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In India, adult neurosurgeons are required to care for children regularly because the concept of dedicated pediatric specialty care is not yet entirely established in the subcontinent. Likewise, pediatric neurosurgeons do not exclusively offer their services to the young, but they also provide care to adult patients with neurosurgical disorders. This creates a medical system where the transition between specialties is not often a formal and recognized aspect of neurosurgical care because most neurosurgeons provide care for patients of all ages. Additionally, there are very few teams geared toward caring for conditions in children that merit lifelong medical support, with spina bifida (SB) being one of them. Since there are no focused or structured pediatric programs on a large scale, developing a multidisciplinary clinic for adults becomes challenging. A pragmatic approach using technology-based education, supported by an organized system or a coordinator, may be a new strategy. A new system utilizing telemedicine and smartphones for established patients maybe an alternative option for SB children in India. During virtual video conferences, an established patient may benefit from multispecialty care and education toward a smooth transition that avoids significant issues with time, transportation, or financial constraints. Achieving a seamless transition among allied specialists from the pediatric to adult systems is a utopia. The current system in the subcontinent may be improved, with an opportunity to develop smooth transition care between coordinated specialists (who simultaneously treat children and adults). Learning from various global SB management styles, the Indian transition situation may offer another model in the near future.

Background: The epidemiology of traumatic brain injury (TBI) is unclear - it is estimated to affect 27-69 million individuals yearly with the bulk of the TBI burden in low-to-middle income countries (LMICs). Research has highlighted significant between-hospital variability in TBI outcomes following emergency surgery, but the overall incidence and epidemiology of TBI remains unclear. To address this need, we established the Global Epidemiology and Outcomes following Traumatic Brain Injury (GEO-TBI) registry, enabling recording of all TBI cases requiring admission irrespective of surgical treatment., Objective: The GEO-TBI: Incidence study aims to describe TBI epidemiology and outcomes according to development indices, and to highlight best practices to facilitate further comparative research., Design: Multi-centre, international, registry-based, prospective cohort study., Subjects: Any unit managing TBI and participating in the GEO-TBI registry will be eligible to join the study. Each unit will select a 90-day study period. All TBI patients meeting the registry inclusion criteria (neurosurgical/ICU admission or neurosurgical operation) during the selected study period will be included in the GEO-TBI: Incidence., Methods: All units will form a study team, that will gain local approval, identify eligible patients and input data. Data will be collected via the secure registry platform and validated after collection. Identifiers may be collected if required for local utility in accordance with the GEO-TBI protocol., Data: Data related to initial presentation, interventions and short-term outcomes will be collected in line with the GEO-TBI core dataset, developed following consensus from an iterative survey and feedback process. Patient demographics, injury details, timing and nature of interventions and post-injury care will be collected alongside associated complications. The primary outcome measures for the study will be the Glasgow Outcome at Discharge Scale (GODS) and 14-day mortality. Secondary outcome measures will be mortality and extended Glasgow Outcome Scale (GOSE) at the most recent follow-up timepoint., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Joannides A et al.)

Importance: India has a disproportionately high prevalence of neural tube defects, including spina bifida and anencephaly (SBA), causing a high number of stillbirths, elective pregnancy terminations, and child mortality; India contributes a large proportion of the global burden of SBA. Thirty years after folic acid was shown to be effective in reducing SBA prevalence, only about one-quarter of such births are prevented globally through cereal grain fortification., Objective: To determine the association of folic acid-fortified iodized salt with serum folate concentrations among nonpregnant and nonlactating women of reproductive age., Design, Setting, and Participants: This nonrandomized controlled trial using a preintervention and postintervention design was conducted in 4 rural villages in Southern India from July 1 to November 30, 2022. All households in the villages agreed to participate in the study. Preintervention and postintervention serum folate levels were analyzed among study participants at baseline and after 4 months, respectively., Intervention: Consumption of approximately 300 µg/d of folic acid using double fortified salt (folic acid plus iodine). Median serum folate concentrations were assessed at baseline and 4 months., Main Outcomes and Measures: Change in median serum folate levels between baseline and study end point as the primary outcome of the study., Results: A total of 83 nonpregnant nonlactating women aged 20 to 44 years (mean [SD] age, 30.9 [5.1] years) were eligible for the study and provided serum samples for analysis at baseline and the end point of the intervention. The median serum folate concentration increased from 14.6 (IQR, 11.2-20.6) nmol/L at baseline to 54.4 (IQR, 43.5-54.4) nmol/L at end of study, a 3.7-fold increase from baseline to study end point. Two-tailed Wilcoxon signed rank test showed the median difference in preintervention and postintervention serum folate concentrations to be highly significant (P < .001). The participants found the salt acceptable in color and taste., Conclusions and Relevance: Use of folic acid-fortified iodized salt was associated with increased serum folate concentrations in women of reproductive age. This novel evidence can inform public health policy to accelerate SBA prevention., Trial Registration: ClinicalTrials.gov Identifier: NCT06174883.

Background and Objectives: Global disparity exists in the demographics, pathology, management, and outcomes of surgically treated traumatic brain injury (TBI). However, the factors underlying these differences, including intervention effectiveness, remain unclear. Establishing a more accurate global picture of the burden of TBI represents a challenging task requiring systematic and ongoing data collection of patients with TBI across all management modalities. The objective of this study was to establish a global registry that would enable local service benchmarking against a global standard, identification of unmet need in TBI management, and its evidence-based prioritization in policymaking., Methods: The registry was developed in an iterative consensus-based manner by a panel of neurotrauma professionals. Proposed registry objectives, structure, and data points were established in 2 international multidisciplinary neurotrauma meetings, after which a survey consisting of the same data points was circulated within the global neurotrauma community. The survey results were disseminated in a final meeting to reach a consensus on the most pertinent registry variables., Results: A total of 156 professionals from 53 countries, including both high-income countries and low- and middle-income countries, responded to the survey. The final consensus-based registry includes patients with TBI who required neurosurgical admission, a neurosurgical procedure, or a critical care admission. The data set comprised clinically pertinent information on demographics, injury characteristics, imaging, treatments, and short-term outcomes. Based on the consensus, the Global Epidemiology and Outcomes following Traumatic Brain Injury (GEO-TBI) registry was established., Conclusion: The GEO-TBI registry will enable high-quality data collection, clinical auditing, and research activity, and it is supported by the World Federation of Neurosurgical Societies and the National Institute of Health Research Global Health Program. The GEO-TBI registry ( https://geotbi.org ) is now open for participant site recruitment. Any center involved in TBI management is welcome to join the collaboration to access the registry., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Chiari I malformation (CIM) is characterized by descent of the cerebellar tonsils through the foramen magnum, potentially causing symptoms from compression or obstruction of the flow of cerebrospinal fluid. Diagnosis and treatment of CIM is varied, and guidelines produced through systematic review may be helpful for clinicians., Objective: To perform a systematic review of the medical literature to answer specific questions on the diagnosis and treatment of CIM., Methods: PubMed and Embase were queried between 1946 and January 23, 2021, using the search strategies provided in Appendix I of the full guidelines., Results: The literature search yielded 567 abstracts, of which 151 were selected for full-text review, 109 were then rejected for not meeting the inclusion criteria or for being off-topic, and 42 were included in this systematic review., Conclusion: Three Grade C recommendations were made based on Level III evidence. The full guidelines can be seen online at https://www.cns.org/guidelines/browse-guidelines-detail/1-imaging ., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Chiari malformation type I (CIM) diagnoses have increased in recent years. Controversy regarding the best operative management prompted a review of the literature to offer guidance on surgical interventions., Objective: To assess the literature to determine (1) whether posterior fossa decompression or posterior fossa decompression with duraplasty is more effective in preoperative symptom resolution; (2) whether there is benefit from cerebellar tonsillar resection/reduction; (3) the role of intraoperative neuromonitoring; (4) in patients with a syrinx, how long should a syrinx be observed for improvement before additional surgery is performed; and 5) what is the optimal duration of follow-up care after preoperative symptom resolution., Methods: A systematic review was performed using the National Library of Medicine/PubMed and Embase databases for studies on CIM in children and adults. The most appropriate surgical interventions, the use of neuromonitoring, and clinical improvement during follow-up were reviewed for studies published between 1946 and January 23, 2021., Results: A total of 80 studies met inclusion criteria. Posterior fossa decompression with or without duraplasty or cerebellar tonsil reduction all appeared to show some benefit for symptom relief and syrinx reduction. There was insufficient evidence to determine whether duraplasty or cerebellar tonsil reduction was needed for specific patient groups. There was no strong correlation between symptom relief and syringomyelia resolution. Many surgeons follow patients for 6-12 months before considering reoperation for persistent syringomyelia. No benefit or harm was seen with the use of neuromonitoring., Conclusion: This evidence-based clinical guidelines for the treatment of CIM provide 1 Class II and 4 Class III recommendations. In patients with CIM with or without syringomyelia, treatment options include bone decompression with or without duraplasty or cerebellar tonsil reduction. Improved syrinx resolution may potentially be seen with dural patch grafting. Symptom resolution and syrinx resolution did not correlate directly. Reoperation for a persistent syrinx was potentially beneficial if the syrinx had not improved 6 to 12 months after the initial operation. The full guidelines can be seen online at https://www.cns.org/guidelines/browse-guidelines-detail/3-surgical-interventions ., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background: Chiari I malformation (CIM) is characterized by descent of the cerebellar tonsils through the foramen magnum, potentially causing symptoms from compression or obstruction of the flow of cerebrospinal fluid. Diagnosis and treatment of CIM is varied, and guidelines produced through systematic review may be helpful for clinicians., Objective: To perform a systematic review of the medical literature to answer specific questions on the diagnosis and treatment of CIM., Methods: PubMed and Embase were queried between 1946 and January 23, 2021, using the search strategies provided in Appendix I of the full guidelines., Results: The literature search yielded 430 abstracts, of which 79 were selected for full-text review, 44 were then rejected for not meeting the inclusion criteria or for being off-topic, and 35 were included in this systematic review., Conclusion: Four Grade C recommendations were made based on Class III evidence, and 1 question had insufficient evidence. The full guidelines can be seen online at https://www.cns.org/guidelines/browse-guidelines-detail/2-symptoms ., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

Background and Objective: About 14 million people will likely suffer a traumatic brain injury (TBI) per year by 2050 in sub-Saharan Africa. Studying TBI characteristics and their relation to outcomes can identify initiatives to improve TBI prevention and care. The objective of this study was to define the features and outcomes of TBI patients seen over a 1-year period in a level-I trauma centre in Cameroon. Materials and Methods: Data on demographics, causes, clinical aspects, and discharge status were collected over a period of 12 months. The Glasgow Outcome Scale-Extended (GOSE) and the Quality-of-Life Questionnaire after Brain Injury (QoLIBRI) were used to evaluate outcomes six months after TBI. Comparisons between two categorical variables were done using Pearson's chi-square test. Results: A total of 160 TBI patients participated in the study. The age group 15-45 years was most represented (78%). Males were more affected (90%). A low educational level was seen in 122 (76%) cases. Road traffic incidents (RTI) (85%), assaults (7.5%), and falls (2.5%) were the main causes of TBI, with professional bike riders being frequently involved (27%). Only 15 patients were transported to the hospital by ambulance, and 14 of these were from a referring hospital. CT-imaging was performed in 78% of cases, and intracranial traumatic abnormalities were identified in 64% of cases. Financial constraints (93%) was the main reason for not performing a CT scan. Forty-six (33%) patients were discharged against medical advice (DAMA) due to financial constraints. Mortality was 14% (22/160) and high in patients with severe TBI (46%). DAMA had poor outcomes with QoLIBRI. Only four patients received post-injury physical therapy services. Conclusions: TBI in Cameroon mainly results from RTIs and commonly affects young adult males. Lack of pre-hospital care, financial constraints limiting both CT scanning and medical care, and a lack of acute physiotherapy services likely influenced care and outcomes adversely.

Introduction: Globally, spina bifida (SB) occurs more often in low- and middle-income countries, where the healthcare demands are often quite challenging. Several social/societal issues and/or lack of government support makes for incomplete SB management in many areas. Clearly, neurosurgeons should be knowledgeable about initial closure techniques and the basics of SB management, but must also advocate for the patients outside our immediate scope of care., Methods: Recently, the Comprehensive Policy Recommendations for the Management of Spina Bifida and Hydrocephalus in Low- and Middle-Income Countries (CHYSPR) and the Intersectoral Global Action Plan on Epilepsy and other Neurological Disorders (IGAP) publications emphasized the need for a more unified approach to SB care. Although both documents discuss other neurological conditions, they support SB as a congenital malformation needing attention., Results: We identified several similarities for comprehensive SB care in these approaches - including education, governance, advocacy, and the need for continuum of care. Prevention was recognized as the most important aspect for SB going forward. A significant return of investment was noted, and both documents recommend more active neurosurgical involvement (i.e., folic acid fortification)., Conclusion: A new call for holistic and comprehensive care for SB management is recognized. Neurosurgeons are called upon to use solid science to educate governments and actively participate to advocate for better care and most importantly, prevention. Folic acid fortification schemes are mandatory and neurosurgeons should advocate for global strategies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://doi.org/10.1016/j.wneu.2023.02.013. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal., (Copyright © 2023 Elsevier Inc. All rights reserved.)

India has one of the highest TBI burdens due to road traffic accidents (RTAs), with 60% of head injuries being attributable to RTA and more than 150,000 lives being lost annually due to traumatic brain injury (TBI). These numbers have prompted institutions and organizations at international, national, and local levels to mobilize and address this burden through prevention, prehospital care, and in hospital care. Academic institutions such as Andhra Medical College have run local campaigns promoting the wearing of helmets when riding 2-wheelers. Prehospital care institutions such as Gunupati Venkata Krishna - Emergency Management and Research Institute have also made large strides nationally on delivering safe and timely care through novel and focused education to its emergency medical technicians, applying evidence-based practice to all facets of its work. These changes led to implementation of novel and innovative technological solutions for faster and more efficient responses. National institutions such as the Neurological Society of India (NSI) and Neurotrauma Society of India (NTSI) have been instrumental in promoting safety measures such as use of helmets and seatbelts through social media videos, often using celebrities to disseminate the message. NSI have also focused on sharing best practices for the management of TBI through easy-to-use platforms such as YouTube. Institutions such as American Association of Physicians of Indian Origin, NSI, and NTSI have collaboratively developed TBI management guidelines that are specific to the Indian population (supported by American Association of South Asian Neurosurgeons). Non-governmental organizations such as the Indian Head Injury Foundation and Save Life Foundation have contributed to this movement by promoting awareness through campaigns and public education. While TBI remains a large burden in India, a mobilization and coalesced efforts of such a scale holds promise for tackling this burden., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hydrocephalus is a complex issue characterized by increased intracranial pressure secondary to obstruction of cerebrospinal fluid flow and occasionally due to overproduction. As a result, the entity has challenges of different dimensions at the level of understanding and management., Methods: A literature search, systematic review, and meta-analysis of eligible studies were conducted in the major databases. The literature review included relevant articles on hydrocephalus published until June 1, 2021 (no starting date), databases being the only limitation considering the broadness of the subthemes. Controversies themes were chosen among the literature, not including treatment dilemmas and hydrocephalus research. The further detailed search included these selected themes and an updated literature review on the subjects., Results and Discussion: Controversies are a hallmark of incomplete science; most complex concepts harbor several debates at various levels. This article reviews controversies in hydrocephalus, offering some updates on popular discussions. It is not meant to be an exposition of the topics themselves but to collect the status quo of unresolved concepts in hydrocephalus., Conclusions: As with most chronic and complex disorders, hydrocephalus welcomes controversy as a healthy discussion platform to exist until we understand the disorder to its minutest., Competing Interests: None

Background: Despite current preventative strategies, road traffic collisions (RTCs) and resultant neurotrauma remain a major problem in India. This study seeks to explore local perspectives in the context within which RTCs take place and identify potential suggestions for improving the current status., Methods: Ten semi-structured interviews were carried out with purposively selected key informants from the city of Visakhapatnam, Andhra Pradesh. Participants were from one of the following categories: commissioning stakeholders; service providers; community or local patient group/advocacy group representatives. Transcripts from these interviews were analysed qualitatively using the Framework Method., Results: Participants felt RTCs are a serious problem in India and a leading cause of neurotrauma. Major risk factors identified related to user behaviour such as speeding and not using personal safety equipment, and the user state, namely drink driving and underage driving. Other reported risk factors included poor infrastructure, moving obstacles on the road such as other vehicles, pedestrians and animals, overloaded vehicles and substandard safety equipment. Participants discussed how RTCs affect not only the health of the casualty, but are also a burden to the healthcare system, families, and the national economy. Although there are ongoing preventative strategies being carried out by both the government and the community, challenges to successful prevention emerged from the interviews which included resource deficiencies, inconsistent implementation, lack of appropriate action, poor governance, lack of knowledge and the mindset of the community and entities involved in prevention. Recommendations were given on how prevention of RTCs and neurotrauma might be improved, addressing the areas of education and awareness, research, the pre-hospital and trauma systems, enforcement and legislation, and road engineering, in addition to building collaborations and changing mindsets., Conclusions: RTCs remain a major problem in India and a significant cause of neurotrauma. Addressing the identified gaps and shortfalls in current approaches and reinforcing collective responsibility towards road safety would be the way forward in improving prevention and reducing the burden.

The accumulation of amyloid-β (Aβ) is a characteristic event in the pathogenesis of Alzheimer's disease (AD). Aquaporin 1 (AQP1) is a membrane water channel protein belonging to the AQP family. AQP1 levels are elevated in the cerebral cortex during the early stages of AD, but the role of AQP1 in AD pathogenesis is unclear. We first determined the expression and distribution of AQP1 in brain tissue samples of AD patients and two AD mouse models (3xTg-AD and 5xFAD). AQP1 accumulation was observed in vulnerable neurons in the cerebral cortex of AD patients, and in neurons affected by the Aβ or tau pathology in the 3xTg-AD and 5xFAD mice. AQP1 levels increased in neurons as aging progressed in the AD mouse models. Stress stimuli increased AQP1 in primary cortical neurons. In response to cellular stress, AQP1 appeared to translocate to endocytic compartments of β- and γ-secretase activities. Ectopic expression of AQP1 in human neuroblastoma cells overexpressing amyloid precussir protein (APP) with the Swedish mutations reduced β-secretase (BACE1)-mediated cleavage of APP and reduced Aβ production without altering the nonamyloidogenic pathway. Conversely, knockdown of AQP1 enhanced BACE1 activity and Aβ production. Immunoprecipitation experiments showed that AQP1 decreased the association of BACE1 with APP. Analysis of a human database showed that the amount of Aβ decreases as the expression of AQP1 increases. These results suggest that the upregulation of AQP1 is an adaptive response of neurons to stress that reduces Aβ production by inhibiting the binding between BACE1 and APP., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Strategies to improve traumatic brain injury (TBI) outcomes in India are ill defined. The objective of this study was to examine baseline prehospital (PH) factors associated with outcomes from the Andhra Pradesh Traumatic Brain Injury Project., Methods: We conducted a prospective observational cohort study of adult patients with TBI admitted to the primary referral hospital. Modes of injury, prehospital care and transport, and factors associated with increased in-hospital mortality were evaluated. Poisson regression with robust error variance and adjusted attributable risk percent estimates determined factors associated with outcomes., Results: A total of 447 adults (38% with mild TBI, 30% with moderate TBI, and 32% with severe TBI; 81% men) with isolated TBI (89%) from road traffic accidents (48.1%) or falls (46.5%) were enrolled. Of the patients, 45.7% were transported by ambulance, 61% had scalp/facial bleeding, 11% had respiratory distress, and 7% had cervical spine stabilization. Of these, 25.3% died and 34% had unfavorable outcomes. Among 335 direct admits, 45% traveled more than 50 km and nearly 20% traveled more than 100 km. Bleeding was associated with higher mortality (adjusted relative risk [aRR], 1.56; 95% confidence interval [CI], 1.05-2.31) and unfavorable outcome (aRR, 1.60; 95% CI, 1.18-2.17). Of the patients, 45 (31%) with severe TBI received PH airway management prior to definitive treatment, and respiratory distress was associated with unfavorable discharge outcomes (aRR, 1.23; 95% CI, 1.00-1.51)., Conclusions: Patients with TBI often received treatment far away from injury, bypassing closer hospitals. Scalp/facial bleeding was common and associated with unfavorable outcomes. Ambulance use was infrequent, and few patients received PH airway management, hemorrhage control, or cervical spine stabilization when needed.

OBJECTIVE Neurosurgical services are increasingly recognized as essential components of surgical care worldwide. The degree of interest among neurosurgeons regarding international work, and the barriers to involvement in global neurosurgical outreach, are largely unexplored. The authors distributed a survey to members of the American Association of Neurological Surgeons/Congress of Neurological Surgeons (AANS/CNS) Joint Section on Pediatric Neurosurgery to assess the state of global outreach among its members and to identify barriers to involvement. METHODS An internet-based questionnaire was developed by the International Education Subcommittee of the AANS/CNS Joint Section on Pediatric Neurosurgery and distributed to pediatric neurosurgeons via the AANS/CNS Joint Section email contact list. Participants were surveyed on their involvement in global neurosurgical outreach, geographic location, nature of the participation, and barriers to further involvement. RESULTS A 35.3% response rate was obtained, with 116 respondents completing the survey. Sixty-one percent have performed or taught neurosurgery in a developing country, and 49% travel at least annually. Africa was the most common region (54%), followed by South America (30%), through 29 separate organizing entities. Hydrocephalus was the most commonly treated condition (88%), followed by spinal dysraphism (74%), and tumor (68%). Most respondents obtained follow-up through communications from local surgeons (77%). Seventy-one percent believed the international experience improved their practice, and 74% were very or extremely interested in working elsewhere. Interference with current practice (61%), cost (44%), and difficulty identifying international partners (43%) were the most commonly cited barriers to participation. CONCLUSIONS Any coordinated effort to expand global neurosurgical capacity begins with appreciation for the current state of outreach efforts. Increasing participation in global outreach will require addressing both real and perceived barriers to involvement. Creation and curation of a centralized online database of ongoing projects to facilitate coordination and involvement may be beneficial.

Acetazolamide (AZA), used in treatment of early or infantile hydrocephalus, is effective in some cases, while its effect on the choroid plexus (CP) remains ill-defined. The drug reversibly inhibits aquaporin-4 (AQP4), the most ubiquitous "water pore" in the brain, and perhaps modulation of AQP1 (located apically on CP cells) by AZA may reduce cerebrospinal fluid (CSF) production. We sought to elucidate the effect of AZA on AQP1 and fluid flow in CP cell cultures.CP tissue culture from 10-day Sprague-Dawley rats and a TRCSF-B cell line were grown on Transwell permeable supports and treated with 100 μM AZA. Fluid assays to assess direction and extent of fluid flow, and AQP1 expression patterns by immunoblot, Immuncytochemistry (ICC), and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) were performed.Immunoblots and ICC analyses showed a decrease in AQP1 protein shortly after AZA treatment (lowest at 12 h), with transient AQP1 reduction mediated by mRNA expression (lowest at 6 h). Transwell fluid assays indicated a fluid shift at 2 h, before significant changes in AQP1 mRNA or protein levels.Timing of AZA effect on AQP1 suggests the drug alters protein transcription, while affecting fluid flow by a concomitant method. It is plausible that other mechanisms account for these phenomena, as the processes may occur independently.

Background: Hydrocephalus occurs because of an imbalance of bulk fluid flow in the brain, and aquaporins (AQPs) play pivotal roles in cerebral water movement as essential mediators during edema and fluid accumulation. AQP1 is a water channel found in the choroid plexus (CP), and AQP4 is expressed at the brain-CSF interfaces and astrocytic end feet; excessive fluid accumulation may involve expression of changes in these AQPs during various stages of hydrocephalus., Objective: To determine the alterations of CP AQP1 expression in congenital hydrocephalus; detect hydrocephalus-induced AQP1 expression in the cortical parenchyma, ependyma, and pia mater of hydrocephalic animals; and evaluate AQP4 expression in congenital hydrocephalus through progressive stages of the condition., Methods: We evaluated differential expression of AQPs 1 and 4 in the congenital hydrocephalus Texas rat at postnatal days 5, 10, and 26 in isolated CP and cortex by enzyme-linked immunosorbent assay, Western blot, quantitative reverse transcriptase polymerase chain reaction, and immunohistochemistry., Results: The CP exhibited a 34% decrease in AQP1 expression in young hydrocephalic pups (postnatal days 5 and 10), which became normal (postnatal day 26) just before death. With advancing hydrocephalus, expression of AQPs 1 and 4 increased at the brain-CSF interfaces; AQP1 was localized to the endothelium of cortical capillaries with increased AQP4 expression in surrounding astrocytes end feet. AQP1 expression level was increased in the pia mater, with prominent AQP4 expression in the subpial layers. Subependymal capillaries expressed AQP1 in the endothelium, with increasing AQP4 expression in surrounding astrocytes. Hydrocephalic animals (postnatal day 26) had significant nonendothelial (CD34) AQP1 expression in the septal nucleus of the basal forebrain, an area affected by increased intracranial pressure., Conclusion: Biphasic AQP1 expression in the CP with increased AQPs 1 and 4 at the brain-fluid interfaces may indicate compensatory mechanisms to regulate choroidal cerebrospinal fluid secretion and increase parenchymal fluid absorption in the high-pressure hydrocephalic condition.

The cell fate determinant Numb exists in four alternatively spliced variants that differ in the length of their PTB (phosphotyrosine-binding domain, either lacking or containing an 11 amino acid insertion) and PRR (proline-rich region, either lacking or containing a 48 amino acid insertion). We previously reported that Numb switches from isoforms containing the PTB insertion to isoforms lacking this insertion in neural cultures subjected to stress induced by trophic factor withdrawal. The switch in Numb isoforms enhances the generation of amyloid-β peptide (Aβ), the principle component of senile plaques in Alzheimer's disease (AD). Here we examine the expression of the Numb isoforms in brains from AD patients and triple transgenic (3xTg) AD mice. We found that levels of the Numb isoforms lacking the PTB insertion are significantly elevated in the parietal cortex but not in the cerebellum of AD patients when compared to control subjects. Levels of Numb isoforms lacking the PTB insertion were also elevated in the cortex but not cerebellum of 12 month-old 3xTg AD mice with Aβ deposits compared to younger 3xTg-AD mice and to non-transgenic mice. Exposure of cultured neurons to Aβ resulted in an increase in the levels of Numb isoforms lacking the PTB domain, consistent with a role for Aβ in the aberrant expression of Numb in vulnerable brain regions of AD patients and mice. Collectively, the data show that altered expression of Numb isoforms in vulnerable neurons occurs during AD pathogenesis and suggest a role for Numb in the disease process.

Malignant ectomesenchymoma is a rare tumor arising from mature ganglion cells with immature myogenous elements, with only 4 pediatric intracranial cases having been previously reported. The authors report a rare case of intracranial malignant ectomesenchymoma originating from the falx cerebri in a 10-year-old boy. The patient presented with a 2-week history of headache, nausea, and blurry vision, with mild lateral gaze diplopia. A CT scan revealed a solitary 7.2 × 3.8-cm dural-based mass that extended along the falx. No metastatic disease was identified, and the lesion was grossly resected without complication. Pathological investigation identified single and small groups of cells in a myxoid background, with polygonal or spindle-shaped cells containing eccentric nuclei and prominent nucleoli. Immunohistochemical staining of some cells was positive for smooth-muscle actin, CD99, and vimentin, whereas other cells (often process forming) were positive for S100 protein, synaptophysin, and neurofilament protein. Staining was negative for CD138, CD45, α-fetoprotein, CK AE1/3, glial fibrillary acidic protein, CK7, CK20, CD31, CD34, myoD, and desmin. Normal immunopositivity was seen for INI-1. The Ki 67 immunostaining had < 25% reactivity. The patient was treated with a sarcoma-based chemotherapy regimen and radiation to the craniospinal axis, and was found to be without recurrence or metastatic disease at 20 months.

The Notch signaling pathway plays an essential role in the regulation of cell specification by controlling differentiation, proliferation, and apoptosis. Numb is an intrinsic regulator of the Notch pathway and exists in four alternative splice variants that differ in the length of their phosphotyrosine-binding domain (PTB) and proline-rich region domains. The physiological relevance of the existence of the Numb splice variants and their exact regulation are still poorly understood. We previously reported that Numb switches from isoforms containing the insertion in PTB to isoforms lacking this insertion in neuronal cells subjected to trophic factor withdrawal (TFW). The functional relevance of the TFW-induced switch in Numb isoforms is not known. Here we provide evidence that the TFW-induced switch in Numb isoforms regulates Notch signaling strength and Notch target gene expression. PC12 cells stably overexpressing Numb isoforms lacking the PTB insertion exhibited higher basal Notch activity and Notch-dependent transcription of the transient receptor potential channel 6 (TRPC6) when compared with those overexpressing Numb isoforms with the PTB insertion. The differential regulation of TRPC6 expression is correlated with perturbed calcium signaling and increased neuronal vulnerability to TFW-induced death. Pharmacological inhibition of the Notch pathway or knockdown of TRPC6 function ameliorates the adverse effects caused by the TFW-induced switch in Numb isoforms. Taken together, our results indicate that Notch and Numb interaction may influence the sensitivity of neuronal cells to injurious stimuli by modulating calcium-dependent apoptotic signaling cascades.

Testis-specific gene antigen 10 (TSGA10) encodes an 82-kDa protein expressed during development, and in testis and brain tissues. We report its expression in human monocyte-derived dendritic cells (DC) and macrophages in vitro and in murine spleen CD11c(+) cells ex vivo. An interaction between DC/macrophage-derived TSGA10 and vimentin, as well as a few other major cytoskeletal proteins (e.g., actin-γ1), was identified by pull-down and mass spectroscopy assays. The interaction between TSGA10 and vimentin was further confirmed by immunoprecipitation and immunolocalisation in transfected RAW267 and HEK293 cell lines. TSGA10 formed filamentous structures in transfected COS-1 cells and was observed in cellular projections. We propose that TSGA10 could influence the function of antigen presenting cells (APC) via its interaction with cytoskeletal proteins such as vimentin., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Glioblastoma multiforme (GBM) is the most frequent and incurable type of brain tumor of adults. Hypoxia has been shown to direct GBM toward a more aggressive and malignant state. Here we show that hypoxia increases Notch1 activation, which in turn induces the expression of transient receptor potential 6 (TRPC6) in primary samples and cell lines derived from GBM. TRPC6 is required for the development of the aggressive phenotype because knockdown of TRPC6 expression inhibits glioma growth, invasion, and angiogenesis. Functionally, TRPC6 causes a sustained elevation of intracellular calcium that is coupled to the activation of the calcineurin-nuclear factor of activated T-cell (NFAT) pathway. Pharmacologic inhibition of the calcineurin-NFAT pathway substantially reduces the development of the malignant GBM phenotypes under hypoxia. Clinically, expression of TRPC6 was elevated in GBM specimens in comparison with normal tissues. Collectively, our studies indicate that TRPC6 is a key mediator of tumor growth of GBM in vitro and in vivo and that TRPC6 may be a promising therapeutic target in the treatment of human GBM.

Introduction: We report a case of shunt malfunction after a child was subjected to G forces during a roller coaster ride., Discussion: The temporal sequence of events suggests proximal catheter obstruction with subsequent symptoms of raised intracranial pressure immediately after experience with a G force ride. A shunt revision with catheter change led to resolution of symptoms, and findings were consistent with hemorrhage within the catheter., Conclusion: This case illustrates the risks of such an experience on children with shunts and the implications for patient counseling.

Background: There is mounting evidence that spinal fluid absorption takes place not only at the arachnoid villi, but also at several extracranial sites, which might serve as a reserve mechanism for, or be primarily involved in the absorption of CSF in hydrocephalus., Methods: We compared the nasal lymphatic pathway in congenital Hydrocephalus-Texas (H-Tx) rats in unaffected and affected hydrocephalic (HC) siblings with that of control Sprague Dawley (SD) rat pups. The animals were examined after immediate post mortem injection of Evan's blue dye into the cisterna magna at 6 and 10 days of age. The specimens were evaluated for amount of dye penetration into the nasal passages., Results: We found more dye visualization in the olfactory regions of control SD (14/16 at P6, 14/16 at P10) and unaffected H-Tx (13/17 at P6, 13/16 at P10) compared with HC animals (0/14 at P6, 3/15 at P10). This difference was more pronounced at 10 days of age. The dye was not visualized in the cervical lymph nodes or venous channels in these acute experiments., Conclusion: The results of this study suggest that nasal lymphatic cerebrospinal fluid absorption is reduced in the H-Tx rat hydrocephalus model.

In March 2004, a multidisciplinary conference, "ITB Therapy Best Practice Forum," was held in Minneapolis, Minnesota. The goal of the conference was to develop recommendations for techniques to implant intrathecal baclofen (ITB) pump and catheter systems more effectively and with fewer complications. The authors present the techniques for optimal pump and catheter implantation, including subfascial pump placement; insertion of the Tuohy needle in an oblique, paramedian trajectory; and positioning of the catheter tip at levels commensurate with the therapeutic indication: approximately T10-12 for spastic diplegia, C5-T2 for spastic tetraparesis, and C1-4 for generalized secondary dystonia. Techniques to minimize the incidence of cerebrospinal fluid leakage are described, including the identification of preoperative occult hydrocephalus and the use of a suture ligature around the Tuohy needle at its exit site from the fascia. Techniques to minimize surgery-related infection are also detailed; most involve the use of iodine solutions multiple times intraoperatively. Techniques to insert intrathecal catheters during spinal fusion are addressed, particularly the technique of inserting the catheter cephalad to the fusion site. Panel members advocate the aforementioned techniques to improve the efficacy of and decrease the morbidity associated with ITB therapy.