Ex vivo ocular perfusion model to study vascular physiology in the mouse eye.

Several hypotheses have been tested to understand whole organ regulation in other organs such as the brain and kidney, but no such hypothesis has yet been proposed for ocular circulations. To some extent resolve this deficit our ex vivo mouse eye perfusion model takes the first step in elucidating the mechanisms controlling the individual components of the ocular circulation. Various isolated ocular vascular preparations have been utilized in studies of ocular vascular biology, physiology, and pharmacology, including studies on both normal and pathological conditions. However, there is still significant potential for further studies to improve our understanding of ocular circulation and its regulation. The choroid specifically is inaccessible to direct visualization due to the retina's high metabolic requirement with a transparency that cannot be compromised by an overly rich vascular network on the inner retinal side hindering the visualization of the choroid. In this technical paper, we provide a detailed description of all the steps to be followed from the enucleation of mouse eyes to cannulation of the ophthalmic artery and perfusion and ex vivo confocal microscopy imaging of the dynamic nature of the choroid circulation.

A clinical primer for the glymphatic system.

The complex and dynamic system of fluid flow through the perivascular and interstitial spaces of the CNS has new-found implications for neurological diseases. CSF movement throughout the CNS parenchyma is more dynamic than could be explained via passive diffusion mechanisms alone. Indeed, a semistructured glial-lymphatic (glymphatic) system of astrocyte-supported extracellular perivascular channels serves to directionally channel extracellular fluid, clearing metabolites and peptides to optimize neurological function. Clinical studies of the glymphatic network have to date proven challenging, with most data gleaned from rodent models and post-mortem investigations. However, increasing evidence suggests that disordered glymphatic function contributes to the pathophysiology of CNS ageing, neurodegenerative disease and CNS injuries, as well as normal pressure hydrocephalus. Unlocking such pathophysiology could provide important avenues towards novel therapeutics. We here provide a multidisciplinary overview of glymphatics and critically review accumulating evidence regarding its structure, function and hypothesized relevance to neurological disease. We highlight emerging technologies of relevance to the longitudinal evaluation of glymphatic function in health and disease. Finally, we discuss the translational opportunities and challenges of studying glymphatic science.

Modified Capsulorrhaphy Technique in Open Reduction of Developmental Dysplasia of the Hip.

BACKGROUND: Neglected patients with developmental dysplasia of the hip (DDH) are not uncommon. Various treatment modalities have been used. Capsulorrhaphy is one of the most critical steps during the process of open reduction of DDH. Inadequate capsulorrhaphy technique can increase the failure rate of open reduction procedures. This study presented the clinical and radiographic results of using a new capsulorrhaphy technique. METHODS: Between November 2005 and March 2018, 540 DDH in 462 patients were retrospectively reviewed. The mean age at surgery was 31 months. All patients underwent a modified capsulorrhaphy technique developed by the main author (with or without additional pelvic or femoral procedures). Postoperative patient assessment during the follow-up period was performed both clinically and radiologically. RESULTS: Follow-up period ranged between 36 months and 12 years. Based on the modified McKay score, good and excellent outcomes were obtained in 90.3%. Functional results were better in younger age (less than 39 mo). Both acetabular index and lateral center edge angle showed significant improvement at 3 years follow-ups. Proximal femoral growth disturbance (PFGD) was encountered in 92 hips. Classes 2 and 3 did not affect the functional results, whereas patients with PFGD classes 4 and 5 had fair to poor functional outcomes. There were 12 hips with redislocation. Revision was done using the same capsulorrhaphy technique. CONCLUSION: Using the index technique of capsulorrhaphy in DDH surgery is safe, reliable, and yields good functional and radiologic outcomes with a relatively low complication rate. LEVEL OF EVIDENCE: Level IV-therapeutic retrospective case series.

Trapped fourth ventricle: a rare complication in children after supratentorial CSF shunting.

PURPOSE: Trapped fourth ventricle (TFV) is a well-identified problem in hydrocephalic children. Patients with post-hemorrhagic hydrocephalus (PHH) are mostly affected. We tried to find out predisposing factors and describe clinical findings to early diagnose TFV and manage it. METHODS: We reviewed our database from 1991 to 2018 and included all patients with TFV who required surgery. We analyzed prematurity, cause of hydrocephalus, type of valve implanted, revision surgeries, modality of treatment of TFV, and their clinical examination and MRI imaging. RESULTS: We found 21 patients. Most of patients suffered from PHH (16/21), tumor (2/21), post-meningitis hydrocephalus (2/21), and congenital hydrocephalus (1/21). Seventeen patients were preterm. Seven patients suffered from a chronic overdrainage with slit ventricles in MRI. Thirteen patients showed symptoms denoting brain stem dysfunction; in 3 patients, TFV was asymptomatic and in 5 patients, we did not have available information regarding presenting symptoms due to missing documentation. An extra fourth ventricular catheter was the treatment of choice in 18/21 patients. One patient was treated by cranio-cervical decompression. Endoscopic aqueductoplasty with stenting was done in last 2 cases. CONCLUSION: Diagnosis of clinically symptomatic TFV and its treatment is a challenge in our practice of pediatric neurosurgery. PHH and prematurity are risk factors for the development of such complication. Both fourth ventricular shunting and endoscopic aqueductoplasty with stenting are effective in managing TFV. Microsurgical fourth ventriculostomy is not recommended due to its high failure rate. Early detection and intervention may help in avoiding fatal complication and improving the neurological function.

ETV in infancy and childhood below 2 years of age for treatment of hydrocephalus.

PURPOSE: Age and etiology play a crucial role in success of endoscopic third ventriculostomy (ETV) as a treatment of obstructive hydrocephalus. Outcome is worse in infants, and controversies still exist whether ETV is superior to shunt placement. We retrospectively analyzed 70 patients below 2 years from 4 different centers treated with ETV and assessed success. METHODS: Children < 2 years who received an ETV within 1994-2018 were included. Patients were classified according to age and etiology; < 3, 4-12, and 13-24 months, etiologically; aqueductal stenosis, post-hemorrhagic-hydrocephalus (PHH), tumor-related, fourth ventricle outflow obstruction, with Chiari-type II and following CSF infection. We investigated statistically the predictors for ETV success through computing Kaplan-Meier estimates using patient's follow-up time and time to ETV failure. RESULTS: We collected 70 patients. ETV success rate was 41.4%. The highest rate was in tumor-related hydrocephalus and fourth ventricle outlet obstruction (62.5%, 60%) and the lowest rate was in Chiari-type II and following infection (16.7%, 0%). The below 3 months age group showed relatively lower success rate (33.3%) in comparison to older groups which showed similar results (46.4%, 46.6%). Statistically, a previous VP shunt was a predictor for failure (p value < 0.05). CONCLUSION: Factors suggesting a high possibility of failure were age < 3 months and etiology such as Chiari-type II or following infection. Altered CSF dynamics in patients with PHH and under-developed arachnoid villi may play a role in ETV failure. We do not recommend ETV as first line in children < 3 months of age or in case of Chiari II or following infection.

Pericytes: Intrinsic Transportation Engineers of the CNS Microcirculation.

Pericytes in the brain are candidate regulators of microcirculatory blood flow because they are strategically positioned along the microvasculature, contain contractile proteins, respond rapidly to neuronal activation, and synchronize microvascular dynamics and neurovascular coupling within the capillary network. Analyses of mice with defects in pericyte generation demonstrate that pericytes are necessary for the formation of the blood-brain barrier, development of the glymphatic system, immune homeostasis, and white matter function. The development, identity, specialization, and progeny of different subtypes of pericytes, however, remain unclear. Pericytes perform brain-wide 'transportation engineering' functions in the capillary network, instructing, integrating, and coordinating signals within the cellular communicome in the neurovascular unit to efficiently distribute oxygen and nutrients ('goods and services') throughout the microvasculature ('transportation grid'). In this review, we identify emerging challenges in pericyte biology and shed light on potential pericyte-targeted therapeutic strategies.

Acute Correction and Plate Fixation for the Management of Severe Infantile Blount's Disease: Short-term Results.

PURPOSE: The purpose of this study is to evaluate the short-term results of lateral closing wedge osteotomy with medial hemiplateau elevation for the management of severe infantile Blount's disease. MATERIALS AND METHODS: In this prospective study, 11 cases of severe Blount's disease (Langenskiold stages five and six) were managed in the period between January 2017 and January 2020. Double osteotomy technique was applied, namely a metaphyseal closing wedge and a medial hemiplateau elevation, through a single midline incision. Fixation was achieved by a medial anatomical locked plate. Patients were evaluated clinically according to a modified version of paediatric outcomes data collection Instrument (PODCI) and radiologically by measuring the angle between the tibial and the femoral shaft, the mechanical axis deviation (MAD) and the angle of the medial tibial plateau (MTP) depression. RESULTS: The average follow-up period was 2 years. Healing of the osteotomies was achieved in all cases after the index operation within an average of 3 months. Based on our modification of the PODCI score, five cases had an excellent outcome, five were good, and one case ended with a fair outcome. No major complications were encountered in this study. CONCLUSION: The management of severe Blount's disease by acute correction using the aforementioned technique has been proven to achieve acceptable clinical and radiological outcomes without significant complications. LEVEL OF EVIDENCE: Level IV case series study. HOW TO CITE THIS ARTICLE: Nada AA, Hammad ME, Eltanahy AF, et al. Acute Correction and Plate Fixation for the Management of Severe Infantile Blount's Disease: Short-term Results. Strategies Trauma Limb Reconstr 2021;16(2):78-85.

Assessment of Blood Clot Composition by Spectral Optical Coherence Tomography: An In Vitro Study.

PURPOSE: Optical coherence tomography (OCT) has the potential for in vivo clot composition characterization in difficult mechanical embolectomy cases. We performed an in vitro study to determine the OCT characteristics of red blood cells (RBCs) and fibrin rich clots. MATERIALS AND METHODS: Analogues of 5 compositions of clots (5% to 95% RBCs from Group A to E) were created from human blood. The blood mixture was injected into the bifurcation of a 3D printed bifurcated silicone tube. The OPTISTM Integrated System (St. Jude Medical Inc.) was used to identify the magnitude of OCT signals from different compositions of clots. Martius Scarlett Blue trichrome (MSB) staining was performed to confirm the composition of RBCs and fibrin in each clot. RESULTS: Group A and B showed less signal attenuation (less than 30%) from its surface to the inside, which indicated high penetration (low-back scattering). Group C indicated intermediate signal attenuation (60%) from its surface to inside the clots, in which signals were found even at the periphery of the clot. Group D and E were superficially signal rich with more signal attenuation (more than 80%) from its surface to the inside indicating low penetration (high-back scattering). Signal-free shadowing was shown in 3 clots in Group E. MSB staining indicated color change (from red in fibrin-rich clots to yellow in RBC-rich clots). CONCLUSION: Different compositions of clots can be assessed using OCT. Fibrin-rich clots have homogeneous signals with high penetration, while RBC-rich clots can be recognized as superficially signal rich with low penetration.

PDGF-B Is Required for Development of the Glymphatic System.

The glymphatic system is a highly polarized cerebrospinal fluid (CSF) transport system that facilitates the clearance of neurotoxic molecules through a brain-wide network of perivascular pathways. Herein we have mapped the development of the glymphatic system in mice. Perivascular CSF transport first emerges in hippocampus in newborn mice, and a mature glymphatic system is established in the cortex at 2 weeks of age. Formation of astrocytic endfeet and polarized expression of aquaporin 4 (AQP4) consistently coincided with the appearance of perivascular CSF transport. Deficiency of platelet-derived growth factor B (PDGF-B) function in the PDGF retention motif knockout mouse line Pdgfbret/ret suppressed the development of the glymphatic system, whose functions remained suppressed in adulthood compared with wild-type mice. These experiments map the natural development of the glymphatic system in mice and define a critical role of PDGF-B in the development of perivascular CSF transport.