Changes In Ventricle Size Research Articles

Ultrasonography for Serial Monitoring and Management of Cerebrospinal Fluid Dynamic Disorders After Decompressive Craniectomy.

Decompressive craniectomy (DC) is widely used to treat intracranial hypertension following severe head injury. However, impairments of cerebrospinal fluid (CSF) hydrodynamics such as hydrocephalus and subdural effusion are common complications that occur after DC. Therefore, monitoring of intracranial pressure is a staple of neurocritical care post-DC. The aim of this study was to assess the usefulness of transcranial duplex sonography (TDS) for serial monitoring and management of CSF disorders after DC. A total of 100 patients who underwent DC between June 2016 and May 2019 were recruited for the study. Transcranial duplex sonography examinations were performed between 1-day and 1-year post-DC. Transcranial duplex sonography was mainly used for monitoring changes in ventricle size and morphology, and also to monitor intraventricular hemorrhage, hydrocephalus, intracranial hygromas, and ventricle changes during CSF release procedures. A total of 456 TDS examinations were performed on patients after DC. Of these, 402 were performed in the neuro-intensive care unit. Two patients had intraventricular hemorrhage and underwent TDS-guided external ventricular drainage. Twenty-nine patients were diagnosed with hydrocephalus. The results of TDS were consistent with those of cranial computed tomography. Three cases of ventriculoperitoneal shunt and 1 case of lumbar peritoneal shunt underwent valve pressure reset according to TDS, to obtain satisfactory ventricle size. Transcranial duplex sonography was used to monitor ventricle changes and control drainage volume during CSF release procedures, including 2 external ventricular drainage, 6 external lumbar drainage, and 10 lumbar punctures. Eighteen patients were detected with single or multiple intracranial effusions, including 16 subdural hygromas, 5 longitudinal fissure hygromas, and 6 brain cysts. Transcranial duplex sonography can efficiently help monitor changes in ventricle size and morphology and intracranial effusions. Due to its noninvasive nature, suitability for bedside application, real-time, and inexpensiveness, TDS can significantly replace cranial computed tomography and become part of the patient's daily inspection work after DC.

A Combined Human in Silico and CRISPR/Cas9-Mediated in Vivo Zebrafish Based Approach to Provide Phenotypic Data for Supporting Early Target Validation.

The clinical heterogeneity of heart failure has challenged our understanding of the underlying genetic mechanisms of this disease. In this respect, large-scale patient DNA sequencing studies have become an invaluable strategy for identifying potential genetic contributing factors. The complex aetiology of heart failure, however, also means that in vivo models are vital to understand the links between genetic perturbations and functional impacts as part of the process for validating potential new drug targets. Traditional approaches (e.g., genetically-modified mice) are optimal for assessing small numbers of genes, but less practical when multiple genes are identified. The zebrafish, in contrast, offers great potential for higher throughput in vivo gene functional assessment to aid target prioritisation, by providing more confidence in target relevance and facilitating gene selection for definitive loss of function studies undertaken in mice. Here we used whole-exome sequencing and bioinformatics on human patient data to identify 3 genes (API5, HSPB7, and LMO2) suggestively associated with heart failure that were also predicted to play a broader role in disease aetiology. The role of these genes in cardiovascular system development and function was then further investigated using in vivo CRISPR/Cas9-mediated gene mutation analysis in zebrafish. We observed multiple impacts in F0 knockout zebrafish embryos (crispants) following effective somatic mutation, including changes in ventricle size, pericardial oedema, and chamber malformation. In the case of lmo2, there was also a significant impact on cardiovascular function as well as an expected reduction in erythropoiesis. The data generated from both the human in silico and zebrafish in vivo assessments undertaken supports further investigation of the potential roles of API5, HSPB7, and LMO2 in human cardiovascular disease. The data presented also supports the use of human in silico genetic variant analysis, in combination with zebrafish crispant phenotyping, as a powerful approach for assessing gene function as part of an integrated multi-level drug target validation strategy.

Endoscopic Third Ventriculostomy for an Idiopathic Disproportionately Large Communicating Fourth Ventricle: A Case Report

A disproportionately large communicating fourth ventricle (DLCFV) is a rare condition. A 34-year-old man experienced severe headaches, nausea, vomiting, and gait disturbance. Initial brain computed tomography (CT) showed markedly dilated ventricles with prepontine cistern shrinkage. Following extraventricular drain (EVD) insertion, approximately 400 mL/d of cerebrospinal fluid (CSF) was removed over 8 days. During this time, no significant changes in ventricle size were observed on CT images or the facial pain scale (FPS). We then performed an endoscopic third ventriculostomy and changed the drainage catheter. Immediately after surgery, the patient’s symptoms were relieved, and the drainage volume gradually decreased. EVD was successfully removed on the eighth postoperative day. Our experiences suggest that neurosurgeons should consider the importance of a third ventriculostomy for the diagnosis and treatment of DLCFV.

Prevalence and characteristics of shunt malfunction without ventricular size change at King Abdulaziz Medical City in Riyadh.

Objectives:To determine the prevalence of shunt malfunction without change in ventricle size in imaging modalities, and its clinical presentation.Methods:A cross-sectional study conducted at King Abdulaziz Medical City, Riyadh, from June 2015 to May 2019. Patient’s demographics, clinical presentation and changes in ventricle size were collected. Statistical analysis was done using SPSS version 23.Results:The study included 42 patients who underwent shunt revision. Imaging showed no change in size in 10 (24%) patients, mild enlargement in 8 (19%), and obvious enlargement in 24 (57%). The mean age of diagnosis was 22±16.7. 55% of the patients were males, 45% females. The cause of the malfunction was ventricular catheter occlusion in 14 (34%) patients, 10 (24%) patients had valve-related malfunction, and peritoneal catheter occlusion was present in 6 (14%) patients, and 12 (28%) patients had a combination of the previously mentioned causes. Analysis of the association between ventricular size and headache, vomiting, seizure, confusion, and loss of consciousness in patients with unchanged ventricular size and those with increased ventricular size has shown no statistical significance.Conclusion:Shunt malfunction without ventricular size change was observed in 24% of all shunt malfunction patients. In addition, there was no relationship between ventricular size and patient symptoms.

Ventricular Volume Is More Strongly Associated with Clinical Improvement Than the Evans Index after Shunting in Idiopathic Normal Pressure Hydrocephalus.

Ventricular enlargement in idiopathic normal pressure hydrocephalus is often estimated using the Evans index. However, the sensitivity of the Evans index to estimate changes in ventricular size postoperatively has been questioned. Here, we evaluated the postoperative change in ventricle size in relation to shunt response in patients with idiopathic normal pressure hydrocephalus, by comparing ventricular volume and the Evans index. Fifty-seven patients with idiopathic normal pressure hydrocephalus underwent high-resolution MR imaging preoperatively and 6 months after shunt insertion. Clinical symptoms of gait, balance, cognition, and continence were assessed according to the idiopathic normal pressure hydrocephalus scale. The ventricular volume of the lateral and third ventricles and the Evans index were measured using ITK-SNAP software. Semiautomatic volumetric analysis was performed, and postoperative changes in ventricular volume and the Evans index and their relationships to postoperative clinical improvement were compared. The median postoperative ventricular volume decrease was 25 mL (P < .001). The proportional decrease in ventricular volume was greater than that in the Evans index (P < .001). The postoperative decrease in ventricular volume was associated with a postoperative increase in the idiopathic normal pressure hydrocephalus scale score (P = .004). Shunt responders (75%) demonstrated a greater ventricular volume decrease than nonresponders (P = .002). Clinical improvement after shunt surgery in idiopathic normal pressure hydrocephalus is associated with a reduction of ventricular size. Ventricular volume is a more sensitive estimate than the Evans index and, therefore, constitutes a more precise method to evaluate change in ventricle size after shunt treatment in idiopathic normal pressure hydrocephalus.

Examining the Progressive Behavior and Neuropathological Outcomes Associated with Chronic Repetitive Mild Traumatic Brain Injury in Rats.

While the physical and behavioral symptomologies associated with a single mild traumatic brain injury (mTBI) are typically transient, repetitive mTBIs (RmTBI) have been associated with persisting neurological deficits. Therefore, this study examined the progressive changes in behavior and the neuropathological outcomes associated with chronic RmTBI through adolescence and adulthood in male and female Sprague Dawley rats. Rats experienced 2 mTBIs/week for 15 weeks and were periodically tested for changes in motor behavior, cognitive function, emotional disturbances, and aggression. Brain tissue was examined for neuropathological changes in ventricle size and presentation of Iba1 and GFAP. We did not see progressively worse behavioral impairments with the accumulation of injuries or time, but did find evidence for neurological and functional change (motor disturbance, reduced exploration, reduced aggression, alteration in depressive-like behavior, deficits in short-term working memory). Neuropathological assessment of RmTBI animals identified an increase in ventricle size, prolonged changes in GFAP, and sex differences in Iba1, in the corpus callosum, thalamus, and medial prefrontal cortex. Telomere length reduced exponentially as the injury load increased. Overall, chronic RmTBI did not result in accumulating behavioral impairment, and there is a need to further investigate progressive behavioral changes associated with repeated injuries in adolescence and young adulthood.

Predictors of endoscopic third ventriculostomy ostomy status in patients who experience failure of endoscopic third ventriculostomy with choroid plexus cauterization.

At failure of endoscopic third ventriculostomy (ETV) with choroid plexus cauterization (CPC), the ETV ostomy may be found to be closed or open. Failure with a closed ostomy may indicate a population that could benefit from evolving techniques to keep the ostomy open and may be candidates for repeat ETV, whereas failure with an open ostomy may be due to persistently abnormal CSF dynamics. This study seeks to identify clinical and radiographic predictors of ostomy status at the time of ETV/CPC failure. The authors conducted a multicenter, retrospective cohort study on all pediatric patients with hydrocephalus who failed initial ETV/CPC treatment between January 2013 and October 2016. Failure was defined as the need for repeat ETV or ventriculoperitoneal (VP) shunt placement. Clinical and radiographic data were collected, and ETV ostomy status was determined endoscopically at the subsequent hydrocephalus procedure. Statistical analysis included the Mann-Whitney U-test, Wilcoxon rank-sum test, t-test, and Pearson chi-square test where appropriate, as well as multivariate logistic regression. Of 72 ETV/CPC failures, 28 patients (39%) had open-ostomy failure and 44 (61%) had closed-ostomy failure. Patients with open-ostomy failure were older (median 5.1 weeks corrected age for gestation [interquartile range (IQR) 0.9-15.9 weeks]) than patients with closed-ostomy failure (median 0.2 weeks [IQR -1.3 to 4.5 weeks]), a significant difference by univariate and multivariate regression. Etiologies of hydrocephalus included intraventricular hemorrhage of prematurity (32%), myelomeningocele (29%), congenital communicating (11%), aqueductal stenosis (11%), cyst/tumor (4%), and other causes (12%). A wider baseline third ventricle was associated with open-ostomy failure (median 15.0 mm [IQR 10.3-18.5 mm]) compared to closed-ostomy failure (median 11.7 mm [IQR 8.9-16.5 mm], p = 0.048). Finally, at the time of failure, patients with closed-ostomy failure had enlargement of their ventricles (frontal and occipital horn ratio [FOHR], failure vs baseline, median 0.06 [IQR 0.00-0.11]), while patients with open-ostomy failure had no change in ventricle size (median 0.01 [IQR -0.04 to 0.05], p = 0.018). Previous CSF temporizing procedures, intraoperative bleeding, and time to failure were not associated with ostomy status at ETV/CPC failure. Older corrected age for gestation, larger baseline third ventricle width, and no change in FOHR were associated with open-ostomy ETV/CPC failure. Future studies are warranted to further define and confirm features that may be predictive of ostomy status at the time of ETV/CPC failure.

Cerebrospinal Fluid Lumbar Tapping Utilization for Suspected Ventriculoperitoneal Shunt Under-Drainage Malfunctions.

ObjectiveThe diagnosis of shunt malfunction can be challenging since neuroimaging results are not always correlated with clinical outcomes. The purpose of this study was to evaluate the efficacy of a simple, minimally invasive cerebrospinal fluid (CSF) lumbar tapping test that predicts shunt under-drainage in hydrocephalus patients.MethodsWe retrospectively reviewed the clinical and radiological features of 48 patients who underwent routine CSF lumbar tapping after ventriculoperitoneal shunt (VPS) operation using a programmable shunting device. We compared shunt valve opening pressure and CSF lumbar tapping pressure to check under-drainage.ResultsThe mean pressure difference between valve opening pressure and CSF lumbar tapping pressure of all patients were 2.21±24.57 mmH2O. The frequency of CSF lumbar tapping was 2.06±1.26 times. Eighty five times lumbar tapping of 41 patients showed that their VPS function was normal which was consistent with clinical improvement and decreased ventricle size on computed tomography scan. The mean pressure difference in these patients was −3.69±19.20 mmH2O. The mean frequency of CSF lumbar tapping was 2.07±1.25 times. Fourteen cases of 10 patients revealed suspected VPS malfunction which were consistent with radiological results and clinical symptoms, defined as changes in ventricle size and no clinical improvement. The mean pressure difference was 38.07±23.58 mmH2O. The mean frequency of CSF lumbar tapping was 1.44±1.01 times. Pressure difference greater than 35 mmH2O was shown in 2.35% of the normal VPS function group (2 of 85) whereas it was shown in 64.29% of the suspected VPS malfunction group (9 of 14). The difference was statistically significant (p=0.000001). Among 10 patients with under-drainage, 5 patients underwent shunt revision. The causes of the shunt malfunction included 3 cases of proximal occlusion and 2 cases of distal obstruction and valve malfunction.ConclusionUnder-drainage of CSF should be suspected if CSF lumbar tapping pressure is 35 mmH2O higher than the valve opening pressure and shunt malfunction evaluation or adjustment of the valve opening pressure should be made.

Pediatric hydrocephalus: systematic literature review and evidence-based guidelines. Part 10: Change in ventricle size as a measurement of effective treatment of hydrocephalus.

The objective of this systematic review is to answer the following question: Does ventricle size after treatment have a predictive value in determining the effectiveness of surgical intervention in pediatric hydrocephalus? The US National Library of Medicine PubMed/MEDLINE database and the Cochrane Database of Systematic Reviews were searched using MeSH headings and key words relevant to change in ventricle size after surgical intervention for hydrocephalus in children. An evidentiary table was assembled summarizing the studies and the quality of evidence (Classes I-III). Six articles satisfied inclusion criteria for the evidentiary tables for this part of the guidelines. All were Class III retrospective studies. CONCLUSIONS/RECOMMENDATIon: There is insufficient evidence to recommend a specific change in ventricle size as a measurement of the effective treatment of hydrocephalus and as a measurement of the timing and effectiveness of treatments including ventriculoperitoneal shunts and third ventriculostomies. Level III, unclear clinical certainty.

Genetic Interactions within Inositol-Related Pathways are Associated with Longitudinal Changes in Ventricle Size

The genetic etiology of late-onset Alzheimer's disease (LOAD) has proven complex, involving clinical and genetic heterogeneity and gene-gene interactions. Recent genome wide association studies in LOAD have led to the discovery of novel genetic risk factors; however, the investigation of gene-gene interactions has been limited. Conventional genetic studies often use binary disease status as the primary phenotype, but for complex brain-based diseases, neuroimaging data can serve as quantitative endophenotypes that correlate with disease status and closely reflect pathological changes. In the Alzheimer's Disease Neuroimaging Initiative cohort, we tested for association of genetic interactions with longitudinal MRI measurements of the inferior lateral ventricles (ILVs), which have repeatedly shown a relationship to LOAD status and progression. We performed linear regression to evaluate the ability of pathway-derived SNP-SNP pairs to predict the slope of change in volume of the ILVs. After Bonferroni correction, we identified four significant interactions in the right ILV (RILV) corresponding to gene-gene pairs SYNJ2-PI4KA, PARD3-MYH2, PDE3A-ABHD12B, and OR2L13-PRKG1 and one significant interaction in the left ILV (LILV) corresponding to SYNJ2-PI4KA. The SNP-SNP interaction corresponding to SYNJ2-PI4KA was identical in the RILV and LILV and was the most significant interaction in each (RILV: p = 9.13 × 10(-12); LILV: p = 8.17 × 10(-13)). Both genes belong to the inositol phosphate signaling pathway which has been previously associated with neurodegeneration in AD and we discuss the possibility that perturbation of this pathway results in a down-regulation of the Akt cell survival pathway and, thereby, decreased neuronal survival, as reflected by increased volume of the ventricles.

Enlargement of cerebral ventricles as an early indicator of encephalomyelitis.

Inflammatory disorders of the central nervous system such as multiple sclerosis and acute disseminated encephalomyelitis involve an invasion of immune cells that ultimately leads to white matter demyelination, neurodegeneration and development of neurological symptoms. A clinical diagnosis is often made when neurodegenerative processes are already ongoing. In an attempt to seek early indicators of disease, we studied the temporal and spatial distribution of brain modifications in experimental autoimmune encephalomyelitis (EAE). In a thorough magnetic resonance imaging study performed with EAE mice, we observed significant enlargement of the ventricles prior to disease clinical manifestation and an increase in free water content within the cerebrospinal fluid as demonstrated by changes in T2 relaxation times. The increase in ventricle size was seen in the lateral, third and fourth ventricles. In some EAE mice the ventricle size started returning to normal values during disease remission. In parallel to this macroscopic phenomenon, we studied the temporal evolution of microscopic lesions commonly observed in the cerebellum also starting prior to disease onset. Our data suggest that changes in ventricle size during the early stages of brain inflammation could be an early indicator of the events preceding neurological disease and warrant further exploration in preclinical and clinical studies.

Longitudinal comparison of diffusion tensor imaging parameters and neuropsychological measures following endoscopic third ventriculostomy for hydrocephalus

The authors report the case of a 25-month-old boy who underwent endoscopic third ventriculostomy (ETV) for hydrocephalus resulting from aqueductal stenosis. The patient's recovery was monitored longitudinally and prospectively using MR diffusion tensor imaging (DTI) and formal neuropsychological testing. Despite minimal change in ventricle size, improvement in the DTI characteristics and neurodevelopmental trajectory was observed following ETV. These data support the use of DTI as a biomarker to assess therapeutic response in children undergoing surgical treatment for hydrocephalus. In the patient featured in this report, DTI appeared to provide more information regarding postoperative neurodevelopmental outcome than ventricle size alone.

Genetically Engineered Mouse Mimics Schizophrenia

Back to table of contents Previous article Next article Clinical & Research NewsFull AccessGenetically Engineered Mouse Mimics SchizophreniaAaron LevinAaron LevinSearch for more papers by this authorPublished Online:5 Oct 2007https://doi.org/10.1176/pn.42.19.0022A mouse model that mirrors schizophrenia-like traits would go a long way to help researchers explore the causes and test cures for the disease. So far, the nearest scientists have gotten is dosing rodents with amphetamine or phencyclidine to mimic behavior typical of schizophrenia.A team led by Johns Hopkins researchers, however, has now developed the first transgenic mouse with a mutated gene that produces both behavioral and anatomical deficits similar to those associated with schizophrenia in humans.“We have produced a significant, if subtle, change in phenotype that can be used to test other factors or serve as a drug screen,” said Akira Sawa, M.D., Ph.D., an associate professor of psychiatry and neuroscience and director of the program in molecular psychiatry at Hopkins, in an interview. Sawa led the 15 researchers who developed the mouse.Mouse models have been developed “extremely slowly,” Douglas Meinecke, Ph.D., program officer in the Clinical Neuroscience Research Branch of the National Institute of Mental Health, told Psychiatric News. Another eight or 10 mutant genes have been identified, and some have been inserted into mice.Schizophrenia is a heterogeneous disease with multiple symptoms and causes, including genetic, said Meinecke.Sawa and colleagues created two mouse lines with a dominant-negative disrupted-in-schizophrenia (DN-DISC1) gene. Proteins expressed by DISC1 are involved in dendritic outgrowth and development of the cerebral cortex. Mutated versions of the gene have been tied to susceptibility for schizophrenia, bipolar disorder, and major depression and correlated with psychiatric disorders in an extended Scottish family, according to research published in the September 4 Proceedings of the National Academy of Sciences.“So far we've seen a lot of weakly related gene studies with small effects, including DISC1,” he said. “Now we need to perturb the gene and see what happens. What's wrong, why is it wrong, and how does it work? The new mouse models may let us look at real potential mechanisms for how the disease works.”Sawa's team found indications of anatomical changes in the transgenic mice. Left-to-right asymmetry in the lateral ventricles found in unmutated mice was lost or reversed in the DN-DISC1 mice. At 6 weeks of age, the lateral ventricles in the brain were significantly enlarged, although that difference disappeared at age 3 months.“Enlarged ventricles are important biomarkers for schizophrenia, but that is only one of several facets of the disorder and not diagnostic,” said Sawa.The researchers could not explain the initial, temporary enlargement of the ventricles.Nevertheless, because schizophrenia usually develops between the ages of 18 and 24, changes in ventricle size at least imply some role for DISC1, said Meinecke. “Simply the fact that the researchers found neurodevelopmental differences at all is important,” he said.They also found deficits that underlie abnormal neural synchrony and impaired sensorimotor gating, according to Sawa and colleagues.“Consistent abnormalities of such [schizophrenia]-associated changes can suggest that the present mouse model may mimic at least a subset of human [schizophrenia],” the researchers wrote. “Our results indicate that the enlargement of DISC1-DN is associated with deficits in neurodevelopment, but not with the process of progressive neurodegeneration.”Behavioral tests found an increase in hyperactivity, especially late in the trials, when ordinary mice should have gotten used to their surroundings. Transgenic mice took longer to find food, possibly reflecting problems either with their sense of smell or a lack of motivation. Tests for anxiety, motor coordination, and spatial learning produced no differences.A related study in the September 11 Molecular Psychiatry by Sawa's co-author and Hopkins colleague, Mikhail Pletnikov, M.D., Ph.D., found that, compared with controls, DISC1 transgenic male mice also displayed alterations in social interaction, and transgenic female mice showed deficient spatial memory, behavior similar to some features of schizophrenia.Sawa and his colleagues will next use positron emission tomography to visualize neural transmission and metabolism in the mice to help correlate the animal model to effects in human tissue, he said. They will also collaborate with other researchers, supplying mice to test how perinatal or prenatal stressors (such as some infectious diseases like toxoplasmosis) may affect the phenotype.The research was supported by grants from the U.S. Public Health Service, the Neurogenetics and Behavior Center at Johns Hopkins, the National Alliance for Research on Schizophrenia and Depression, the Stanley Medical Research Institute, and the S-R Foundation.An abstract of “Dominant-Negative DISC1 Transgenic Mice Display Schizophrenia-Associated Phenotypes Detected by Measures Translatable to Humans” is posted at<www.pnas.org/cgi/content/abstract/0704774104v1>.▪ ISSUES NewArchived

Multicenter pediatric cerebrospinal fluid shunt design trial-implications of the primary and secondary outcomes

Introduction: An international multicenter randomized trial comparing three types of valves-standard differential pressure, siphon limiting ( Delta Valve), and flow reducing (Orbis Sigma) in children undergoing their first shunt insertion has been completed. Methods: The primary outcome was shunt malfunction defined as obstruction, infection, overdrainage, or loculated ventricles. Secondary outcomes included type of shunt malfunction, change in ventricle size, surgical complications, hospital stay, patient survival, and cause of death. The primary outcome and the eligibility were blindly adjudicated in all patients. Results: 344 eligible patients were followed for a minimum of 1 year. Baseline patient characteristics were similar for each shunt group. Median age at entry was 56 days. Overall shunt failure was 39% at 1 year and 52% at 2 years. There was a 8.1% infection rate. There was no significant difference in failure rate between the three types of valves. Obstruction was the commonest cause of failure with...

Ultrasound Control of Progressive Hydrocephalus in Infancy

The authors conducted multidimensional echotomography on 119 infants to determine hydrocephalus and other disorders. The process proved quite reliable in showing changes in ventricle size. They raise the idea of conducting broad scale preventive screening among infants in danger groups to achieve early diagnosis.