Proliferative Index in Pediatric Pilocytic Astrocytoma by Region of Origin and Prediction of Clinical Behavior.

BACKGROUND/AIMS: Pilocytic astrocytomas are common pediatric tumors. Molecular profiles vary with location of origin. Comparisons of proliferation have not been reported. We sought to identify differences in growth by region and whether these predict clinical behavior. METHODS: A retrospective review of all patients undergoing surgery for a pilocytic astrocytoma at Children's Hospital LA from 2003 to 2015 was completed. Tumor location, determined by imaging, was stratified into infratentorial, supratentorial, or optic pathway. Proliferation was measured by Ki-67 immunostaining. A p value of 0.05 was deemed significant. RESULTS: 77 patients were identified. 51 had posterior fossa tumors, 12 had supratentorial tumors, and 14 had optic pathway tumors. Mean Ki-67 score was 3.67, 4.09, and 3.83%, respectively (p = 0.82). Ki-67 of ≥4% trended towards recurrence (p = 0.11), incomplete resection (p = 0.15), and younger age at presentation (p = 0.04). Ki-67 was weakly correlated with shorter survival after surgery (r = -0.103, p = 0.41). Partial resection strongest predicted recurrence (p < 0.001; OR = 13.0). CONCLUSION: Proliferative index does not change by location. Higher cell proliferation was seen in younger patients and associated with shorter time to and a higher risk of recurrence. Further study is needed to identify predictors for clinical behavior. Importance of Study: This study provides a detailed analysis of the proliferative indices of tumors arising from characteristic locations within the brain. With recent advances in our understanding of the differences in molecular and genetic profiles despite similar histologic diagnoses, we felt that it was important to review whether there were unique components of tumor behavior that could be identified. In turn, we sought to determine whether tumor behavior could be used to predict the clinical course. This knowledge is important, given that not every tumor may undergo complete surgical resection, and that some lesions may require more aggressive upfront adjuvant therapy or be closely monitored for recurrence.

Neuronal Rac1 is required for learning-evoked neurogenesis.

Hippocampus-dependent learning and memory relies on synaptic plasticity as well as network adaptations provided by the addition of adult-born neurons. We have previously shown that activity-induced intracellular signaling through the Rho family small GTPase Rac1 is necessary in forebrain projection neurons for normal synaptic plasticity in vivo, and here we show that selective loss of neuronal Rac1 also impairs the learning-evoked increase in neurogenesis in the adult mouse hippocampus. Earlier work has indicated that experience elevates the abundance of adult-born neurons in the hippocampus primarily by enhancing the survival of neurons produced just before the learning event. Loss of Rac1 in mature projection neurons did reduce learning-evoked neurogenesis but, contrary to our expectations, these effects were not mediated by altering the survival of young neurons in the hippocampus. Instead, loss of neuronal Rac1 activation selectively impaired a learning-evoked increase in the proliferation and accumulation of neural precursors generated during the learning event itself. This indicates that experience-induced alterations in neurogenesis can be mechanistically resolved into two effects: (1) the well documented but Rac1-independent signaling cascade that enhances the survival of young postmitotic neurons; and (2) a previously unrecognized Rac1-dependent signaling cascade that stimulates the proliferative production and retention of new neurons generated during learning itself.

The α crystallin domain of small heat shock protein b8 (Hspb8) acts as survival and differentiation factor in adult hippocampal neurogenesis.

Adult hippocampal neurogenesis is to a large degree controlled at the level of cell survival, and a number of potential mediators of this effect have been postulated. Here, we investigated the small heat shock protein Hspb8, which, because of its pleiotropic prosurvival effects in other systems, was considered a particularly promising candidate factor. Hspb8 is, for example, found in plaques of Alzheimer disease but exerts neuroprotective effects. We found that expression of Hspb8 increased during differentiation in vitro and was particularly associated with later stages (48-96 h) of differentiation. Gain-of-function and loss-of-function experiments supported the hypothesis that Hspb8 regulates cell survival of new neurons in vitro. In the dentate gyrus of adult mice in vivo, lentiviral overexpression of Hspb8 doubled the surviving cells and concomitantly promoted differentiation and net neurogenesis without affecting precursor cell proliferation. We also discovered that the truncated form of the crystallin domain of Hspb8 was sufficient to affect cell survival and neuronal differentiation in vitro and in vivo. Precursor cell experiments in vitro revealed that Hspb8 increases the phosphorylation of Akt and suggested that the prosurvival effect can be produced by a cell-autonomous mechanism. Analysis of hippocampal Hspb8 expression in mice of 69 strains of the recombinant inbred set BXD revealed that Hspb8 is a cis-acting gene whose expression was associated with clusters of transcript enriched in genes linked to growth factor signaling and apoptosis. Our results strongly suggest that Hspb8 and its α-crystallin domain might act as pleiotropic prosurvival factor in the adult hippocampus.

Natural killer cell-activating receptor NKG2D mediates innate immune targeting of allogeneic neural progenitor cell grafts.

Cell replacement therapy holds promise for a number of untreatable neurological or psychiatric diseases but the immunogenicity of cellular grafts remains controversial. Emerging stem cell and reprogramming technologies can be used to generate autologous grafts that minimize immunological concerns but autologous grafts may carry an underlying genetic vulnerability that reduces graft efficacy or survival. Healthy allogeneic grafts are an attractive and commercially scalable alternative if immunological variables can be controlled. Stem cells and immature neural progenitor cells (NPC) do not express major histocompatibility complex (MHC) antigens and can evade adaptive immune surveillance. Nevertheless, in an experimental murine model, allogeneic NPCs do not survive and differentiate as well as syngeneic grafts, even when traditional immunosuppressive treatments are used. In this study, we show that natural killer (NK) cells recognize the lack of self-MHC antigens on NPCs and pose a barrier to NPC transplantation. NK cells readily target both syngeneic and allogeneic NPC, and killing is modulated primarily by NK-inhibiting "self" class I MHC and NK-activating NKG2D-ligand expression. The absence of NKG2D signaling in NK cells significantly improves NPC-derived neuron survival and differentiation. These data illustrate the importance of innate immune mechanisms in graft outcome and the potential value of identifying and targeting NK cell-activating ligands that may be expressed by stem cell derived grafts.

Lack of efficacy of motor cortex stimulation for the treatment of neuropathic pain in 14 patients.

OBJECTIVES: Motor cortex stimulation has been reported as an effective treatment for medically resistant neuropathic pain. The goal of this study is to review the efficacy of this treatment in a series of 14 patients. MATERIALS AND METHODS: The records of a consecutive series of 14 patients undergoing MCS for neuropathic pain at Stanford University Hospital and Clinics between 2002 and 2010 were retrospectively analyzed. The primary outcome measure was a visual analogue scale, which patients completed prior to surgery and following each programming session. The motor cortex was localized using 1) MR image guidance, 2) intraoperative somatosensory evoked potentials and motor response to stimulation, and 3) postoperative imaging. All patients underwent extensive stimulator programming. RESULTS: Five patients exhibited a transient improvement of >50%. Of these, only two patients maintained >50% improvement to their last clinic visit. One of these patients died of unrelated causes, and the other complained of variable response at home. The median time from best to final VAS was 50 days. Average postoperative follow-up was 55.5 weeks. Postoperative imaging demonstrated appropriate lead placement in 12 patients. The other two patients did not undergo postoperative imaging. CONCLUSIONS: In our cohort of 14 patients with neuropathic pain, motor cortex stimulation failed to produce acceptable long-term benefit. Possible reasons for this failure are discussed in the context of a small retrospective study.

Hepatocellular carcinoma metastatic to the pituitary gland without an identifiable primary lesion.

Hepatocellular carcinoma is one of the most common malignancies worldwide. However, brain metastases from this cancer are incredibly rare. While the hepatocellular carcinoma mortality rate in the United States has been increasing, hepatocellular carcinoma is rare among patients without underlying liver disease. Here we present a patient with a history of left optic nerve meningioma treated with stereotactic radiosurgery who presented with acute vision loss. Magnetic resonance imaging revealed an enhancing mass lesion in the region of the sella turcica. Neurosurgical histopathology revealed a metastatic lesion consistent with hepatocellular carcinoma. Systemic workup failed to identify a primary liver lesion.

Intracranial malignant peripheral nerve sheath tumor: A case report and comprehensive literature review.

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are rare malignant soft-tissue sarcomas arising from peripheral nerves. Little data exist regarding MPNST originating intracranially. Here, we present a 7th/8th nerve complex MPNST, discuss the treatment strategy and patient outcome, and provide a comprehensive review of existing literature. Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, PubMed and crossed references were queried, yielding 37 publications from 1952 to the present. Fifty-three cases of primary intracranial and extra-axial MPNST were identified. Results: We additionally report a 40-year-old female presented with acute onset dizziness and subsequent hearing loss with associated right-sided facial numbness. Magnetic resonance imaging revealed a 0.5 cm × 1.7 cm enhancing lesion within the right internal auditory canal extending into the cerebellopontine angle. The patient was initially treated with retro sigmoid craniotomy for tumor resection followed by a trans labyrinth approach for residual tumor resection. She completed adjuvant fractionated radiation therapy and underwent facial nerve transfer to restore complete hemifacial paralysis. The most common cranial nerves involved were V and VIII (43.4% each), with 66% of patients male and 34% female. The average age was 43.4 ± 17.4 years. The mean survival time for reported non-survivors after tissue diagnosis was 15 ± 4 months. Two-year survival for patients receiving gross total resection was 33.3% versus 22.8% with subtotal resection. Conclusion: MPNSTs comprise a group of highly aggressive neoplasms that rarely arise intracranially. Gross total surgical resection should be pursued when feasible.

Metastatic choroid plexus papilloma presenting as a sellar mass: A case report and literature review.

Background: Choroid plexus papillomas (CPPs) are rare neoplasms arising from choroid plexus epithelium representing <1% of all intracranial tumors. Symptoms vary based on location and regional mass effect; however, hydrocephalus is common due to cerebrospinal fluid flow obstruction and/or overproduction. Distant site metastasis or de novo formation in extraventricular sites is rare. Case Description: A 57-year-old female with a history of a 4th ventricular CPP status post resection in 2004 and 2018 with subsequent gamma knife therapy in 2019 presented with increased thirst and urination. Since her initial surgery, she has experienced significant gait imbalance, diplopia, dysphagia, and right-sided hemiparesis and hemisensory loss. Magnetic resonance imaging revealed a new 1.5 × 1.8 cm suprasellar lesion. She underwent a left supraorbital craniotomy for tumor resection, with pathology revealing metastatic World Health Organization grade II CPP. Conclusion: Extraventricular manifestation of CPP is rare. De novo or metastatic involvement of the sella has seldom been reported. Treatment should target gross total surgical resection. Adjuvant chemotherapy and radiation may be useful in higher-grade lesions.

Pylabianca: comprehensive and user­friendly Python package for single­neuron data analysis.

In the area of electrophysiology, the availability of comprehensive and user­friendly tools for single-neuron data processing, statistical analysis, and fast, intuitive data visualization is limited. To address this gap, we introduce pylabianca, a Python library tailored for robust single and multi­unit data processing. Pylabianca leverages the power of standard Python packages and adopts the application programming interface of MNE­Python, one of the most widely used electrophysiology packages. One of pylabianca's primary objectives is to provide a low entry threshold for scientists, requiring only basic Python programming skills. Pylabianca was designed to streamline most common analyses of single neuron data, and provide convenient data structures to serve as a foundation for building custom analysis pipelines. We believe that pylabianca will contribute to enhancing researchers' capabilities and efficiency in the field of single-neuron electrophysiology.

Association of Early Childhood Caries with Body Mass Index, Dietary Habits, and Socioeconomic Status among Preschool Children of Kelambakkam.

Introduction: One of the most prevalent oral diseases affecting preschoolers, early childhood caries (ECC), can significantly lower a child's quality of life. The pain and discomfort that ECC causes will alter the child's eating habits, which will have an impact on both their physical and mental health, as shown by the deviation from the body mass index (BMI). Dental caries and deviation from the normal BMI are both significantly influenced by children's eating habits and socioeconomic status (SES). Aim: To determine the association of ECC with BMI, dietary habits, and SES among 3-6-year-old preschool children. Materials and methods: A cross-sectional study was conducted among 375 preschool children of 3-6 years of age. The decayed, missing, or filled teeth (deft) index was used to determine the caries status. Measurement of height (m) and weight (kg) was done using a stadiometer and electronic weighing machine. For each child, the BMI (kg/m2) was calculated, and the child's body weight status was assessed using Centers for Disease Control and Prevention (CDC)-based classification. Questionnaires were collected with demographic details, 3 days diet diary, and the SES of parents. The dietary habit and SES were obtained from the healthy eating index-2005 (HEI-2005) score and Modified Kuppuswamy's Scale 2018. All the data were entered and analyzed using Statistical Package for the Social Sciences (SPSS) software V 20.0. Result: The prevalence of ECC was 44.8%. On comparison of mean height, weight, and BMI scores, there was a significant difference in mean weight (p = 0.006) and BMI (p = 0.001) among the two study groups. Children with ECC had a lower HEI-2005 score and belonged to a lower social class compared to caries-free children (p = 0.001). Conclusion: Children with ECC are significantly associated with BMI being overweight, or risk of being overweight; lower grades of SES and lower total score of HEI-2005 with poor diet and diet that needs improvement. How to cite this article: Suresh A, Srinivasan D, AR SE, et al. Association of Early Childhood Caries with Body Mass Index, Dietary Habits, and Socioeconomic Status among Preschool Children of Kelambakkam. Int J Clin Pediatr Dent 2023;16(4):565-571.

Dural lymphoma misdiagnosed as subdural hematoma following head trauma after an episode of syncope.

Primary dural lymphoma is a rare subtype of primary central nervous system lymphoma. Primary dural lymphoma may be radiologically misdiagnosed as it shares similar imaging characteristics with several pathologies, including meningiomas and subdural or epidural hematomas. We present a patient who was originally diagnosed with a subdural hematoma following a syncopal episode on computed tomography. Follow-up magnetic resonance imaging of the brain demonstrated heterogeneously enhancing dural-based mass overlying the left frontoparietal convexity associated with bidirectional dural tails, suggestive of a malignant meningioma. Neurosurgical histopathology revealed marginal zone B-cell lymphoma. This case represents the potential difficulty in diagnosing primary dural lymphoma, especially in the setting of uncertain clinical history and obscured imaging features.

Transplantation of human neural progenitor cells secreting GDNF into the spinal cord of patients with ALS: a phase 1/2a trial.

Amyotrophic lateral sclerosis (ALS) involves progressive motor neuron loss, leading to paralysis and death typically within 3-5 years of diagnosis. Dysfunctional astrocytes may contribute to disease and glial cell line-derived neurotrophic factor (GDNF) can be protective. Here we show that human neural progenitor cells transduced with GDNF (CNS10-NPC-GDNF) differentiated to astrocytes protected spinal motor neurons and were safe in animal models. CNS10-NPC-GDNF were transplanted unilaterally into the lumbar spinal cord of 18 ALS participants in a phase 1/2a study (NCT02943850). The primary endpoint of safety at 1 year was met, with no negative effect of the transplant on motor function in the treated leg compared with the untreated leg. Tissue analysis of 13 participants who died of disease progression showed graft survival and GDNF production. Benign neuromas near delivery sites were common incidental findings at post-mortem. This study shows that one administration of engineered neural progenitors can provide new support cells and GDNF delivery to the ALS patient spinal cord for up to 42 months post-transplantation.

Ayurvedic visha hara (antitoxic) chikitsa in recurrent dyshidrotic eczema skin disease: A case report.

Dyshidrotic eczema is a chronic, enigmatic condition that usually affects the hands and feet that probably accounts for about 5%-20% of hand eczemas. In Ayurveda various skin manifestation are mentioned under different chapter & context like kushtha, visarpa, kshudra kushtha, vidradi, krimi roga, keeta visha (insect bite), Garavisha &Dooshi visha (latent toxicity).Visphota variety of kushtha is characterized by pustules which are either white or reddish in appearance. These pustules have a thin skin and it is pitta-kapha predominant. The ayurvedic diagnosis was made as "Dushivisha janya visaphota kushtha" and treatment was done basis on this. There was not a single cases on the internet treated on Ayurvedic line of management thus the present article was prepared to assess the role of Visha Hara and Rasayan Chikitsa in such emerging automimmune skin condition. Improvement in the skin lesion were observed after a period of 1 months of regular treatment and complete remission with no further attack after 2-month follow-up. The improvement was observable through the follow-up photograph.

Pituitary microadenoma with hypopituitarism presenting as hyponatremia.

The incidence of pituitary adenoma has been increasing these days. Majority of the cases are incidental findings on imaging; and these patients may be asymptomatic without any laboratory abnormalities. However, a non-functional sellar mass can initially present with hypopituitarism. The patient being described is an elderly female who presented with severe hyponatraemia. She has history of recurrent admissions for hyponatraemia in the past. Her biochemical evaluation revealed hypopituitarism and magnetic resonance imaging of brain showed pituitary microadenoma. Hyponatraemia as a presenting feature of hypopituitarism due to pituitary microadenoma is an uncommon scenario.

Multifocal spinal glioblastoma and leptomeningeal carcinomatosis in an elderly male with hydrocephalus and myelopathy.

BACKGROUND: Primary spinal glioblastoma multiforme with multifocal leptomeningeal enhancement is rarely diagnosed or documented. We describe a rare case of multifocal spinal isocitrate dehydrogenase (IDH) wild type glioblastoma with leptomeningeal carcinomatosis in an elderly male presenting with a chronic subdural hematoma, progressive myelopathy, and communicating hydrocephalus. CASE DESCRIPTION: A 77-year-old male with a medical history of an acoustic schwannoma, anterior cranial fossa meningioma, and immune thrombocytopenic purpura presented with right-sided weakness after repeated falls. Magnetic resonance imaging of the brain and spine demonstrated a left-sided subdural hematoma, leptomeningeal enhancement of the brain and skull base, ventricles, and the cranial nerves, and along with florid enhancement of the leptomeninges from the cervicomedullary junction to the cauda equina. Most pertinent was focal thickening of the leptomeninges at T1 and T6 with mass effect on the spinal cord. A T6 laminectomy with excisional biopsy of the lesion was planned and completed. Findings were significant for glioblastoma the World Health Organization Grade IV IDH 1 wild type of the thoracic spinal cord. Subsequently, his mental status declined, and he developed progressive hydrocephalus which required cerebrospinal fluid diversion. Unfortunately, the patient had minimal improvement in his neurological exam and unfortunately died 2 months later. CONCLUSION: In a review of the limited literature describing similar cases of primary spinal glioblastoma, the prognosis of this aggressive tumor remains unfavorable, despite aggressive treatment options. The purpose of this report is to increase awareness of this rare condition as a potential differential diagnosis in patients presenting with multifocal invasive spinal lesions.

Biomedical waste management practice in dentistry.

Biomedical Waste Management practice in Dentistry is an important issue. Therefore, it is of interest to document awareness on such issues among clinical practitioners, academicians and students. A survey was completed using a questionnaire from 355 dentists consisting of 201 students, 39 academicians and 115 clinicians in India. Analysis of the survey data shows that majority of students, practitioners, and academicians are aware of laws binding with such issues. However, the Biomedical Waste Management practice among them is not satisfactory. Therefore, education on such issues among clinical practitioners, academicians and students is critical in this part of the globe.

Feasibility and Pilot Efficacy Testing of Integrated Yoga and Shirodhara (Ayurvedic Oil-Dripping) Intervention on Clinical Symptoms, Cognitive Functions and Sleep Quality of Adults with Anxiety Disorder.

BACKGROUND: Beneficial effects of yoga therapy in anxiety disorders (ADs) are known. Traditional texts describe usefulness of Ayurvedic oil-dripping, Shirodhara technique, in relieving anxiety. Thus, present study was planned to assess the feasibility and synergistic value of Shirodhara as an add-on to yoga therapy in adults with AD. MATERIALS AND METHODS: Thirty adults (males = 14, females = 16) admitted in a residential holistic health care center with an age range of 29.66 ± 6.63 years and diagnosis of one of the ADs (generalized AD, n = 18; social phobia, n = 8; and panic AD, n = 4) as per mini-international neuropsychiatric interview (M. I. N. I. English version 5.0) by a psychiatrist were randomly divided into two groups: (1) integrated yoga-based lifestyle program (YT; n = 15) and (2) YT + Ayurveda (YA; n = 15). Both groups continued to receive conventional treatment and were on stable medications throughout the study period except in cases of emergency. Assessments were done by an independent assessor at baseline and after 2 weeks of intervention for clinical symptoms (HAM-A, State and Trait Anxiety Inventory, and Brief Psychiatric Rating Scale), sleep quality (sleep rating questionnaire), and cognition (Stroop test and digit letter substitution test) using standard validated tools. Parametric tests were applied using SPSS 10.0 to analyze the data. RESULTS: Twelve subjects in yoga group and thirteen subjects in YA group completed the trial. No side effects were reported in any of the groups. Within-group comparisons showed a significant improvement in clinical symptoms, cognition and sleep quality in both the groups. Between-group comparisons showed significantly better scores in Stroop word task for YA group as compared to YT group. Furthermore, there was a trend toward better improvement in sleep quality for YA group. CONCLUSION: Adding of Shirodhara technique to YT was feasible and may be useful in improving executive memory and sleep quality in adults with ADs.

Lesion Network Mapping Analysis Identifies Potential Cause of Postoperative Depression in a Case of Cingulate Low-Grade Glioma.

BACKGROUND: Depression following resection of diffuse low-grade glioma has rarely been described. Location of the tumor and surgical route are potential causes. Lesion network mapping (LNM), leveraging high-quality resting-state functional magnetic resonance imaging data from large samples of healthy adults, has been used to explore the broader network connectivity for given lesions. However, LNM has not been applied to large intra-axial masses or surgical lesions. We used LNM to examine a potential cause of postoperative depression in a patient with a cingulate diffuse low-grade glioma (zones I-III). CASE DESCRIPTION: A 34-year-old woman underwent surgery for medically refractory seizures attributable to diffuse low-grade glioma. Near-total resection was attained via a single-stage, transcortical route through the medial prefrontal cortex. Despite freedom from seizure and lack of tumor growth at 42 months of follow-up, she developed symptoms of major depressive disorder soon after surgery that persisted. To identify functional networks potentially engaged by the surgical corridor and tumor resection cavity, both were segmented separately and used as seeds for normative resting-state functional magnetic resonance imaging connectivity mapping. To study depression specifically, networks associated with the tumor and surgical approach were compared with networks associated with subgenual cingulate deep brain stimulation. LNM results suggested that the surgical corridor, rather than the tumor, had greater overlap with deep brain stimulation-based depression networks (32% vs. 8%). CONCLUSIONS: Early postoperative development of major depressive disorder following resection of a cingulate region tumor, although likely multifactorial, should be considered and patients appropriately counseled preoperatively. Further validation of LNM as a viable methodology for correlating symptoms to lesions could make it a valuable tool in selection of surgical approach and patient counseling.

Intraoperative navigation-guided resection of anomalous transverse processes in patients with Bertolotti's syndrome.

BACKGROUND: Bertolotti's syndrome is characterized by enlargement of the transverse process at the most caudal lumbar vertebra with a pseudoarticulation between the transverse process and sacral ala. Here, we describe the use of intraoperative three-dimensional image-guided navigation in the resection of anomalous transverse processes in two patients with Bertolotti's syndrome. CASE DESCRIPTIONS: Two patients diagnosed with Bertolotti's syndrome who had undergone the above-mentioned procedure were identified. The patients were 17- and 38-years-old, and presented with severe, chronic low back pain that was resistant to conservative treatment. Imaging revealed lumbosacral transitional vertebrae at the level of L5-S1, which was consistent with Bertolotti's syndrome. Injections of the pseudoarticulations resulted in only temporary symptomatic relief. Thus, the patients subsequently underwent O-arm neuronavigational resection of the bony defects. Both patients experienced immediate pain resolution (documented on the postoperative notes) and remained asymptomatic 1 year later. CONCLUSION: Intraoperative three-dimensional imaging and navigation guidance facilitated the resection of anomalous transverse processes in two patients with Bertolotti's syndrome. Excellent outcomes were achieved in both patients.