Search

The Commander complex is required for endosomal recycling of diverse transmembrane cargos and is mutated in Ritscher-Schinzel syndrome. It comprises two sub-assemblies: Retriever composed of VPS35L, VPS26C, and VPS29; and the CCC complex which contains twelve subunits: COMMD1-COMMD10 and the coiled-coil domain-containing (CCDC) proteins CCDC22 and CCDC93. Combining X-ray crystallography, electron cryomicroscopy, and in silico predictions, we have assembled a complete structural model of Commander. Retriever is distantly related to the endosomal Retromer complex but has unique features preventing the shared VPS29 subunit from interacting with Retromer-associated factors. The COMMD proteins form a distinctive hetero-decameric ring stabilized by extensive interactions with CCDC22 and CCDC93. These adopt a coiled-coil structure that connects the CCC and Retriever assemblies and recruits a 16th subunit, DENND10, to form the complete Commander complex. The structure allows mapping of disease-causing mutations and reveals the molecular features required for the function of this evolutionarily conserved trafficking machinery., Competing Interests: Declaration of interests The authors declare that they have no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Endoscopic third ventriculostomy/choroid plexus cauterization (ETV/CPC) has gained popularity in its treatment of infantile hydrocephalus over the past decade. In this manuscript, we perform a systematic review and meta-analysis to determine the efficacy and safety of ETV/CPC, and to compare the procedural outcomes between North American and sub-Saharan African cohorts. Methods: Systematic review was performed using four electronic databases and bibliographies of relevant articles, with no language or date restrictions. Cohort studies of participants undergoing ETV/CPC that reported outcome were included using MOOSE guidelines. The outcome was time to repeat CSF diversion or death. Forest plots were created for pooled mean and its 95 % CI of outcome and morbidity. Results: Of 78 citations, 11 retrospective reviews (with 524 total participants) were eligible. Efficacy was achieved in 63 % participants at follow-up periods between 6 months and 8 years. Adverse events and mortality was reported in 3.7 and 0.4 % of participants, respectively. Publication bias was detected with respect to efficacy and morbidity of the procedure. A large discrepancy in success was identified between ETV/CPC in six studies from sub-Saharan Africa (71 %), compared to three studies from North America (49 %). Conclusions: The reported success of ETV/CPC for infantile hydrocephalus is higher in sub-Saharan Africa than developed nations. Large long-term prospective multi-center observational studies addressing patient-important outcomes are required to further evaluate the efficacy and safety of this re-emerging procedure. [ABSTRACT FROM AUTHOR]

Objectives: The relationships between shunt infection and predictive factors have not been previously investigated using Artificial Neural Network (ANN) model. The aim of this study was to develop an ANN model to predict shunt infection in a group of children with shunted hydrocephalus. Materials and methods: Among more than 800 ventriculoperitoneal shunt procedures which had been performed between April 2000 and April 2011, 68 patients with shunt infection and 80 controls that fulfilled a set of meticulous inclusion/exclusion criteria were consecutively enrolled. Univariate analysis was performed for a long list of risk factors, and those with p value < 0.2 were used to create ANN and logistic regression (LR) models. Results: Five variables including birth weight, age at the first shunting, shunt revision, prematurity, and myelomeningocele were significantly associated with shunt infection via univariate analysis, and two other variables (intraventricular hemorrhage and coincided infections) had a p value of less than 0.2. Using these seven input variables, ANN and LR models predicted shunt infection with an accuracy of 83.1 % (AUC; 91.98 %, 95 % CI) and 55.7 % (AUC; 76.5, 95 % CI), respectively. The contribution of the factors in the predictive performance of ANN in descending order was history of shunt revision, low birth weight (under 2000 g), history of prematurity, the age at the first shunt procedure, history of intraventricular hemorrhage, history of myelomeningocele, and coinfection. Conclusion: The findings show that artificial neural networks can predict shunt infection with a high level of accuracy in children with shunted hydrocephalus. Also, the contribution of different risk factors in the prediction of shunt infection can be determined using the trained network. [ABSTRACT FROM AUTHOR]

Background: The middle meningeal artery (MMA) is often sacrificed during neurosurgical procedures in the region of the pterion. This maneuver, herein, is hypothesized to be a potential reason for the development of postoperative hydrocephalus by injuring the vascular supply to the arachnoid granulations near the vertex of the skull, and thus disrupting their ability to allow for transfer of CSF from the subarachnoid space to the venous system. Materials and methods: To test this theory, the middle meningeal artery was isolated at the skull base and injected with India ink. Next, the superior sagittal sinus was opened and the arachnoid granulations inspected. Results: All specimens demonstrated ink within the arachnoid granulations indicating that their blood supply is completely or at least partially via the middle meningeal artery. This finding with an illustrative case of surgical cautery of the middle meningeal artery at the skull base with subsequent development of hydrocephalus supports our hypothesis of potential role of iatrogenic MMA injury causing hydrocephalus. Conclusions: Our cadaveric study shows that the blood supply of the arachnoid granulations of the superior sagittal sinus is via the middle meningeal artery. Additional cases of postoperative hydrocephalus following middle meningeal artery sacrifice are needed to support our hypothesis. [ABSTRACT FROM AUTHOR]

New-onset psychotic symptoms often respond well to antipsychotic treatment; however, symptoms may be difficult to treat when an underlying brain malformation is present. Here, we present a case of atypical psychotic symptoms in the context of a congenital cerebellar malformation (Dandy–Walker variant). The patient ultimately improved with paliperidone palmitate after multiple antipsychotic medication trials (both oral and one long-acting injectable) were ineffective. Neuroimaging may provide valuable diagnostic and prognostic information in cases of new-onset psychosis with atypical features and treatment resistance, even in the absence of neurologic signs and symptoms. [ABSTRACT FROM PUBLISHER]

Dandy-Walker malformation, which is a congenital malformation of the cerebellum, is documented in literature to be associated with psychotic symptoms, obsessive compulsive symptoms, mood symptoms, hyperactivity, and impulsive behavior. The pathogenesis of psychiatric symptoms in Dandy-Walker malformation is thought to be due to disruption of the corticocerebellar tracts, resulting in what is known as cerebellar cognitive affective syndrome. We present a case of Dandy-Walker malformation presenting with psychiatric symptoms. This case highlights the necessity to be aware of psychiatric manifestations of cerebellar disease as it has an impact on the diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Marinesco-Sjögren syndrome (MSS) is a rare autosomal recessive disorder, which is characterized by congenital cataracts, cerebellar ataxia, progressive muscle weakness, and delayed psychomotor development. SIL1 , which is located at 5q31.2, is the only gene known to cause MSS. Dandy-Walker syndrome (DWS) is defined by hypoplasia, upward rotation of the cerebellar vermis, and cystic dilation of the fourth ventricle; however, its genetic pathogeny remains unclear. Here, we report a Chinese consanguineous family with MSS and DWS. Whole exome sequencing identified a novel nonstop mutation in SIL1 . Sanger sequencing revealed that the mutation was segregated in this family according to a recessive mode of inheritance. We found that the mutation changed a stop codon (TGA) to an arginine codon (CGA), and no in-frame termination codon in the 3′ untranslated region (UTR) of SIL1 could be found. The mRNA levels of SIL1 were decreased by 56.6% and 37.5% in immortalized lymphoblasts of the patients respectively; the protein levels of SIL1 were substantially decreased. This case study is the first report on Chinese MSS patients, MSS complicated by DWS, and a nonstop mutation in SIL1 . Our findings imply the pathogenetic association between DWS and MSS. [ABSTRACT FROM AUTHOR]

ABSTRACT We describe two cases in which delayed rotation of the cerebellar vermis simulated a Dandy-Walker malformation ( DWM) on early second-trimester magnetic resonance imaging ( MRI). Two pregnant women with suspected fetal posterior fossa anomaly on ultrasound examination underwent fetal MRI at 21 (Case 1) and 19 (Case 2) weeks' gestation. In both cases, upward rotation of the cerebellar vermis was noted; on midsagittal imaging, the brainstem-vermis angle was 28° and 43°, respectively, while cerebellar morphometry showed a reduced vermian anteroposterior diameter compared to reference data. The posterior fossa appeared to be mildly enlarged, while all other findings were normal. Follow-up MRI at 28 + 3 weeks' gestation (Case 1) and at 1 postnatal year (Case 2) showed completely normal findings. Both children had normal psychomotor development and neurological examinations at 1 year of age. Incomplete rotation of the cerebellar vermis can be a physiological finding on early second-trimester fetal MRI examination and can simulate DWM or other forms of cerebellar hypoplasia. Embryologically, delayed permeabilization of Blake's pouch could account for the delayed vermian rotation. Follow-up imaging at a later gestational age is crucial to ensure that this condition is not over-reported and to avoid the potential risk of unnecessary pregnancy interruption. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objectives: Diagnosis of isolated posterior fossa anomalies in children is biased by the fact that only those that are symptomatic are brought to the attention of the appropriate clinical personnel, and the reported rate is often affected by the adoption of different nomenclature, diagnostic criteria, outcome measures, duration of follow-up and neurodevelopmental tools. The aim of this systematic review was to explore the neurodevelopmental outcome of fetuses with a prenatal diagnosis of isolated posterior fossa anomalies.Methods: MEDLINE and EMBASE were searched electronically, utilizing combinations of the relevant medical subject heading terms for 'posterior fossa' and 'outcome'. Studies assessing the neurodevelopmental outcome in children with a prenatal diagnosis of isolated posterior fossa malformations were considered eligible. The posterior fossa anomalies analyzed included Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC) and vermian hypoplasia (VH). Two authors reviewed all abstracts independently. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. Meta-analyses of proportions were used to combine data, and between-study heterogeneity was explored using the I(2) statistic.Results: A total of 1640 articles were identified; 95 were assessed for eligibility and a total of 16 studies were included in the systematic review. The overall rate of abnormal neurodevelopmental outcome in children with a prenatal diagnosis of DWM was 58.2% (95% CI, 21.8-90.0%) and varied from 0-100%. In those with a prenatal diagnosis of MCM, the rate of abnormal neurodevelopmental outcome was 13.8% (95% CI, 7.3-21.9%), with a range of 0-50%. There was no significant association between BPC and the occurrence of abnormal neurodevelopmental delay, with a rate of 4.7% (95% CI, 0.7-12.1%) and range of 0-5%. Although affected by the very small number of studies, there was a non-significant occurrence of abnormal neurodevelopmental delay in children with a prenatal diagnosis of VH, with a rate of 30.7% (95% CI, 0.6-79.1%) and range of 0-100%.Conclusions: Fetuses diagnosed with isolated DWM are at high risk of abnormal neurodevelopmental outcome, while isolated MCM or BPC have a generally favorable outcome. The risk of abnormal developmental delay in cases with isolated VH needs to be further assessed. In view of the wide heterogeneity in study design, time of follow-up, neurodevelopmental tests used and the very small number of included cases, further future large prospective studies with standardized and objective protocols for diagnosis and follow-up are needed in order to ascertain the rate of abnormal neurodevelopmental outcome in children with isolated posterior fossa anomalies. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To describe the sonographic appearance of fetal posterior fossa anatomy at 11-14 weeks of pregnancy and to assess the outcome of fetuses with increased intracranial translucency (IT) and/or brainstem-to-occipital bone (BSOB) diameter.Methods: Reference ranges for brainstem (BS), IT and cisterna magna (CM) measurements, BSOB diameter and the BS : BSOB ratio were obtained from the first-trimester ultrasound examination of 233 fetuses with normal postnatal outcome (control group). The intraobserver and interobserver variability of measurements were investigated using 73 stored ultrasound images. In addition, a study group of 17 fetuses with increased IT and/or BSOB diameter was selected to assess outcome.Results: No significant intraobserver or interobserver variability was found for any measurement in the control group. In the study group, IT was increased in all cases and BSOB diameter was above the 95(th) centile of the calculated normal range in all but two (88%) cases. In 13/17 study cases, only two of the three posterior brain spaces were recognized on ultrasound. These 13 fetuses had a larger BSOB diameter than did the four cases that showed all three posterior brain spaces, and had severe associated anomalies including Dandy-Walker malformation (DWM) and/or chromosomal anomalies.Conclusions: Visualization of the fetal posterior fossa anatomy at 11-14 weeks' gestation is feasible. Increased fluid in the posterior brain at 11-14 weeks, particularly in the case of non-visibility of the septation that divides the future fourth ventricle from the CM, is an important risk factor for cystic posterior fossa malformations, in particular DWM, and/or chromosomal aberrations. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Objective: To explore the outcome in fetuses with prenatal diagnosis of posterior fossa anomalies apparently isolated on ultrasound imaging.Methods: MEDLINE and EMBASE were searched electronically utilizing combinations of relevant medical subject headings for 'posterior fossa' and 'outcome'. The posterior fossa anomalies analyzed were Dandy-Walker malformation (DWM), mega cisterna magna (MCM), Blake's pouch cyst (BPC) and vermian hypoplasia (VH). The outcomes observed were rate of chromosomal abnormalities, additional anomalies detected at prenatal magnetic resonance imaging (MRI), additional anomalies detected at postnatal imaging and concordance between prenatal and postnatal diagnoses. Only isolated cases of posterior fossa anomalies - defined as having no cerebral or extracerebral additional anomalies detected on ultrasound examination - were included in the analysis. Quality assessment of the included studies was performed using the Newcastle-Ottawa Scale for cohort studies. We used meta-analyses of proportions to combine data and fixed- or random-effects models according to the heterogeneity of the results.Results: Twenty-two studies including 531 fetuses with posterior fossa anomalies were included in this systematic review. The prevalence of chromosomal abnormalities in fetuses with isolated DWM was 16.3% (95% CI, 8.7-25.7%). The prevalence of additional central nervous system (CNS) abnormalities that were missed at ultrasound examination and detected only at prenatal MRI was 13.7% (95% CI, 0.2-42.6%), and the prevalence of additional CNS anomalies that were missed at prenatal imaging and detected only after birth was 18.2% (95% CI, 6.2-34.6%). Prenatal diagnosis was not confirmed after birth in 28.2% (95% CI, 8.5-53.9%) of cases. MCM was not significantly associated with additional anomalies detected at prenatal MRI or detected after birth. Prenatal diagnosis was not confirmed postnatally in 7.1% (95% CI, 2.3-14.5%) of cases. The rate of chromosomal anomalies in fetuses with isolated BPC was 5.2% (95% CI, 0.9-12.7%) and there was no associated CNS anomaly detected at prenatal MRI or only after birth. Prenatal diagnosis of BPC was not confirmed after birth in 9.8% (95% CI, 2.9-20.1%) of cases. The rate of chromosomal anomalies in fetuses with isolated VH was 6.5% (95% CI, 0.8-17.1%) and there were no additional anomalies detected at prenatal MRI (0% (95% CI, 0.0-45.9%)). The proportions of cerebral anomalies detected only after birth was 14.2% (95% CI, 2.9-31.9%). Prenatal diagnosis was not confirmed after birth in 32.4% (95% CI, 18.3-48.4%) of cases.Conclusions: DWM apparently isolated on ultrasound imaging is a condition with a high risk for chromosomal and associated structural anomalies. Isolated MCM and BPC have a low risk for aneuploidy or associated structural anomalies. The small number of cases with isolated VH prevents robust conclusions regarding their management from being drawn. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. [ABSTRACT FROM AUTHOR]

Aim: Tuberculous meningitis (TBM) is a lethal and commonly occurring form of extra-pulmonary tuberculosis in children, often complicated by hydrocephalus which worsens outcome. Despite high mortality and morbidity, little data on the impact on neurodevelopment exists. We examined the clinical characteristics, and clinical and neurodevelopmental outcomes of TBM and hydrocephalus.Method: Demographic and clinical data (laboratory and radiological findings) were prospectively collected on children treated for probable and definite TBM with hydrocephalus. At 6 months, clinical outcome was assessed using the Paediatric Cerebral Performance Category Scale and neurodevelopmental outcome was assessed with the Griffiths Mental Development Scale - Extended Version.Results: Forty-four patients (median age 3y 3mo, range 3mo-13y 1mo, [SD 3y 5mo]) were enrolled. The mortality rate was 16%, three patients (6.8%) were in a persistent vegetative state, two were severely disabled (4.5%), and 11 (25%) suffered mild-moderate disability. All cases demonstrated neurodevelopmental deficits relative to controls. Multiple or large infarcts were prognostic of poor outcome.Interpretation: Neurological and neurodevelopmental deficits are common after paediatric TBM with hydrocephalus, and appear to be related to ongoing cerebral ischaemia and consequent infarction. The impact of TBM on these children is multidimensional and presents short- and long-term challenges. [ABSTRACT FROM AUTHOR]

The human cerebellum has a protracted development that makes it vulnerable to a broad spectrum of developmental disorders including malformations and disruptions. Starting from 19 to 20 weeks of gestation, prenatal magnetic resonance imaging (MRI) can reliably study the developing cerebellum. Pre- and postnatal neuroimaging plays a key role in the diagnostic work-up of congenital cerebellar abnormalities. Diagnostic criteria for cerebellar malformations and disruptions are based mostly on neuroimaging findings. The diagnosis of a Dandy-Walker malformation is based on the presence of hypoplasia, elevation, and counterclockwise upward rotation of the cerebellar vermis and cystic dilatation of the fourth ventricle, which extends posteriorly filling out the posterior fossa. For the diagnosis of Joubert syndrome, the presence of the molar tooth sign (thickened, elongated, and horizontally orientated superior cerebellar peduncles and an abnormally deep interpeduncular fossa) is needed. The diagnostic criteria of rhombencephalosynapsis include a complete or partial absence of the cerebellar vermis and continuity of the cerebellar hemispheres across the midline. Unilateral cerebellar hypoplasia is defined by the complete aplasia or hypoplasia of one cerebellar hemisphere. Familiarity with these diagnostic criteria as well as the broad spectrum of additional neuroimaging findings is important for a correct pre- and postnatal diagnosis. A correct diagnosis is essential for management, prognosis, and counseling of the affected children and their family. [ABSTRACT FROM AUTHOR]

Dandy-Walker syndrome (DWS) is a congenital brain malformation that is characterized by partial or complete agenesis of the cerebellar vermis and cystic dilatation of the 4th ventricle that shifts ventrolaterally to displace the cerebellar hemispheres. This case is a 68-year-old male veteran with complaints of new-onset cognitive disorder who was found to have previously unsuspected DWS on head computed tomography. This is one of the first case studies to present complete neuropsychological test results in a veteran with DWS. Despite the level of abnormality on imaging, the veteran functioned well until onset of mild cognitive impairments in late adulthood. [ABSTRACT FROM AUTHOR]

Neurocutaneous melanosis is a rare congenital disorder characterized by the presence of large or multiple congenital melanocytic cutaneous nevi associated with intracranial leptomeningeal melanocytosis. An association with Dandy-Walker malformation has been reported in 8-10% of children with neurocutaneous melanosis.[1] The main objective of this case report is to present the rare association as only few cases have been reported in literature, besides, as well, to discuss this as a case that appeared to be as meningitis with posterior fossa cystic malformation but turned out as neurocutaneous melanosis with Dandy-Walker malformation. In addition, we wanted to highlight the importance of correlating clinical examination findings with imaging findings and not limiting to imaging findings alone. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 8-year-old male with X chromosome-linked Dandy–Walker syndrome. It is mentioned that biopsy revealed that atrophic corneal epithelium with intact Bowman's layer. The article discusses that the child's visual acuity of 6 out of 7.5 however, the signs resembled Salzmann's nodular degeneration and severe eye malformations including bilateral microphthalmia and microcornea.

Background: Etiologies of hydrocephalus are many and sometimes it can be attributed to be multifactorial in origin. Presence of known cause of hydrocephalus like fourth ventricular pathology may mask foramenal stenosis. Diagnosis of unilateral and bilateral stenosis of foramen of Monro should be included in the treatment plan in hydrocephalus A case report of a 9 months-old boy presented with delayed milestones of development and an increase in head circumference. The patient has been diagnosed as hydrocephalus and associated Dandy-Walker malformation. Ventriculoperitoneal shunt was inserted successfully but drained only one lateral ventricle. The association of isolated lateral ventricle with Dandy-Walker malformation is due to stenosis of foramen of Monro. Our case report is unique due to association between foramen occlusion and Dandy-Walker malformation. [ABSTRACT FROM AUTHOR]

Abstract: We report a case of long‐standing overt ventriculomegaly without aqueductal stenosis. A 66‐year‐old woman developed progressive gait disturbance. Her gait was wide‐based, with a difficulty in turning. Prominent macrocephaly was present, which suggests the presence of long‐standing hydrocephalus since childhood. Cognitive impairments were detected on neuropsychological tests. Cerebral magnetic resonance imaging revealed marked enlargement of the third and lateral ventricles. Aqueductal stenosis was not apparent; however, endoscopic third ventriculostomy partly ameliorated gait disturbance. Endoscopic third ventriculostomy can be a therapeutic option for long‐standing overt ventriculomegaly even if the aqueduct is patent. [ABSTRACT FROM AUTHOR]

Most hypotheses trying to explain the pathophysiology of idiopathic syringomyelia involve mechanisms whereby CSF is pumped against a pressure gradient, from the subarachnoid space into the cord parenchyma. On review, these theories have universally failed to explain the disease process. A few papers have suggested that the syrinx fluid may originate from the cord capillary bed itself. However, in these papers, the fluid is said to accumulate due to impaired fluid drainage out of the cord. Again, there is little evidence to substantiate this. This proffered hypothesis looks at the problem from the perspective that syringomyelia and normal pressure hydrocephalus are almost identical in their manifestations but only differ in their site of effect within the neuraxis. It is suggested that the primary trigger for syringomyelia is a reduction in the compliance of the veins draining the spinal cord. This reduces the efficiency of the pulse wave dampening, occurring within the cord parenchyma, increasing arteriolar and capillary pulse pressure. The increased capillary pulse pressure opens the blood-spinal cord barrier due to a direct effect upon the wall integrity and interstitial fluid accumulates due to an increased secretion rate. An increase in arteriolar pulse pressure increases the kinetic energy within the cord parenchyma and this disrupts the cytoarchitecture allowing the fluid to accumulate into small cystic regions in the cord. With time the cystic regions coalesce to form one large cavity which continues to increase in size due to the ongoing interstitial fluid secretion and the hyperdynamic cord vasculature. [ABSTRACT FROM AUTHOR]

Timely management of hydrocephalus in infants is critical as the initial treatment can have lifelong implications for survival and neurological outcome. In the developing countries, grossly enlarged heads are still not an uncommon occurrence. In extreme cases, there may be a spontaneous rupture of hydrocephalus either externally or internally, depending on the status of the sutures. Here, the successful management of a rare complication of spontaneous rupture of hydrocephalus in an infant is discussed. The management of the present case provides a novel approach to deal with this dreaded complication. Though the neurological outcome remains guarded in such cases, they need to be tackled cautiously to address the hydrocephalus and esthetic appearance of the infant. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Perioperative management of a patient with Dandy-Walker malformation (DWM) with tetralogy of Fallot (TOF), patent ductus arteriosus, and pulmonary artery stenosis is a great challenge to the anesthesiologist. Anesthetic management in such patients can trigger tet spells that might rapidly increase intracranial pressure (ICP), conning and even death. The increase in ICP can precipitate tet spells and further brain hypoxia. To avoid an increase in ICP during TOF corrective surgery ventriculo-peritoneal (VP) shunt should be performed before cardiac surgery. We present the first case report of a 11-month-old male baby afflicted with DWM and TOF who underwent successful TOF total corrective surgery and fresh autologous pericardial pulmonary valve conduit implantation under cardiopulmonary bypass after 1 week of VP shunt insertion. [ABSTRACT FROM AUTHOR]

Background: Kabuki syndrome is a rare hereditary disease affecting multiple organs. The causative genes identified to date are KMT2D and KDMA6. The aim of this study is to evaluate the clinical manifestations and the spectrum of mutations of KMT2D. Methods: We retrospectively retrieved a series of eight patients from two hospitals in China and conducted Sanger sequencing for all of the patients and their parents if available. We also reviewed the literature and plotted the mutation spectrum of KMT2D. Results: The patients generally presented with typical clinical manifestations as previously reported in other countries. Uncommon symptoms included spinal bifida and Dandy-Walker malformation. With respect to the mutations, five mutations were found in five patients, including two frameshift indels, one nonsense mutation and two missense mutations. Conclusions: This is the first case series on Kabuki syndrome in Mainland China. Unusual symptoms, such as spinal bifida and Dandy-Walker syndrome, suggested that neurological developmental defects may accompany Kabuki syndrome. This case series helps broaden the mutation spectrum of Kabuki syndrome and adds information regarding the manifestations of Kabuki syndrome. [ABSTRACT FROM AUTHOR]

Background: Meckel-Gruber syndrome (MGS) is a classic triad of occipital encephalocele, postaxial polydactyly and dysplastic cystic kidney with or without other associated malformations. Dandy-Walker malformation (DWM) is the association of three signs: hydrocephalus, partial or complete absence of the cerebellar vermis, and posterior fossa cyst contiguous with the fourth ventricle. Methodology: A 30 weeks dead fetus fixed in formalin was sent at Genetic Health And Research Center, Nasik for further evaluation. It was diagnosed by ultrasonography as Dandy walker syndrome with multiple congenital anomalies. Autopsy finding confirmed that it was Meckel's Gruber syndrome. Results & Discussion: Meckel-Gruber syndrome is extremely heterogenous syndrome with six different loci and it inherits in families as autosomal recessive disease with 25% of chance of recurrence in each pregnancy. MGS affects multiple organ systems of the body leading to many other pathological conditions such as Arnold-Chiari malformation or Dandy-Walker malformation. It is suggested to be caused by failure of the mesodermal induction leading to ciliopathies caused by dysfunction of cilia. The occurrence of a Dandy-Walker malformation in Meckel-Gruber syndrome confirms disturbance in rhombencephalon development and such variants are very uncommon. Many cases of Dandy Walker Syndome as such have been published throughout but Dandy Waker associated with Meckel's Gruber Syndrome is extremely rare. Conclusion: We propose that proper autopsy of all still birth should be conducted to guide parents for possible risks in subsequent pregnancies. Prenatal and postnatal counseling and prenatal diagnosis should be encouraged in all disease prone cases. [ABSTRACT FROM AUTHOR]

Joubert syndrome is a neurologic disorder with a pathognomonic “molar tooth sign” on brain imaging. The purpose of this study was to identify potential mutations in a Chinese patient with Joubert syndrome by targeted massively parallel sequencing. Taking advantage of high-throughput DNA sequencing technologies, 18 Joubert-causing genes of a Chinese patient with classic Joubert syndrome were sequenced at a time, and 2 novel variants in the CEP290 gene (c.7323_7327delAGAAG and c.6012-2A>G) were identified in this patient. Sanger validation showed that 2 variants were inherited from each parents, respectively. Both variants are located in the C-terminal region of the CEP290 protein and are predicted to be deleterious. The results support that the combination of targeted genes enrichment and next-generation sequencing is valuable molecular diagnostic tool and suitable for clinical application. [ABSTRACT FROM PUBLISHER]

Background: Dandy-Walker syndrome (DWS) is a congenital disorder often diagnosed in early childhood. Typically manifesting with signs/symptoms of increased intracranial pressure, DWS is catastrophic unless timely neurosurgical care can be administered via cerebrospinal fluid (CSF) drainage. The rates of mortality, adverse discharge disposition (ADD), and CSF drainage in DWS may not be uniform regardless of race, gender or insurance status; such differences could reflect disparities in access to neurosurgical care. This study examines these issues on a nationwide level. Materials and Methods: The Kids' Inpatient Database spanning 1997-2003 was used for analysis. Only patients admitted for DWS (ICD-9-CM = 742.3) were included. Multivariate analysis was adjusted for several variables, including patient age, race, sex, admission type, primary payer, income, and hospital volume. Results: More than 14,000 DWS patients were included. Increasing age predicted reduced mortality (OR = 0.87; P < 0.05), ADD (OR = 0.96; P < 0.05), and decreased likelihood of receiving CSF drainage (OR = 0.86; P < 0.0001). Elective admission type predicted reduced mortality (OR = 0.29; P = 0.0008), ADD (OR = 0.68; P < 0.05), and increased CSF drainage (OR = 2.02; P < 0.0001). African-American race (OR = 1.20; P < 0.05) and private insurance (OR = 1.18; P < 0.05) each predicted increased likelihood of receiving CSF drainage, but were not predictors of mortality or ADD. Gender, income, and hospital volume were not significant predictors of DWS outcome. Conclusion: Increasing age and elective admissions each decrease mortality and ADD associated with DWS. African-American race and private insurance status increase access to CSF drainage. These findings contradict previous literature citing African-American race as a risk factor for mortality in DWS, and emphasize the role of private insurance in obtaining access to potentially lifesaving operative care. [ABSTRACT FROM AUTHOR]

Background Cerebrospinal fluid (CSF) shunt infection is a major cause of morbidity and mortality in the treatment of hydrocephalus and is associated with significant medical cost. Several studies have demonstrated the efficacy of antibiotic-impregnated (AI) shunt catheters in reducing CSF shunt infection; however, providers remain reluctant to adopt AI catheters into practice because of the increased upfront cost. The objective of this study was to determine if the use of AI catheters provided cost savings in a large nationwide database. Methods Hospital discharge and billing records from the Premier Perspective Database from 2003–2009 were retrospectively reviewed to identify all adult and pediatric patients undergoing de novo ventricular shunt placement. The incidence of shunt infection within 1 year of implantation was determined. Shunt infection–related cost was defined as all inpatient billing costs incurred during hospitalization for treatment of shunt infection. Results In 287 U.S. hospitals, 10,819 adult (AI catheters, 963; standard catheters, 9856) and 1770 pediatric (AI catheters, 229; standard catheters, 1541) patients underwent ventricular shunt placement. AI catheters were associated with significant reduction in infection for both adult (2.2% vs. 3.6%, P = 0.02) and pediatric (2.6% vs. 7.1%, P < 0.01) patients. Total infection-related costs were $17,371,320 ($45,714 ± $49,745 per shunt infection) for adult patients and $6,508,064 ($56,104 ± $65,746 per shunt infection) for pediatric patients. Infection-related cost per 100 de novo shunts placed was $120,534 for AI catheters and $162,659 for standard catheters in adult patients and $165,087 for AI catheters and $395,477 for standard catheters in pediatric patients. Conclusions In analysis of this large, nationwide database, AI catheters were found to be associated with a significant reduction in infection incidence, resulting in tremendous cost savings. AI catheters were associated with a cost savings of $42,125 and $230,390 per 100 de novo shunts placed in adult and pediatric patients, respectively. [ABSTRACT FROM AUTHOR]

Background: Reliable prognostic tools to estimate the case fatality rate (CFR) and the development of chronic hydrocephalus (CHC) in aneurysmal subarachnoid hemorrhage (SAH) are not well defined. This study aims to investigate the practicability and reliability of Fisher, Graeb, and LeRoux scores for SAH patient prognosis. Methods: A total of 206 patients with aneurysmal SAH were retrospectively analyzed in prediction of CFR and CHC. Clinical data was evaluated and grading was performed using Fisher, Graeb, and LeRoux scores. Univariate and multivariate analyses were performed to identify relevant predictive parameters. Results: CFR was 17.0 % and was associated with higher age, higher Hunt & Hess (H&H) grade, lower Glasgow Coma Scale (GCS) at admission, as well as a higher Fisher, Graeb, and LeRoux score ( p < 0.001). There were 19.9 % that developed CHC requiring permanent cerebrospinal fluid diversion. Low initial GCS ( p = 0.003), high H&H ( p < 0.001), intracerebral hematoma ( p = 0.003), high Fisher ( p = 0.047), Graeb and LeRoux scores ( p < 0.001) were associated with a higher rate of ventricular-peritoneal shunting (VPS) in surviving patients. In multivariate analyses, Graeb score (odds ratio (OR) 1.183 [1.027, 1.363], p = 0.020), LeRoux score (OR 1.120 [1.013-1.239, p = 0.027), and H&H (OR 2.715 [1.496, 4.927], p = 0.001) remained independent prognostic factors for VPS. Conclusions: Graeb or LeRoux scores improve the prediction of shunt dependency and in parts of CFR in aneurysmal SAH patients therefore confirming the relevance of the extent and distribution of intraventricular blood for the clinical course in SAH. [ABSTRACT FROM AUTHOR]

Background: Hydrocephalus is common in patients with open neural tube defects (NTDs), but association with closed NTDs has rarely been reported. We describe three patients with untreated closed NTDs who required surgery for hydrocephalus. Case reports: Case 1: A full-term newborn presented with a skin-covered midline lumbar spine lipoma. Magnetic resonance imaging (MRI) scan demonstrated a lipomyelomeningocele. An ultrasound at birth showed mild ventriculomegaly but cerebrospinal fluid diversion was not offered because his fontanelle was soft. He was lost to follow-up and then presented at age 6 months with signs and symptoms of hydrocephalus. An endoscopic third ventriculostomy and choroid plexus coagulation were performed, and the lipomyelomeningocele was subsequently repaired electively. Case 2: A full-term neonate presented with a skin-covered midline lumbar spine lesion consistent with a meningocele on MRI scan. He was additionally noted to have macrocephaly, a full fontanelle, and ventriculomegaly on MRI scan. At age 2 days, an endoscopic third ventriculostomy and choroid plexus coagulation were performed. A ventriculoperitoneal shunt was required 1 month later. Three months after birth, an elective spinal cord untethering procedure was performed. Case 3: A neonate presented with a midline lumbar skin tag. An MRI scan demonstrated a lipomyelomeningocele, and surgery was planned electively. On preoperative evaluation at age 3 months, the patient had a tense fontanelle. The surgery was postponed, and a ventriculoperitoneal shunt was placed after imaging studies revealed hydrocephalus. Conclusion: Patients with closed NTDs should be assessed for clinical signs and symptoms of hydrocephalus because of this rare but possible association. [ABSTRACT FROM AUTHOR]

Objective: Multiloculated hydrocephalus may occur as a consequence of intraventricular hemorrhage or infection and is characterized by enlargement of multiple noncommunicating intraventricular and/or periventricular cysts. In this study, we report the outcomes of open and endoscopic fenestration for multiloculated hydrocephalus at our institution. Methods: Records of children who underwent endoscopic or open fenestration at St. Louis Children's Hospital from 1999 to 2011 were analyzed. The cause of MLH, operative parameters, length of hospital stay, and subsequent shunt intervention rate were recorded. Results: Twenty-five subjects were identified for study. Twelve subjects underwent open craniotomy and 13 underwent endoscopic fenestration. Endoscopic fenestration was associated with decreased blood loss, operative time, and length of stay ( p = 0.003, 0.002, 0.02, respectively). Subjects undergoing craniotomy had an average of 5.1 ± 4.5 subsequent shunt-related interventions versus 3.1 ± 4.0 in the endoscopy group ( p = 0.25). The craniotomy group's median subsequent shunt revision rate was 0.74 interventions per year versus 0.50 interventions per year in the endoscopy group ( p = 0.51). Fifty percent of subjects in the open fenestration group required additional fenestration surgery compared to 38.5 % in the endoscopic group ( p = 0.70). Conclusion: Both open and endoscopic fenestration appeared effective at improving shunt management. The endoscopic technique may offer advantages in operative time, blood loss, and length of hospital stay. These data suggest that endoscopic fenestration may be used as the initial approach for treatment of multiloculated hydrocephalus, with craniotomy and open fenestration used for more severe or refractory cases. [ABSTRACT FROM AUTHOR]

Object: The goal of this study is to evaluate whether an 'ideal shunt' exists. Methods: This is a retrospective analysis based on original papers in the field of Hydrocephalus and Shunts. Patients of all age groups, who had hydrocephalus, and underwent some form of CSF diversion were included. The study has been divided into four stages: from 1900 to 1949, 1950 to 1974, 1975 to 1999, and from 2000 to 2010. Results: In stage 1 ( historical era): Saphenous vein grafts, rubber conduits, and other materials were used in CSF diversions. In 1949, the first implantable shunt tube was developed by Nulsen. In stage 2 ( experimental stage): the Holter valve was developed. Newer innovations were developed in relation to the ventriculo-atrial shunt, which was the preferred CSF diversion. In stage 3 ( developmental stage), a large number of different design shunt systems were developed, with the aim of reducing complications. The ventriculo-peritoneal shunt had become the preferred CSF diversion. Also, the programmable valve was born. In stage 4 ( era of programmable valve, there is a preference for the use of programmable shunt systems. However, shunt failure rate at 1 year being around 25 to 40 %, and shunt survival at 1 and 2 years are 50-70 and 47-53 % in most series. Conclusion: Every shunt is an ideal shunt provided the choice of the shunt used should be made by the matching performance of the shunt system to the altered profile of CSF dynamics of a given patient. The most important factor being the opening pressure. [ABSTRACT FROM AUTHOR]

Background: Dandy-Walker syndrome (DWS) is a congenital disorder typically manifesting with hydrocephalus. The classic anatomic hallmarks of DWS are hypoplasia of the cerebellar vermis, anterior-posterior enlargement of the posterior fossa, upward displacement of the torcula and transverse sinuses, and cystic dilatation of the fourth ventricle. Aims: Although optimal treatment of DWS typically requires neurosurgical intervention to prevent intracranial pressure increases incompatible with life, the natural history of this disorder has yet to be evaluated on a nationwide level. Settings and Design/Materials and Methods: The Kids' Inpatient Database covering 1997-2003 was used for analysis. Children younger than age 18 admitted for DWS (ICD-9-CM = 742.3) were analyzed with a matched control group. The primary procedure codes for operative CSF drainage were coded into the analysis. The incidence of DWS was 0.136%; 14,599 DWS patients were included. Statistical Analysis Used: Multiple logistic regression models were used. Odds ratios (OR) were reported with 95% confidence intervals. Results and Conclusions: Mortality (OR = 10.02; P < 0.0001) and adverse discharge disposition (OR = 4.59; P < 0.0001) were significantly greater in DWS patients compared with controls. 20.4% of DWS patients received operative cerebrospinal fluid (CSF) drainage, 81-times more than controls (P < 0.0001). CSF drainage reduced mortality by 44% among DWS patients (P < 0.0001). Although DWS is associated with a 10-fold increase in mortality, operative CSF drainage nearly halves the mortality rate. Based on these findings (Class IIB evidence), it is likely that the increased mortality associated with DWS is directly attributable to the nearly 80% of DWS patients who did not receive operative CSF drainage for hydrocephalus. Consequently, increased access to neurosurgical intervention could reduce the mortality rate of DWS towards that of the general population. [ABSTRACT FROM AUTHOR]

Hydrocephalus is a very common disease in developing countries. Congenital aqueductal obstruction and post-inflammatory hydrocephalus come on the top of the list of causes of hydrocephalus. Till the recent introduction of cranial endoscopy and despite their frequent complications, shunts were considered as the mainstream treatment for this disease. Endoscopic third ventriculostomy (ETV), especially for obstructive hydrocephalus, introduced a new era of treatment that is free of lifetime shunt dependency. This study was done to assess the efficacy of ETV for treating post-inflammatory hydrocephalus in a unique group of patients thus preventing-if possible-the lifetime shunt dependency and suffering. ETV was tried as a first-line therapy in 35 children (23 males and 12 females) with hydrocephalus proved to be secondary to intracranial infection. Mean age was 9.2 months (4-15). Twenty-four patients (68.6 %) were below the age of 6 months while 11 patients (31.4 %) were above 6 months. Twenty-five patients (71.4 %) had a head circumference of 3 cm and 10 patients (28.6 %) had a 5 cm or more increase in the head circumference above the 95th percentile. All the patients included were followed postoperatively with regular clinical, computerized tomography (CT), and magnetic resonance imaging (MRI) examinations as well as cerebrospinal fluid (CSF) analysis and culture. The overall success of ETV was 55.9 % (19/34). Nine (81.9 %) out of the 11 patients that were endoscopically documented to have aqueductal obstruction showed improvement. While out of the 23 patients with patent aqueduct, only 10 patients (43.4 %) had improved. Procedure-related complications were not encountered. CSF leakage from the surgical wound occurred in three patients and mild CSF infection occurred in one patient. ETV is a simple, safe, and effective method in treating not only obstructive hydrocephalus due to non-inflammatory etiology, but also post-inflammatory hydrocephalus especially when the aqueduct is obstructed. An overall 50 % improvement in our study and even more in other series encourage the trial of getting rid of the lifetime shunt complications and suffering. [ABSTRACT FROM AUTHOR]

Copyright of Collegium Antropologicum is the property of Croatian Anthropological Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The Dandy-Walker syndrome (DWS) is a rare posterior fossa malformation. The DWS can occur associated with other brain or systemic malformations, but ocular abnormalities in this disease are rare and clinical findings mimicking myasthenia gravis have not been described to date. We report a 23-year-old woman who presented mild limitation of the ocular movements with progressive palpebral ptosis, which changed in intensity during the day. The investigation showed negative anti-acetylcholine receptor antibody, repetitive nerve stimulation and "Tensilon test", but the brain magnetic resonance image reveals DWS with hydrocephalus associated with calosal dysgenesis. The characteristic of disease, clinical manifestations and pathologic features, specially the clinical evaluation of ocular abnormalities in suspicion of DWS, including the MG in differential diagnosis are discussed.A síndrome de Dandy-Walker (DWS) é uma rara malformação da fossa posterior que pode ocorrer associada com outras malformações cerebrais ou sistêmicas. As alterações oculares são raras e as manifestações clínicas, simulando miastenia gravis (MG), não foram descritas até o momento. Descrevemos uma mulher de 23 anos apresentando discreta limitação da movimentação ocular com progressiva ptose palpebral que mudava de intensidade durante o dia. A investigação mostrou negativos o anticorpo anti-receptor de acetilcolina, a estimulação nervosa repetitiva e o "teste do Tensilon", porém a ressonância magnética de crânio revelou DWS com hidrocefalia associada à disgenesia de corpo caloso. As características da doença, manifestações clínicas e patológicas, especialmente a avaliação clínica de anormalidade ocular na suspeita de DWS serão discutidas, incluindo a MG no diagnóstico diferencial.