Highlights d The glymphatic system is first developed in the hippocampus d Insufficient PDGF-B signaling decreases AQP4 polarization to astrocyte vascular endfeet d Insufficient PDGF-B signaling impairs maturation of the glymphatic function
The complex and dynamic system of fluid flow through the perivascular and interstitial spaces of the central nervous system has new-found implications for neurological diseases. Cerebrospinal fluid movement throughout the CNS parenchyma is more dynamic than could be explained via passive diffusion mechanisms alone. Indeed, a semi-structured glial-lymphatic (glymphatic) system of astrocyte-supported extracellular perivascular channels serves to directionally channel extracellular fluid, clearing metabolites and peptides to optimize neurologic function. Clinical studies of the glymphatic network has 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 aging, neurodegenerative disease, and CNS injuries, as well as normal pressure hydrocephalus. Unlocking such pathophysiology could provide important avenues toward 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.
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.
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