RTL1/PEG11 imprinted in human and mouse brain mediates anxiety-like and social behaviors and regulates neuronal excitability in the locus coeruleus.

RTL1/PEG11, which has been associated with anxiety disorders, is a retrotransposon-derived imprinted gene in the placenta. However, imprinting patterns and functions of RTL1 in the brain have not been well-investigated. We found Rtl1 was paternally, but not maternally, expressed in brain stem, thalamus, and hypothalamus of mice, and imprinting status of RTL1 was maintained in human brain. Paternal Rtl1 knockout (Rtl1m+/p-) mice had higher neonatal death rates due to impaired suckling, and low body weights beginning on embryonic day 16.5. High paternal expression of Rtl1 was detected in the locus coeruleus (LC) and Rtl1m+/p- mice showed an increased delay in time of onset for action potentials and inward currents with decreased neuronal excitability of LC neurons. Importantly, Rtl1m+/p- mice exhibited behaviors associated with anxiety, depression, fear-related learning and memory, social dominance, and low locomotor activity. Taken together, our findings demonstrate RTL1 is imprinted in brain, mediates emotional and social behaviors, and regulates excitability in LC neurons.

Contemporary Management of Pediatric Brainstem Tumors.

Brain tumors are the second most common malignancy in childhood. Around 15-20% of pediatric brain tumors occur in the brainstem. The most common type of brainstem tumor are diffuse tumors in the ventral pons, whereas focal tumors tend to arise from the midbrain, medulla, and dorsal pons. Glioma is the most common pathological entity. Contemporary management consists of surgery, radiotherapy, chemotherapy, and other adjuvant treatment. Surgical options range from biopsy to radical excision. Biopsy can be performed for diagnostic and prognostic purposes, or in the setting of clinical trials, mainly for diffuse intrinsic pontine gliomas. For focal tumors, surgeons need to carefully balance clinical outcomes against possible neurological sequelae in order to achieve maximal safe resection. Radiotherapy is essential for control of high-grade tumors and may be applied to residual or recurrent low-grade tumors. Proton therapy may provide similar efficacy and less neurotoxicity in comparison to conventional photon therapy. Oncological treatment continues to evolve from conventional chemotherapy to targeted therapy, immunotherapy, and other novel treatment methods and holds great potential as adjuvant therapy for pediatric brainstem tumors.

Integration of immunohistochemistry, RNA sequencing, and multiplex ligation-dependent probe amplification for molecular classification of pediatric medulloblastoma.

BACKGROUND: Medulloblastoma (MB) is commonly classified into four molecular groups, that is, WNT, SHH, group 3, and group 4, for prognostic and therapeutic purposes. METHODS: Here we applied immunohistochemistry (IHC) and RNA sequencing (RNA-seq) for the molecular classification of MB, and utilized multiplex ligation-dependent probe amplification (MLPA) to determine chromosomal alterations and specific gene amplifications. RESULTS: We retrospectively enrolled 37 pediatric MB patients. Twenty-three had genomic material available for gene/RNA analysis. For IHC, ß-catenin, GAB1, and YAP were the biomarkers to segregate MB into three subgroups, WNT (1/23), SHH (5/23), and non-WNT/non-SHH (17/23). However, four cases (17.3%) were found to be misclassified after analysis by RNA-seq. The result of MLPA revealed two group 3 tumors carrying MYC amplification, and three SHH tumors harboring MYCN amplification. While IHC provided rapid subgroup stratification, it might result in incorrect subgrouping. Thus, validation of the IHC result with genomic data analysis by RNA-seq or other tools would be preferred. In addition, MLPA can detect important genetic alterations and is helpful for the identifications of high-risk patients. CONCLUSIONS: Our study revealed that integration of these diagnostic tools can provide a precise and timely classification of MB, optimizing an individualized, risk-directed postoperative adjuvant therapy for these patients. This workflow can be applied in a countrywide fashion to guide future clinical trials for patients with MB.

Abusive head trauma: current practice of investigation and management in Taiwan.

INTRODUCTION: Abusive head trauma (AHT) is a worldwide leading cause of fatal head injuries in children under 2 years. This study aims to present the development of child protection medical service in Taiwan in the past decade. MATERIALS AND METHODS: This study reviews the evolution of the pediatric protection network and the cross-system professional training in Taiwan from 2013 to 2022. The recommendations of Taiwan Pediatric Association on the prevention and management of AHT and the Medical Professionals Manual of Child Abuse and Neglect proposed by the Ministry of Health and Welfare were reviewed. RESULTS: Considering the impact of the high incidence of severe sequelae and the mortality caused by of AHT, 10 regional centers for child protection medical service were founded in Taiwan to identify, recognize, and properly manage cases of AHT, which is easily overlooked by the healthcare providers. The child protection network across the healthcare, social welfare administration, and judicial systems facilitate the early detection, management, and proper disposition of the children with AHT. CONCLUSION: An increasing of the incidence of AHT is expected after the setting up of the child protection network and the continuing cross-system professional trainings. There is more consensus of the diagnosis and management of AHT than before in Taiwan. However, there is no end to protecting children from AHT.

Long-term outcomes of moyamoya disease following indirect revascularization in middle adulthood: A prospective, quantitative study.

BACKGROUND/PURPOSE: Our previous study demonstrated that indirect revascularization is effective in the treatment of adult moyamoya patients. This prospective study aims to evaluate the long-term effectiveness of indirect revascularization in moyamoya patients in middle adulthood. METHODS: From January 2013 to June 2019, moyamoya patients more than 40 years of age underwent indirect revascularizations were studied. The hypoperfusion area of brains was revascularized. The cerebral angiography and time-to-peak (TTP) scoring (ranged 0-14) of the magnetic resonance perfusion study were used to evaluate the revascularization effect. RESULTS: During the study period, 50 consecutive adult moyamoya patients underwent indirect revascularization. Seventeen patients (27 cerebral hemispheres) more than 40 years of age were included. The mean age was 47.9 ± 6.4 years, and 13 patients were female. The pre-operative Suzuki stages were I, II, III, IV, V, and VI in 1, 1, 9, 13, 0, and 3 hemispheres, respectively. After a mean follow-up period of 52.5 ± 20.6 months, all patients had improvement or stabilization of their clinical conditions. Available post-operative angiography demonstrated Matsushima grading A in 18 of 20 hemispheres. The mean TTP score of all 27 hemispheres improved from 5.0 ± 3.3 pre-operatively to 12.0 ± 2.1 after surgery (p < 0.001). The post-operative mean TTP score of the 7 hemispheres without angiographic follow-up was 10.4 ± 1.8. One patient had persistent mild motor weakness after 56-month follow-up. Transient complications with full recovery occurred in 3 patients. CONCLUSION: Indirect revascularization is a safe method with satisfactory long-term results in moyamoya patient in middle adulthood.

Contemporary management of pediatric spinal tumors: a single institute's experience in Taiwan in the modern era.

INTRODUCTION: Pediatric spinal tumors are unique pathologies treated by pediatric neurosurgeons. Special attention is required for the preservation of neural function and bony alignment. We reported our experience in the management of these challenging lesions. METHODS: A total of 75 pediatric patients with spinal tumors treated at the National Taiwan University Hospital from 1998 to 2018 were identified retrospectively. Clinical data, radiographic image, and pathological report were reviewed for analysis. RESULTS: There were 37 females and 38 males. The median age was 9 years. Thirty-eight tumors (50.6%) were extradural, 20 (26.7%) intradural extramedullary, and 17 (22.6%) intramedullary. The most common pathologies were glioma, ependymoma, and neuroblastoma. The rate of total and subtotal resection was 45.3% and 21.3%. Thirty-four patients (45.3%) required post-operative adjuvant therapy. Eight patients (10.6%) with spinal deformity had simultaneous tumor excision and spinal fusion surgery. Additional six (8%) patients had subsequent spinal fixation and fusion for deformity after primary tumor operation. Eighty-four percent of patients were ambulatory 3 years after operation. For patients with intradural extramedullary and intramedullary tumors, worse survival outcome was associated with tumor derived from CSF seeding and cranial involvement of spinal tumor, while poorer functional outcome was correlated with cranial involvement and adjuvant therapy with chemotherapy or radiotherapy. CONCLUSIONS: Pediatric spinal tumor surgery carries low surgical morbidity and mortality under current standard of neurosurgical practice. Post-operative adjuvant therapy is required for nearly half of the cases. Spinal deformity requires special attention and sometimes surgical correction. Contemporary management of pediatric spinal tumors enables effective ablation of the lesion and delivers favorable outcome for the majority of patients.

Postoperative change of neuropsychological function after indirect revascularization in childhood moyamoya disease: a correlation with cerebral perfusion study.

PURPOSE: The relationships between postoperative functional improvement in various cognitive domains and regional hemodynamic change have not been sufficiently studied in childhood moyamoya disease (MMD). The present study aimed to examine the cognitive benefit of indirect revascularization, the underlying biological mechanism, and factors affecting surgical outcome in childhood MMD. METHODS: Twenty-three patients with MMD aged under 20 years received neuropsychological examinations before and after indirect revascularization surgery, evaluating intellectual function, verbal and visual memory, and executive function. Among them, 13 patients had magnetic resonance perfusion (MRP) studies, in which regional cerebral perfusion was rated. RESULTS: Postoperative improvement was observed in verbal memory performances (p = 0.02-0.03) and in cerebral perfusion at all 26 cerebral hemispheres (p = 0.003-0.005), especially in the middle cerebral artery (MCA) territories (p = 0.001-0.003). Hemodynamic improvement in the left MCA territories was significantly correlated with improvement of both verbal new learning (p = 0.01) and intellectual function (p = 0.004). Postoperative cognitive improvement of immediate recall and verbal intellectual function was associated with female sex (r = - 0.42) and symptom duration (p = - 0.03), respectively. Hemodynamic improvement in the MCA territories was related to longer follow-up intervals (p = 0.02). CONCLUSION: The findings revealed that the selective postoperative cognitive improvement was associated with increased regional perfusion in the MCA territories, and indicate the importance of early intervention and the potential of indirect revascularization regarding long-term outcome.

The state of neurosurgical training and education in East Asia: analysis and strategy development for this frontier of the world.

OBJECTIVE: The authors, who are from Indonesia, Japan, Malaysia, the Philippines, and Taiwan, sought to illustrate the processes of training neurosurgeons in their respective settings by presenting data and analyses of the current state of neurosurgical education across the East Asian region. METHODS: The authors obtained quantitative data as key indicators of the neurosurgical workforce from each country. Qualitative data analysis was also done to provide a description of the current state of neurosurgical training and education in the region. A strengths, weaknesses, opportunities, and threats (SWOT) analysis was also done to identify strategies for improvement. RESULTS: The number of neurosurgeons in each country is as follows: 370 in Indonesia, 10,014 in Japan, 152 in Malaysia, 134 in the Philippines, and 639 in Taiwan. With a large neurosurgical workforce, the high-income countries Japan and Taiwan have relatively high neurosurgeon to population ratios of 1 per 13,000 and 1 per 37,000, respectively. In contrast, the low- to middle-income countries Indonesia, Malaysia, and the Philippines have low neurosurgeon to population ratios of 1 per 731,000, 1 per 210,000, and 1 per 807,000, respectively. In terms of the number of training centers, Japan has 857, Taiwan 30, Indonesia 7, Malaysia 5, and the Philippines 10. In terms of the number of neurosurgical residents, Japan has 1000, Taiwan 170, Indonesia 199, Malaysia 53, and the Philippines 51. The average number of yearly additions to the neurosurgical workforce is as follows: Japan 180, Taiwan 27, Indonesia 10, Malaysia 4, and the Philippines 3. The different countries included in this report have many similarities and differences in their models and systems of neurosurgical education. Certain important strategies have been formulated in order for the system to be responsive to the needs of the catchment population: 1) establishment of a robust network of international collaboration for reciprocal certification, skills sharing, and subspecialty training; 2) incorporation of in-service residency and fellowship training within the framework of improving access to neurosurgical care; and 3) strengthening health systems, increasing funding, and developing related policies for infrastructure development. CONCLUSIONS: The varied situations of neurosurgical education in the East Asian region require strategies that take into account the different contexts in which programs are structured. Improving the education of current and future neurosurgeons becomes an important consideration in addressing the health inequalities in terms of access and quality of care afflicting the growing population in this region of the world.

The role of sacral laminoplasty in the management of spina bifida and sacral cystic lesions: case series.

OBJECTIVE: Although laminae are not viewed as essential structures for spinal integrity, in the sacrum the anatomical weakness and gravity makes it a vulnerable area for CSF accumulation and expansion. The congenital or postoperative defects of sacral laminae, such as in patients with spina bifida, make this area more susceptible to forming progressive dural ectasia, pseudomeningocele, or expansile arachnoid cyst (Tarlov cyst). In addition, adhesions between the dura and surrounding soft tissue after laminectomy can cause some local symptoms, which are difficult to relieve. The authors propose that sacral laminoplasty with titanium mesh can provide a rigid support and barrier to resolve these sacral lesions and local symptoms. METHODS: From January 2016 to December 2017, patients with progressive CSF-containing lesions in the sacral area and defective sacral laminae were included in the study. After repair of the lesion, the authors performed sacral laminoplasty with titanium mesh in each patient. Subsequently, the soft tissue and skin were closed primarily. RESULTS: A total of 6 patients were included. Four patients with repaired myelomeningocele had progressive dural ectasia. One patient with lipomyelomeningocele previously underwent detethering surgery and developed postoperative pseudomeningocele. One patient had a symptomatic Tarlov cyst. Four of these 6 cases presented with low-back pain and local tenderness. During follow-up, ranging from 13 to 37 months, all 6 patients experienced no recurrence of dural ectasia or pseudomeningocele and were free from local symptoms. CONCLUSIONS: Sacral laminoplasty with titanium mesh is a safe and effective procedure for treating progressive sacral dural ectasia and refractory pseudomeningocele, preventing CSF leakage as well as relieving local symptoms that may occur years after previous surgery for spina bifida.

Modified concentric craniotomy for the removal of a huge calvarial metastatic tumor: technical note.

BACKGROUND: It is challenging for neurosurgeons to remove huge tumors involving the skull that may possibly invade the dura or intracranial neural tissue. In this situation, excision of the tumor may cause profound blood loss, unexpected opening of the dura, or neurological injury. We describe a technique of craniotomy in a pediatric patient to avoid surgical complications. METHODS: A 15-year-old boy had a huge metastatic calvarial Ewing's sarcoma. We removed the tumor successfully with modified concentric craniotomy. First, two oval burr holes are made on both sides of the tumor. The inner craniotomy uses the internal margin of the oval holes, while the outer cut uses the outer margins. The skull bone in between the two craniotomies is removed easily in two pieces and the dura surrounding the tumor can be exposed early in the procedure. In this way, the huge skull tumor can be removed en bloc under direct vision to avoid unwanted complications. Minimal blood and bone loss can be achieved. RESULTS: Blood transfusion was not necessary during the surgery. The patient did not have new neurological symptoms and signs after surgery. CONCLUSIONS: The goal of the modified concentric craniotomy is to develop an accessible margin of the dura surrounding the bulky tumor in the early phase of surgery. Blood and bone loss can be reduced significantly.

Acquired Chiari malformation type I associated with a supratentorial fistulous arteriovenous malformation: a case report.

A case of acquired Chiari malformation type I with frontal fistulous arteriovenous malformation (AVM) is presented, and the pathophysiology is discussed. The tonsillar herniation and hydrocephalus both resolved after AVM was excised. This case provides some insight into the complex hemodynamic change exerted by the fistulous AVM and the mechanism of the development of acquired Chiari malformation type I.

Epidemiology of moyamoya disease in Taiwan: a nationwide population-based study.

BACKGROUND AND PURPOSE: Previous studies have shown regional and temporal variations in epidemiological features of moyamoya disease, but population-based studies in regions other than Japan are limited. We investigated the incidence and patients characteristics of moyamoya disease during 12 years in Taiwan using claims databases of a universal health insurance system. METHODS: From the inpatient databases of the Taiwan National Health Insurance program, we identified subjects who had an initial hospitalization with moyamoya disease and had been underwent cerebral angiography as incidence cases during 2000 to 2011. The incidence and the patient characteristics were described by age and time periods of the hospitalization. RESULTS: During the 12-year period, 422 patients were identified, representing an annual incidence of 0.15 per 100,000 person-years. Adults exhibited an upward trend in incidence with an incidence rate ratio of 1.74 (95% confidence interval [1.17-2.58]) in years 2010 to 2011 comparing with years 2000 to 2001. However, children had a decreased incidence except a slightly increase in the last 2 years. Compared with patients hospitalized during 2000 to 2005, patients identified during 2006 to 2011 had greater women-to-men ratio (1.7 versus 1.1, P=0.048). Children were more likely to have comorbid epilepsy than were adult patients (25.0% versus 3.4%, P=0.002). Hemorrhagic stroke was rare among pediatric patients but presented more frequently in adults. However, ischemic stroke was more prevalent in both groups. CONCLUSIONS: The incidence of moyamoya disease has increased in adults but not in children from 2000 to 2011 in Taiwan. Sex ratio and comorbid conditions differed by age and study period.

Selective neuropsychological impairments and related clinical factors in children with moyamoya disease of the transient ischemic attack type.

PURPOSE: Moyamoya disease is characterized by progressive narrowing of bilateral internal carotid arteries. Neuropsychological impairments are suspected due to frequent involvement of the frontotemporal areas. The present study thus aimed to investigate the pattern of neuropsychological function in children diagnosed with moyamoya disease. METHODS: Thirteen children with moyamoya disease of the transient ischemic attack type received standardized neuropsychological tests that evaluate general intellectual function, verbal comprehension, perceptual organization, working memory, processing speed, episodic memory, category fluency and visuospatial function. Related clinical factors were also analyzed. RESULTS: The results showed single-domain cognitive impairment in around 15 % of patients and multiple-domain cognitive impairments in 23 % of patients. Selective impairments of episodic memory and processing speed were especially noted in those with younger age of onset and prolonged symptom duration. CONCLUSIONS: Neuropsychological impairments are not infrequent in children with moyamoya disease despite normal general intellectual functioning. The pattern of cognitive dysfunction is often associated with lesions in frontotemporal areas. Early detection and intervention shall be considered regarding cognitive outcome in pediatric group.

Neuroimaging and electroencephalographic changes after vagus nerve stimulation in a boy with medically intractable myoclonic astatic epilepsy.

Myoclonic astatic epilepsy (MAE) is characterized by multiple seizure types, which are often refractory. Although vagus nerve stimulation (VNS) is an alternative treatment for medically intractable seizures, its exact mechanism of action remains unclear. Herein, we report the case of a 4-year-old boy with intractable MAE who has been in a seizure-free status for 2 years and 3 months since 6 months after the implantation of a vagus nerve stimulator (Model 103, Cyberonics, Inc., Houston, TX). Various test results 6 months after VNS were compared with those before VNS. Results of an electroencephalograph revealed disappearance of epileptiform discharges and an increased beta-gamma spectrum rhythm. The brain diffusion-tensor imaging showed an increased ratio of fraction anisotropy in the right fimbria-fornix, indicating improved diffusion of the white matter tract, and (18)F-fluorodeoxyglucose positron emission tomography revealed globally improved cerebral glucose metabolism. His cognitive and social-emotional performances also improved at 2 years after VNS. To the best of our knowledge, this is the first report to describe the effects of VNS on fimbria-fornix and glucose metabolism in MAE.

Microcirculatory Impairment and Cerebral Injury in Hydrocephalus and the Effects of Cerebrospinal Fluid Diversion.

BACKGROUND AND OBJECTIVES: Hydrocephalus is characterized by progressive enlargement of cerebral ventricles, resulting in impaired microvasculature and cerebral hypoperfusion. This study aimed to demonstrate the microvascular changes in hydrocephalic rats and the effects of cerebrospinal fluid (CSF) release on cerebral blood flow (CBF). METHODS: On postnatal day 21 (P21), male Wistar rats were intracisternally injected with either a kaolin suspension or saline. On P47, Evan's ratio (ER) was measured using MRI. On P49, the arteriolar diameter and vascular density of the pia were quantified using a capillary video microscope. The CBF was measured using laser Doppler flowmetry. The expressions of NeuN and glial fibrillary acidic protein determined by immunochemical staining were correlated with the ER. The CBF and rotarod test performance were recorded before and after CSF release. The expressions of 4-hydroxynonenal (4-HNE) and c-caspase-3 were studied on P56. RESULTS: Ventriculomegaly was induced to varying degrees, resulting in the stretching and abnormal narrowing of pial arterioles, which regressed with increasing ER. Quantitative analysis revealed significant decreases in the arteriolar diameter and vascular density in the hydrocephalic group compared with those in the control group. In addition, the CBF in the hydrocephalic group decreased to 30%-50% of that in the control group. In hydrocephalus, the neurons appear distorted, and the expression of 4-HNE and reactive astrogliosis increase in the cortex. After CSF was released, improvements in the CBF and rotarod test performance were inversely associated with the ER. In addition, the levels of 4-HNE and c-caspase-3 were further elevated. CONCLUSION: Rapid ventricular dilatation is associated with severe microvascular distortion, vascular regression, cortical hypoperfusion, and cellular changes that impair the recovery of CBF and motor function after CSF release. Moreover, CSF release may induce reperfusion injury. This pathophysiology should be taken into account when treating hydrocephalus.

Clinical characteristics of central diabetes insipidus in Taiwanese children.

BACKGROUND/PURPOSE: Data on the clinical features of children with central diabetes insipidus (CDI) are lacking in Taiwan. This study investigated the clinical manifestations and etiology of CDI in Taiwanese children. METHODS: From 1983 to 2012, 62 children with permanent diabetes insipidus were enrolled in the study. They were diagnosed at the Department of Pediatrics of National Taiwan University Hospital. Their medical records were thoroughly reviewed and their clinical symptoms and signs, laboratory data, and etiologies were analyzed. RESULTS: The patients' median age at diagnosis was 10 years and the median interval between initial manifestations and diagnosis was 0.5 years. The most common symptoms and signs were polyuria, polydipsia, nocturia, and growth retardation. Most patients had low urine osmolality and elevated plasma osmolality on diagnosis. Absence of a posterior pituitary hyperintense signal and thickening of the pituitary stalk were common findings on magnetic resonance imaging. Approximately 80% of the patients had anterior pituitary hormone deficiency and all patients had growth hormone deficiency. Approximately 60% of patients had intracranial lesions, the most common causes of which were germ cell tumor and Langerhans cell histiocytosis. Two patients were initially believed to have idiopathic CDI but intracranial lesions were detected during the follow-up period. CONCLUSION: Because a delayed diagnosis of CDI is common in Taiwanese children, a high index of suspicion is important. The underlying etiology of CDI in children may not initially be obvious. Long-term surveillance is therefore necessary, especially for the early detection of evolving treatable intracranial lesions.

Mir125b-2 imprinted in human but not mouse brain regulates hippocampal function and circuit in mice.

Genomic imprinting predominantly occurs in the placenta and brain. Few imprinted microRNAs have been identified in the brain, and their functional roles in the brain are not clear. Here we show paternal, but not maternal, expression of MIR125B2 in human but not mouse brain. Moreover, Mir125b-2m-/p- mice showed impaired learning and memory, and anxiety, whose functions were hippocampus-dependent. Hippocampal granule cells from Mir125b-2m-/p- mice displayed increased neuronal excitability, increased excitatory synaptic transmission, and decreased inhibitory synaptic transmission. Glutamate ionotropic receptor NMDA type subunit 2A (Grin2a), a key regulator of synaptic plasticity, was physically bound by miR-125b-2 and upregulated in the hippocampus of Mir125b-2m-/p- mice. Taken together, our findings demonstrate MIR125B2 imprinted in human but not mouse brain, mediated learning, memory, and anxiety, regulated excitability and synaptic transmission in hippocampal granule cells, and affected hippocampal expression of Grin2a. Our work provides functional mechanisms of a species-specific imprinted microRNA in the brain.

Antisiphon device: A review of existing mechanisms and clinical applications to prevent overdrainage in shunted hydrocephalic patients.

Overdrainage of cerebrospinal fluid is one of the most notorious complications after ventriculoperitoneal shunt implantation. Siphon effect plays a major role in the development of overdrainage. Various overdrainage-preventing devices have been invented to counteract the siphon effect. Though some of the devices are designed to reduce the flow instead of providing antisiphoning effect, they are generally called antisiphon devices (ASDs). The basics of siphoning, the mechanisms and physical properties of currently available devices are described in this article. The clinical efficacy, shunt survival, and considerations on patient factors are also discussed. There are three kinds of ASD design, diaphragm, gravitational, and flow reducing devices. Flow reducing ASD is always open and the flow it controls is relatively stable. On the other hand, it may not provide sufficient flow in nocturnal intracranial pressure elevations. Diaphragm and gravitational devices are sensitive to the position of the patients. Diaphragm device is sensitive to the external pressure and the relative position of the device to the mastoid process. The gravitational device is sensitive to the angle between the axis of the device and the head. Many studies showed encouraging results with gravitational devices. Studies regarding diaphragm devices either showed better or similar outcomes comparing to differential pressure valves. Clinical studies regarding flow-reducing devices and head-to-head comparison between different mechanisms are warranted. This review aims to provide a useful reference for clinical practice of hydrocephalus.

A Proposed Algorithm for Managing Cerebral Proliferative Angiopathy.

OBJECTIVE: Cerebral proliferative angiopathy (CPA) is a rare disease, characterized by a large vascular nidus, diffuse angiogenesis, and intermingled normal brain tissue. Conservative treatment, endovascular intervention, indirect revascularization, and radiotherapy have been applied to treat this disease. However, some cases deteriorate even after non-conservative treatment, and there has been no standard of treatment for this disease so far. In order to build a better treatment strategy, we review literature, present our case and propose an algorithm for managing CPA. METHODS: Following the PRISMA principle, we systemically reviewed literature discussing CPA. A case successfully managed with multi-modal treatment is also illustrated. RESULTS: A total of 23 articles with 74 cases of CPA were found. Thirty-three patients received single-modal management. These 33 cases include 24 receiving endovascular intervention, 7 receiving indirect revascularization, and 2 receiving radiotherapy. Three of the 33 patients deteriorated clinically, and 1 expired. We present a 6-year-old boy with left hemispheric CPA receiving indirect revascularization, followed by 2 consecutive courses of stereotactic radiosurgery targeting arteriovenous shunts in the left basal ganglia and arteriovenous shunts around the olfactory groove. In the follow-up period of more than 4 years, good collateral formation, improved perilesional perfusion, CPA shrinkage, and symptom relief were all achieved. CONCLUSIONS: Based on our literature review and case, we propose an algorithm for the management of CPA and emphasize that multi-modal treatment is necessary for most CPA cases.

Combination of indirect revascularization and endothelial progenitor cell transplantation improved cerebral perfusion and ameliorated tauopathy in a rat model of bilateral ICA ligation.

OBJECTIVE: Endothelial progenitor cells (EPCs) contribute to the recovery of neurological function after ischemic stroke. Indirect revascularization has exhibited promising effects in the treatment of cerebral ischemia related to moyamoya disease and intracranial atherosclerotic disease. The role of EPCs in augmenting the revascularization effect is not clear. In this study, we investigated the therapeutic effects of indirect revascularization combined with EPC transplantation in rats with chronic cerebral ischemia. METHODS: Chronic cerebral ischemia was induced by bilateral internal carotid artery ligation (BICAL) in rats, and indirect revascularization by encephalo-myo-synangiosis (EMS) was performed 1 week later. During the EMS procedure, intramuscular injection of EPCs and the addition of stromal cell-derived factor 1 (SDF-1), and AMD3100, an SDF-1 inhibitor, were undertaken, respectively, to investigate their effects on indirect revascularization. Two weeks later, the cortical microcirculation, neuronal damage, and functional outcome were evaluated according to the microvasculature density and partial pressure of brain tissue oxygen (PbtO2), regional blood flow, expression of phosphorylated Tau (pTau), TUNEL staining and the rotarod performance test, respectively. RESULTS: The cortical microcirculation, according to PbtO2 and regional blood flow, was impaired 3 weeks after BICAL. These impairments were improved by the EMS procedure. The regional blood flow was further increased by the addition of SDF-1 and decreased by the addition of AMD3100. Intramuscular injection of EPCs further increased the regional blood flow as compared with the EMS group. The rotarod test results showed that the functional outcome was best in the EMS combined with EPC injection group. Western blot analysis showed that the EMS combined with EPC treatment group had significantly decreased expressions of phosphorylated Tau and phosphorylated glycogen synthase kinase 3 beta (Y216 of GSK-3ß). pTau and TUNEL-positive cells were markedly increased at 3 weeks after BICAL induction. Furthermore, the groups treated with EMS combined with SDF-1 or EPCs exhibited marked decreases in the pTau expression and TUNEL-positive cells, whereas AMD3100 treatment increased TUNEL-positive cells. CONCLUSION: The results of this study suggested that indirect revascularization ameliorated the cerebral ischemic changes. EPCs played a key role in augmenting the effect of indirect revascularization in the treatment of chronic cerebral ischemia.