoholism and who had been complaining of headaches, disturbed gait, and frequent falls for three months when he arrived in a stupor at the emergency room. Massive ventriculomegaly with Evans' index of 0.40 was found during a head magnetic resonance imaging (MRI). The MRI results were more severe than the clinical manifestations. He was diagnosed with LOVA and treated with conservative hyperosmolar drugs, neuroprotective agents, and intravenous (IV) thiamine. The patient was discharged and consented to follow-up after a hospital stay of seven days.

Clinical characteristics and perinatal outcome of fetuses with ventriculomegaly.

PURPOSE: To assess the incidence of associated structural anomalies, chromosomal/genetic abnormalities, infections, and perinatal outcomes of fetuses with ventriculomegaly (VM), also to evaluate the role of fetal magnetic resonance imaging (MRI) in detecting associated intracranial anomalies. METHODS: Retrospective cohort study of 149 prenatally diagnosed pregnancies with fetal VM. VM was classified as mild (Vp = 10-12 mm), moderate (Vp = 12.1-15 mm), and severe (Vp > 15 mm). Fetal MRI was performed to 97 pregnancies. RESULTS: The incidences of an associated CNS, non-CNS, chromosomal anomaly, genetic abnormality and fetal infection were 42.3%, 11.4%, 6.1%, 2.1% and 1.3%, respectively. Fetal MRI identified additional CNS anomalies in 6.7% of cases, particularly in severe VM. The incidences of perinatal outcomes were 18.8% termination of pregnancy, 4% intrauterine and 8.1% neonatal or infant death. The rates of fetuses alive at > 12 months of age with neurological morbidity were 2.6%, 11.1% and 76.9% for mild, moderate and severe isolated VM, respectively. CONCLUSION: The prognosis of fetuses with VM mostly depends on the severity and the associated anomalies. Mild to moderate isolated VM generally have favorable outcomes. Fetal MRI is particularly valuable in fetuses with isolated severe VM.

Assessment of Ventricular Size and Neurocognitive Outcomes in Children with Postnatal Closure of Myelomeningocele.

OBJECTIVE: To assess if ventricular size before shunting is correlated with neurodevelopmental outcomes in children with postnatal myelomeningocele closure. STUDY DESIGN: This retrospective review included children with postnatal surgical closure of myelomeningocele and neuropsychological testing between 2018 and 2023 at the University of California, San Francisco. Frontal-occipital horn ratio (FOHR) was measured immediately before shunt placement or on the first study that reported ventricular stability for nonshunted patients. The primary outcome was full scale IQ (FSIQ) on the Weschler Intelligence Scale. Secondary outcomes included indices of the Weschler scale, the Global Executive Composite from the Behavior Rating Inventory of Executive Function, and the general adaptive composite from the Adaptive Behavior Assessment Scale. Univariable and multivariable regression was used to determine if FOHR was correlated with neuropsychological scores. RESULTS: Forty patients met the inclusion criteria; 26 (65%) had shunted hydrocephalus. Age at neuropsychological testing was 10.9 ± 0.6 years. FOHR was greater in the shunted group (0.64 vs 0.51; P < .001). There were no differences in neuropsychological results between shunted and nonshunted groups. On univariable analysis, greater FOHR was associated with lower FSIQ (P = .025) and lower Visual Spatial Index scores (P = .013), which remained significant on multivariable analysis after adjusting for gestational age at birth, lesion level, shunt status, and shunt revision status (P = .049 and P = .006, respectively). Separate analyses by shunt status revealed that these effects were driven by the shunted group. CONCLUSIONS: Greater FOHR before shunting was correlated with lower FSIQ and the Visual Spatial Index scores on the Weschler Intelligence Scales. Larger studies are needed to explore further the relationship between ventricle size, hydrocephalus, and neurodevelopmental outcomes.

Machine learning in prenatal MRI predicts postnatal ventricular abnormalities in fetuses with isolated ventriculomegaly.

OBJECTIVES: To evaluate the intracranial structures and brain parenchyma radiomics surrounding the occipital horn of the lateral ventricle in normal fetuses (NFs) and fetuses with ventriculomegaly (FVs), as well as to predict postnatally enlarged lateral ventricle alterations in FVs. METHODS: Between January 2014 and August 2023, 141 NFs and 101 FVs underwent 1.5 T balanced steady-state free precession (BSSFP), including 68 FVs with resolved lateral ventricles (FVM-resolved) and 33 FVs with stable lateral ventricles (FVM-stable). Demographic data and intracranial structures were analyzed. To predict the enlarged ventricle alterations of FVs postnatally, logistic regression models with 5-fold cross-validation were developed based on lateral ventricle morphology, blended-cortical or/and subcortical radiomics characteristics. Validation of the models' performance was conducted using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). RESULTS: Significant alterations in cerebral structures were observed between NFs and FVs (p < 0.05), excluding the maximum frontal horn diameter (FD). However, there was no notable distinction between the FVM-resolved and FVM-stable groups (all p > 0.05). Based on subcortical-radiomics on the aberrant sides of FVs, this approach exhibited high efficacy in distinguishing NFs from FVs in the training/validation set, yielding an impressive AUC of 1/0.992. With an AUC value of 0.822/0.743 in the training/validation set, the Subcortical-radiomics model demonstrated its ability to predict lateral ventricle alterations in FVs, which had the greatest predictive advantages indicated by DCA. CONCLUSIONS: Microstructural alterations in subcortical parenchyma associated with ventriculomegaly can serve as predictive indicators for postnatal lateral ventricle variations in FVs. CLINICAL RELEVANCE STATEMENT: It is critical to gain pertinent information from a solitary fetal MRI to anticipate postnatal lateral ventricle alterations in fetuses with ventriculomegaly. This approach holds the potential to diminish the necessity for recurrent prenatal ultrasound or MRI examinations. KEY POINTS: Fetal ventriculomegaly is a dynamic condition that affects postnatal neurodevelopment. Machine learning and subcortical-radiomics can predict postnatal alterations in the lateral ventricle. Machine learning, applied to single-fetal MRI, might reduce required antenatal testing.

Prenatal diagnosis and pregnancy outcomes in fetuses with ventriculomegaly.

Objective: Genetic etiology plays a critical role in fetal ventriculomegaly (VM). However, the studies on chromosomal copy number variants (CNVs) in fetal VM are limited. This study aimed to investigate the chromosomal CNVs in fetuses with mild to moderate VM, and explore its genotype-phenotype correlation. Methods: A total of 242 fetuses with mild to moderate VM detected by prenatal ultrasound were enrolled in our study from October 2018 to October 2022. All cases underwent chromosomal microarray analysis (CMA) and G-banding simultaneously. All VM cases were classified different subgroups according to the maternal age, severity, VM distribution and presence/absence of other ultrasound abnormalities. The pregnancy outcomes and health conditions after birth were followed up. We also performed a pooled analysis regarding likely pathogenic and pathogenic CNVs (LP/P CNVs) for VM. Results: The detection rate of chromosomal abnormalities by karyotyping was 9.1% (22/242), whereas it was 16.5% (40/242) when CMA was conducted (P < 0.05). The total detection rate of chromosomal abnormalities by karyotyping and CMA was 21.1% (51/242). A 12.0% incremental yield of CMA over karyotyping was observed. The detection rate of total genetic variants in fetuses with bilateral VM was significantly higher than in fetuses with unilateral VM (30.0% vs. 16.7%, P = 0.017). No significant differences were discovered between isolated VM and non-isolated VM, or between mild and moderate VM, or between advanced maternal age (AMA) and non-AMA (all P > 0.05). 28 fetuses with VM were terminated and 214 fetuses were delivered: one presented developmental delay and one presented congenital heart disease. The VM cases with both positive CMA and karyotypic results had a higher rate of termination of pregnancy than those with either a positive CMA or karyotypic result, or both negative testing results (P < 0.001). Conclusion: The combination of CMA and karyotyping should be adopted to improve the positive detection rate of chromosomal abnormalities for VM. The total genetic abnormalities detected using both techniques would affect the final pregnancy outcomes. LP/P CNVs at 16p11.2, 17p13, and 22q11.21 were identified as the top three chromosomal hotspots associated with VM, which would enable genetic counselors to provide more precise genetic counseling for VM pregnancies.

Perinatal and neurodevelopmental outcomes of fetal isolated ventriculomegaly: a systematic review and meta-analysis.

Background: Isolated fetal ventriculomegaly can have a range of consequences, ranging from mild neurodevelopmental delay to perinatal death; the extent of these consequences often depend on the severity of ventriculomegaly. This systematic review and meta-analysis aims to investigate the impact of the degree of ventricular dilatation on the risk of neurodevelopmental delay and adverse perinatal outcomes in fetuses diagnosed with isolated fetal ventriculomegaly from gestational week 15 onwards. Methods: PubMed, Embase, Scopus and the Cochrane Library were searched electronically to identify studies investigating the prognosis of mild and/or severe isolated fetal ventriculomegaly. Articles were included if they reported neurodevelopmental or perinatal outcomes in fetuses prenatally diagnosed with isolated fetal ventriculomegaly from week 15 of gestation and onwards. Studies were excluded if they reported on non-isolated ventriculomegaly (IVM), failed to specify the degree of ventriculomegaly, were non-English papers, animal studies or published outside of the 21-year period of interest. Study quality was assessed by two independent reviewers using a modified version of the Newcastle-Ottawa Quality Assessment Scale. Ventriculomegaly was defined as either mild or severe when ventricular diameter measured as 10-15 or >15 mm, respectively. Meta-analyses were conducted for adverse neurodevelopmental outcome, intrauterine fetal demise and infant mortality. Results: Following the removal of duplicates, the search yielded 2,452 citations, of which 23 studies were included and 8 were eligible for meta-analysis. There were 767 and 347 cases of mild and severe isolated fetal ventriculomegaly, respectively. Adverse outcomes were consistently reported at a higher rate in severe cases than mild. The relative risks of adverse neurodevelopmental outcome, intrauterine fetal demise and infant mortality were 4.24 [95% confidence interval (CI): 2.46-7.30], 4.46 (95% CI: 1.64-12.11) and 6.02 (95% CI: 1.73-21.00), respectively, upon comparison of mild versus severe cases of isolated fetal ventriculomegaly. Conclusions: The likelihood of adverse neurodevelopmental and perinatal outcomes, including intrauterine and infant mortality, is increased in severe isolated fetal ventriculomegaly compared to mild isolated fetal ventriculomegaly.

Fetal Cerebral Ventriculomegaly: A Narrative Review and Practical Recommendations for Pediatric Neurologists.

Fetal cerebral ventriculomegaly is one of the most common fetal neurological disorders identified prenatally by neuroimaging. The challenges in the evolving landscape of conditions like fetal cerebral ventriculomegaly involve accurate diagnosis and how best to provide prenatal counseling regarding prognosis as well as postnatal management and care of the infant. The purpose of this narrative review is to discuss the literature on fetal ventriculomegaly, including postnatal management and neurodevelopmental outcome, and to provide practice recommendations for pediatric neurologists.

Utility of intracranial pressure monitoring as a diagnostic tool in pediatric ventriculomegaly.

OBJECTIVE: Intracranial pressure (ICP) monitoring is commonly utilized for identifying pathologic ICP in cases of traumatic brain injury; however, its utility in hydrocephalic children has not been elucidated. Although patients with typical (pressure-active) hydrocephalus present with clear signs and/or symptoms and the need for cerebrospinal fluid (CSF) diversion is often clear, others may have arrested or pressure-compensated hydrocephalus with pathologic ICP elevation masked by ambiguous signs or are completely asymptomatic. Without treatment these pathologic ICP elevations may affect neurologic development or crescendo over time leading to neurological decline. The purpose of this study is to investigate the utility of ICP monitoring as a diagnostic tool in this relatively common patient population and identify ventriculomegaly patients with and without pathologic ICP, thus improving accuracy of identifying those with and without surgical needs. METHODS: 36 patients (≤ 17 years old) underwent 41 inpatient ICP recording sessions between 2016 and 2022 and were retrospectively reviewed. This included patients with a history of severe, nonprogressive ventriculomegaly and normal fundoscopic examinations lacking traditional signs and symptoms concerning for elevated ICP. Nighttime pathological plateau waves were defined as sustained elevations of ICP ≥ 2x baseline for a duration of ≥ 5 minutes. RESULTS: The mean age of patients was 5.5 years old (range 0-17 years old). 46.3% of patients had prior endoscopic third ventriculostomy (ETV), 14.6% had prior ventriculoperitoneal shunt (VPS), and 39% were without prior surgical intervention. Roughly half (51.2%) of patients had congenital ventriculomegaly while other patients had ventriculomegaly due to other pathologies such as germinal matrix hemorrhage/intraventricular hemorrhage (GMH/IVH) (29.3%), stroke (4.9%), cerebral infections/meningitis (2.4%), or unknown etiology (12.2%). The average procedure time was 19.1 ± 10.5 minutes, and mean length of stay was 2.8 ± 0.7 days. Pathologic ICP was demonstrated in 12 cases (29.3%), 4 (33.3%) of which were asymptomatic. Pathologic ICP was found in 7 of 19 (36.8%) in the prior ETV group, 1 of 6 (16.7%) in prior shunt group, and 4 of 16 (25%) in the non-surgical group (p = 0.649). Among those with pathologic ICP, 6 (50%) cases received an ETV, 5 (41.7%) cases underwent VPS placement, and 1 (8.3%) case underwent a VPS revision. There were no infectious complications or cases of hemorrhage. 4 patients required repositioning of the ICP monitor due to dislodgement. CONCLUSION: Inpatient ICP monitoring is a safe and effective diagnostic tool for evaluating the presence of pathologic ICP in severe, persistent non-progressive ventriculomegaly. The use of ICP monitoring may aid in identifying patients with pressure-compensated hydrocephalus who demonstrate pathologic ICP where surgical intervention may be warranted, while preventing unnecessary CSF diversion in those without pathology.

Secondary normal pressure hydrocephalus following pituitary apoplexy: A case report.

Background: Although secondary normal pressure hydrocephalus (sNPH) can occur in various central nervous system diseases, there are no reports of sNPH caused by pituitary lesions. Herein, we present a unique case of sNPH caused by pituitary apoplexy. Case Description: A 70-year-old man was transferred to our hospital because of a sudden onset of headache and loss of consciousness. The cerebrospinal fluid (CSF) test showed slightly elevated cell counts and protein levels but a negative CSF culture test. Magnetic resonance imaging showed a dumbbell-like cystic lesion with hemorrhagic change at the sella turcica. From the above, the patient was diagnosed with aseptic meningitis caused by pituitary apoplexy. Pituitary hormone replacement therapy was undertaken, and his symptoms fully improved. However, two months later, he complained of a gait disturbance and incontinence that had gradually appeared. Brain imaging with computed tomography showed no ventricular enlargement compared with initial images, although the lateral ventricles were slightly enlarged. As a CSF drainage test improved his symptoms temporarily, sNPH with possible longstanding overt ventriculomegaly in adults (LOVA) background was suspected. We performed a lumboperitoneal shunt (LPS) placement, which improved his symptoms. Conclusion: This case suggests that sNPH can develop even after a small subarachnoid hemorrhage caused by a pituitary apoplexy in LOVA patients. If the aqueduct of Sylvius is open, sNPH with a LOVA background can be successfully treated with LPS placement.

A ventriculomegaly feature computational pipeline to improve the screening of normal pressure hydrocephalus on CT.

OBJECTIVE: The objective of this study was to develop a computational pipeline that extracts objective features of ventriculomegaly from non-contrast CT (NCCT) for the accurate classification of idiopathic normal pressure hydrocephalus (NPH) from headache controls (HCs), Alzheimer's dementia (AD), and posttraumatic encephalomalacia (PTE). METHODS: Patients with possible NPH (n = 79) and a subset with definite NPH (DefNPH; n = 29) were retrospectively identified in the Veterans Affairs Informatics and Computing Infrastructure system, along with the AD (n = 62), PTE (n = 53), and HC (n = 59) cohorts. Image-processing pipelines were developed to extract a novel feature capturing the maximum eccentricity of the lateral ventricles (MaxEccLV), a proxy splenial angle (p-SA), the Evans indices (EI-x, -y, and -z), callosal angle, normalized maximum third-ventricle width, and CSF to brain volume ratio from their NCCT scans. The authors used t-tests to examine group differences in the features and multivariate logistic regression models for classification. Additionally, the NPH versus HC classifier was validated on external data. RESULTS: When NPH and DefNPH were compared with HC, AD, and PTE, significant differences were found in all features except the p-SA, which only significantly differed between NPH and PTE. The test-set area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were 0.98, 100%, and 98.3% for NPH versus HC classification; 0.94, 87.3%, and 85.5% for NPH versus AD; 0.96, 92.4%, and 90.6% for NPH versus PTE; and 0.96, 94%, and 88% for NPH versus the other groups using logistic regression under five-fold cross-validation. Consistently high performance was noted for DefNPH. The NPH versus HC classifier provided an AUC of 0.84, sensitivity of 76.9%, and specificity of 90% when assessed on external data. CONCLUSIONS: Including the novel MaxEccLV, this framework computes useful features of ventriculomegaly, which had not previously been algorithmically assessed on NCCT. This framework successfully classified possible and definite NPH from HC, AD, and PTE. Following validation on larger representative cohorts, this objective and accessible tool may aid in screening for NPH and differentiating it from symptomatic mimics such as AD and PTE.

ESCRT-I protein UBAP1 controls ventricular expansion and cortical neurogenesis via modulating adherens junctions of radial glial cells.

Intricate cerebral cortex formation is orchestrated by the precise behavior and division dynamics of radial glial cells (RGCs). Endocytosis functions in the recycling and remodeling of adherens junctions (AJs) in response to changes in RGC activity and function. Here, we show that conditional disruption of ubiquitin-associated protein 1 (UBAP1), a component of endosomal sorting complex required for transport (ESCRT), causes severe brain dysplasia and prenatal ventriculomegaly. UBAP1 depletion disrupts the AJs and polarity of RGCs, leading to failure of apically directed interkinetic nuclear migration. Accordingly, UBAP1 knockout or knockdown results in reduced proliferation and precocious differentiation of neural progenitor cells. Mechanistically, UBAP1 regulates the expression and surface localization of cell adhesion molecules, and ß-catenin over-expression significantly rescues the phenotypes of Ubap1 knockdown in vivo. Our study reveals a critical physiological role of the ESCRT machinery in cortical neurogenesis by regulating AJs of RGCs.

Long-Standing Overt Ventriculomegaly in Adults (LOVA) With Absent Septum Pellucidum and Spontaneous Ventriculostomy: Report of a Rare Case.

Long-standing overt ventriculomegaly in adults (LOVA) is a type of chronic hydrocephalus with presumable infant onset characterized by macrocephaly and massive ventriculomegaly that causes clinical presentations in later adult life. We report a case of a 20-year-old man who was referred from the ophthalmology department for further investigation of his visual disturbances. MRI of the head revealed massive ventriculomegaly with an Evan's index of 0.44. A careful investigation revealed coexisting aqueductal stenosis, absent septum pellucidum, ventricular rupture, and spontaneous ventriculostomy. The clinical presentations were relatively mild compared to his MRI findings. He was referred to a neurosurgeon for potential surgical interventions after the administration of conservative hyperosmolar drugs and neuroprotective agents.

Follow-up outcome analysis of 324 cases of early-onset and late-onset mild fetal ventriculomegaly: a retrospective cohort study.

BACKGROUND: Mild fetal ventriculomegaly (VM) is a nonspecific finding common to several pathologies with varying prognosis and is, therefore, a challenge in fetal consultation. We aimed to perform a constant, detailed analysis of prenatal findings and postnatal outcomes in fetuses with early-onset and late-onset mild ventriculomegaly, and provide a new evidence basis and new perspective for prenatal counseling. METHODS: This is a retrospective cohort study of women with a diagnosis of mild fetal VM between January 2018 and October 2020. The population was divided into two groups according to the gestational ages (GAs) at initial diagnosis: the early-onset group (diagnosed at/before 24+6 weeks) and the late-onset group (diagnosed after 24+6 weeks). Clinical data and pregnancy outcomes were obtained from hospital records. The children's neurodevelopment status was assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3) and telephone interviews. RESULTS: Our study cohort comprised 324 fetuses, out of which 94 (29%) were classified as early-onset group and 230 (71%) late-onset group. Early-onset group was more likely to have concurrent additional abnormalities, whereas in the late-onset group, isolated enlargement was more common (P = 0.01). Unilateral enlargement was more common in the late-onset group (P = 0.05), and symmetrical enlargement in the early-onset group (P < 0.01). In addition, early-onset mild VM cases were more likely to have intrauterine progression (P = 0.03), and many had a higher proportion of complex multisystem abnormalities. Compared with the late-onset group, the early-onset group was more often associated with congenital brain structure malformations. Approximately 11% of fetuses with mild VM had postnatal neurodevelopmental delay/disorders, and the risk was higher in the early-onset group (19.4% vs. 7.4%). Regression analysis showed that the GA at first diagnosis, non-isolated, and intrauterine progression significantly correlated with neurodevelopmental abnormalities. CONCLUSIONS: Early-onset and late-onset mild VM had significantly different ultrasound features and outcomes. Early-onset mild VM may have more complex potential abnormalities and are more likely to predict poor prognosis than the late-onset.

Prenatal Diagnosis of Fetal Aqueductal Stenosis: A Multicenter Prospective Observational Study through the North American Fetal Therapy Network.

INTRODUCTION: A critical component of an evidence-based reassessment of in-utero intervention for fetal aqueductal stenosis (fetal AS) is determining if the prenatal diagnosis can be accurately made at a gestational age amenable to in-utero intervention. METHODS: A multicenter, prospective, observational study was conducted through the North American Fetal Therapy Network (NAFTNet). Pregnancies complicated by severe central nervous system (CNS) ventriculomegaly (lateral ventricle diameter >15 mm) not secondary to a primary diagnosis (myelomeningocele, encephalocele, etc.) were recruited at diagnosis. Imaging and laboratory findings were recorded in an online REDCap database. After evaluation, investigators were asked to render their degree of confidence in the diagnosis of fetal AS. The prenatal diagnosis was compared to the postnatal diagnosis obtained through neonatal neuroimaging. Performance characteristics of ultrasound and magnetic resonance imaging (MRI) were calculated, as was the mean gestational age at diagnosis. RESULTS: Between April 2015 and October 2022, eleven NAFTNet centers contributed 64 subjects with severe fetal CNS ventriculomegaly. Of these, 56 had both prenatal and postnatal diagnoses recorded. Ultrasound revealed 32 fetal AS true positives, 4 false positives, 7 false negatives, and 13 true negatives, rendering a sensitivity of 0.82, a specificity of 0.76, a positive predictive value of 0.89, and a negative predictive value of 0.65. The mean gestational age at diagnosis by ultrasound was 25.5 weeks (std +/- 4.7 weeks). The proportion of agreement (true positive + true negative/n) was highest at 24 weeks gestation. For fetal MRI (n = 35), the sensitivity for fetal AS was 0.95, specificity was 0.69, positive predictive value was 0.84, and negative predictive value was 0.90. MRI was performed at 25 weeks on average. CONCLUSION: The prenatal diagnosis of fetal AS can be made with accuracy at a gestational age potentially amenable to in-utero intervention. Only 7% of subjects were incorrectly diagnosed prenatally with fetal AS by ultrasound and 11% by MRI. Diagnostic accuracy of fetal AS will likely improve with increased experience.