Everything old is new again. revisiting hypophysectomy for the treatment of refractory cancer-related pain: a systematic review.

Cancer-related pain is a common and debilitating condition that can significantly affect the quality of life of patients. Opioids, NSAIDs, and antidepressants are among the first-line therapies, but their efficacy is limited or their use can be restricted due to serious side effects. Neuromodulation and lesioning techniques have also proven to be a valuable instrument for managing refractory pain. For patients who have exhausted all standard treatment options, hypophysectomy may be an effective alternative treatment. We conducted a comprehensive systematic review of the available literature on PubMed and Scielo databases on using hypophysectomy to treat refractory cancer-related pain. Data extraction from included studies included study design, treatment model, number of treated patients, sex, age, Karnofsky Performance Status (KPS) score, primary cancer site, lead time from diagnosis to treatment, alcohol injection volume, treatment data, and clinical outcomes. Statistical analysis was reported using counts (N, %) and means (range). The study included data from 735 patients from 24 papers treated with hypophysectomy for refractory cancer-related pain. 329 cancer-related pain patients were treated with NALP, 216 with TSS, 66 with RF, 55 with Y90 brachytherapy, 51 with Gamma Knife radiosurgery (GK), and 18 with cryoablation. The median age was 58.5 years. The average follow-up time was 8.97 months. Good pain relief was observed in 557 out of 735 patients, with complete pain relief in 108 out of 268 patients. Pain improvement onset was observed 24 h after TSS, a few days after NALP or cryoablation, and a few days to 4 weeks after GK. Complications varied among treatment modalities, with diabetes insipidus (DI) being the most common complication. Although mostly forgotten in modern neurosurgical practice, hypophysectomy is an attractive option for treating refractory cancer-related pain after failure of traditional therapies. Radiosurgery is a promising treatment modality due to its high success rate and reduced risk of complications.

Profiling of Tumor-Infiltrating Immune Cells and Their Impact on Survival in Glioblastoma Patients Undergoing Immunotherapy with Dendritic Cells.

Glioblastomas (GBM) are the most common primary malignant brain tumors, comprising 2% of all cancers in adults. Their location and cellular and molecular heterogeneity, along with their highly infiltrative nature, make their treatment challenging. Recently, our research group reported promising results from a prospective phase II clinical trial involving allogeneic vaccination with dendritic cells (DCs). To date, six out of the thirty-seven reported cases remain alive without tumor recurrence. In this study, we focused on the characterization of infiltrating immune cells observed at the time of surgical resection. An analytical model employing a neural network-based predictive algorithm was used to ascertain the potential prognostic implications of immunological variables on patients' overall survival. Counterintuitively, immune phenotyping of tumor-associated macrophages (TAMs) has revealed the extracellular marker PD-L1 to be a positive predictor of overall survival. In contrast, the elevated expression of CD86 within this cellular subset emerged as a negative prognostic indicator. Fundamentally, the neural network algorithm outlined here allows a prediction of the responsiveness of patients undergoing dendritic cell vaccination in terms of overall survival based on clinical parameters and the profile of infiltrated TAMs observed at the time of tumor excision.

The Brainstem Cavernoma Case Series: A Formula for Surgery and Surgical Technique.

Background and Objectives: Cavernous malformations (CM) are vascular malformations with low blood flow. The removal of brainstem CMs (BS) is associated with high surgical morbidity, and there is no general consensus on when to treat deep-seated BS CMs. The aim of this study is to compare the surgical outcomes of a series of deep-seated BS CMs with the surgical outcomes of a series of superficially located BS CMs operated on at the Department of Neurosurgery, College of Tuebingen, Germany. Materials and Methods: A retrospective evaluation was performed using patient charts, surgical video recordings, and outpatient examinations. Factors were identified in which surgical intervention was performed in cases of BS CMs. Preoperative radiological examinations included MRI and diffusion tensor imaging (DTI). For deep-seated BS CMs, a voxel-based 3D neuronavigation system and electrophysiological mapping of the brainstem surface were used. Results: A total of 34 consecutive patients with primary superficial (n = 20/58.8%) and deep-seated (n = 14/41.2%) brainstem cavernomas (BS CM) were enrolled in this comparative study. Complete removal was achieved in 31 patients (91.2%). Deep-seated BS CMs: The mean diameter was 14.7 mm (range: 8.3 to 27.7 mm). All but one of these lesions were completely removed. The median follow-up time was 5.8 years. Two patients (5.9%) developed new neurologic deficits after surgery. Superficial BS CMs: The median diameter was 14.9 mm (range: 7.2 to 27.3 mm). All but two of the superficial BS CMs could be completely removed. New permanent neurologic deficits were observed in two patients (5.9%) after surgery. The median follow-up time in this group was 3.6 years. Conclusions: The treatment of BS CMs remains complex. However, the results of this study demonstrate that with less invasive posterior fossa approaches, brainstem mapping, and neuronavigation combined with the use of a blunt "spinal cord" dissection technique, deep-seated BS CMs can be completely removed in selected cases, with good functional outcomes comparable to those of superficial BS CM.

Safety and Outcomes of Dentate Nucleus Deep Brain Stimulation for Cerebellar Ataxia.

Cerebellar symptoms remain orphan of treatment options despite being prevalent and incapacitating. Investigate whether dentate nucleus deep brain stimulation (DN DBS) is safe and leads to improvements in cerebellar symptoms when compared to sham stimulation. This randomized double-blind crossover pilot trial enrolled five patients with spinocerebellar ataxia type 3 or post-lesion ataxia. Active or sham phases were randomly performed three months apart. The primary outcome was ataxia improvement as measured by the Scale for the Assessment and Rating of Ataxia (SARA) after the active compared to the sham period. Secondary outcome measures included safety and tolerability, the Fahn-Tolosa-Marin Tremor Rating Scale (FTMRS), quality of life measurements, and patients' global impression of change. The effects on ataxia were numerically better in four out of five patients after active versus sham stimulation. The composite SARA score did not change after comparing active to sham stimulation (8.6 ± 3.6 versus 10.1 ± 4.1; p = 0.223). The FTMRS showed significant improvement after active stimulation versus sham (18.0 ± 17.2 versus 22.2 ± 19.5; p = 0.039) as did patients' global impression of change (p = 0.038). The quality of life was not modified by stimulation (p = 0.337). DN DBS was well tolerated without serious adverse events. One patient had the electrode repositioned. DN DBS is a safe and well tolerated procedure that is effective in alleviating cerebellar tremor. In this small cohort of ataxic patients, DN DBS did not achieve statistical significance for ataxia improvement.

Near-Complete Remission of Glioblastoma in a Patient Treated with an Allogenic Dendritic Cell-Based Vaccine: The Role of Tumor-Specific CD4+T-Cell Cytokine Secretion Pattern in Predicting Response and Recurrence.

Immunotherapy has brought hope to the fight against glioblastoma, but its efficacy remains unclear. We present the case of CST, a 25-year-old female patient with a large right-hemisphere glioblastoma treated with a dendritic-tumor cell fusion vaccine. CST showed a near-complete tumor response, with a marked improvement in her functional status and simultaneous increases in tumor-specific CD8+ and CD4+ T cells. Two months before recurrence, the frequency of tumor-specific T cells decreased, while that of IL-17 and CD4+ T cells increased. CST passed away 15 months after enrollment. In this illustrative case, the tumor-specific CD4+ T-cell numbers and phenotype behaved as treatment efficacy biomarkers, highlighting the key role of the latter in glioblastoma immunotherapy.

Laser-evoked potentials recover gradually when using dorsal root ganglion stimulation, and this influences nociceptive pathways in neuropathic pain patients.

OBJECTIVE: Dorsal root ganglion stimulation (DRGS) is able to relieve chronic neuropathic pain. There seems evidence that DRGS might achieve this by gradually influencing pain pathways. We used laser-evoked potentials (LEP) to verify our hypothesis that the recovery of the LEP may reflect DRGS-induced changes within the nociceptive system. METHODS: Nine patients (mean age 56.8 years, range 36-77 years, two females) diagnosed with chronic neuropathic pain in the knee or groin were enrolled in the study. We measured each patient's LEP at the painful limb and contralateral control limb on the first, fourth, and seventh day after implantation of the DRGS system. We used the numeric rating scale (NRS) for the simultaneous pain assessment. RESULTS: The LEP amplitude of the N2-P2 complex showed a significant increase on day 7 when compared to day 1 (Z = -2.666, p = 0.008) and to day 4 (Z = -2.547, p = 0.011), respectively. There was no significant difference in the N2-P2 complex amplitude between ON and OFF states during DRGS. The patients' NRS significantly decreased after 1 day (p = 0.007), 4 days (p = 0.007), and 7 days (p = 0.007) when compared to the baseline. CONCLUSIONS: The results show that with DRGS, the LEP recovered gradually within 7 days in neuropathic pain patients. Therefore, reduction of the NRS in patients with chronic neuropathic pain might be due to DRGS-induced processes within the nociceptive system. These processes might indicate neuroplasticity mediated recovery of the LEP.

Electrophysiological predictors of hearing deterioration based on AEP monitoring during petroclival meningioma resection.

The objective of this study was to calculate the risk of postsurgical hearing deterioration as a function of changes in the amplitude and latency of the most stable components (waves III and V) of the auditory evoked potential (AEP) during petroclival meningioma resection surgery. We retrospectively analyzed intraoperative AEP monitoring results and pre- and postsurgical hearing status in 40 consecutive patients who were surgically treated for petroclival meningiomas. Statistical analyses were conducted to identify the most sensitive and specific way to predict hearing dysfunction after surgery. Patients' mean age was 59 ± 10 years, and 31 (77.5%) were women. Twelve (30%) patients presented with clinically detectable hearing impairment preoperatively. At the first postoperative assessment, four of those 12 patients reported subjective improvement, and eight reported hearing deterioration. Of those eight, four remained stable and four recovered hearing by the last assessment. Wave III latency reached its highest specificity (100%) and sensitivity (71.43%) at x = 143%. Wave V latency, on the other hand, reached its highest sensitivity (71%) and specificity (93%) at x = 124%. Finally, wave V amplitude reached its highest sensitivity (100%) and specificity (79%) at x = 74%. Intraoperative alterations of wave III latency and wave V amplitude seem to be highly sensitive and specific at predicting the risk of auditory dysfunction in patients undergoing petroclival meningioma resection and should be used to determine maximum resection with preservation of function.

Characterization of traumatic spinal cord injury model in relation to neuropathic pain in the rat.

Purpose/aim: Neuropathic pain following spinal cord injury (SCI) has a tremendous impact on patient's quality of life, and frequently is the most limiting aspect of the disease. In view of the severity of this condition and the absence of effective treatments, the establishment of a reliable animal model that reproduces neuropathic pain after injury is crucial for a better understanding of the pathophysiology and for the development of new therapeutic strategies. Thus, the objective of the present study was to standardize the traumatic SCI model in relation to neuropathic pain. MATERIALS AND METHODS: Wistar rats were submitted to SCI of mild intensity (pendulum height 12.5 mm) or moderate intensity (pendulum height 25 mm) using the New York University Impactor equipment. Behavioural assessment was performed during 8 weeks. Thereafter, spinal cords were processed for immunohistochemistry. RESULTS: The animals of the moderate injury group in comparison with mild injury had a greater motor function deficit, worse mechanical allodynia, and latter bladder recovery; moreover, histological analysis revealed more extensive lesions with lower neuronal population. CONCLUSIONS: Our study suggests that moderate SCI causes a progressive and long-lasting painful condition (at least 8 weeks), in addition to motor impairment, and thus represents a reliable animal model for the study of chronic neuropathic pain after SCI.

Neurophysiological Effects of Dorsal Root Ganglion Stimulation (DRGS) in Pain Processing at the Cortical Level.

OBJECTIVES: Dorsal root ganglion stimulation (DRGS) has been used successfully against localized neuropathic pain. Nevertheless, the effects of DRGS on pain processing, particularly at the cortical level, remain largely unknown. In this study, we investigated whether positive responses to DRGS treatment would alter patients' laser-evoked potentials (LEP). METHODS: We prospectively enrolled 12 adult patients with unilateral localized neuropathic pain in the lower limbs or inguinal region and followed them up for six months. LEPs were assessed at baseline, after one month of DRGS, and after six months of DRGS. Clinical assessment included the Numerical Rating Scale (NRS), Brief Pain Inventory (BPI), SF-36, and Beck Depression Inventory (BDI). For each patient, LEP amplitudes and latencies of the N2 and P2 components on the deafferented side were measured and compared to those of the healthy side and correlated with pain intensity, as measured with the NRS. RESULTS: At the one- and six-month follow-ups, N2-P2 amplitudes were significantly greater and NRS scores were significantly lower compared with baseline (all p's < 0.01). There was a negative correlation between LEP amplitudes and NRS scores (rs = -0.31, p < 0.10). CONCLUSIONS: DRGS is able to restore LEPs to normal values in patients with localized neuropathic pain, and LEP alterations are correlated with clinical response in terms of pain intensity.

Prolonged Temozolomide Maintenance Therapy in Newly Diagnosed Glioblastoma.

BACKGROUND: The impact of prolonging temozolomide (TMZ) maintenance beyond six cycles in newly diagnosed glioblastoma (GBM) remains a topic of discussion. We investigated the effects of prolonged TMZ maintenance on progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: In this retrospective single-center cohort study, we included patients with GBM who were treated with radiation therapy with concomitant and adjuvant TMZ. For analysis, patients were considered who either completed six TMZ maintenance cycles (group B), continued with TMZ therapy beyond six cycles (group C), or stopped TMZ maintenance therapy within the first six cycles (group A). Patients with progression during the first six TMZ maintenance cycles were excluded. RESULTS: Clinical data from 107 patients were included for Kaplan-Meier analyses and 102 for Cox regressions. Median PFS times were 8.1 months (95% confidence interval [CI] 6.1-12.4) in group A, 13.7 months (95% CI 10.6-17.5) in group B, and 20.9 months (95% CI 15.2-43.5) in group C. At first progression, response rates of TMZ/lomustine rechallenge were 47% in group B and 13% in group C. Median OS times were 12.7 months (95% CI 10.3-16.8) in group A, 25.2 months (95% CI 17.7-55.5) in group B, and 28.6 months (95% CI 24.4-open) in group C. Nevertheless, multivariate Cox regression for patients in group C compared with group B that accounted for imbalances of other risk factors showed no different relative risk (RR) for OS (RR 0.77, p = .46). CONCLUSION: Our data do not support a general extension of TMZ maintenance therapy beyond six cycles. The Oncologist 2017;22:570-575 IMPLICATIONS FOR PRACTICE: Radiation therapy with concomitant and adjuvant temozolomide (TMZ) maintenance therapy is still the standard of care in patients below the age of 65 years in newly diagnosed glioblastoma. However, in clinical practice, many centers continue TMZ maintenance therapy beyond six cycles. The impact of this continuation is controversial and has not yet been addressed in prospective randomized clinical trials. We compared the effect of more than six cycles of TMZ in comparison with exactly six cycles on overall survival (OS) and progression-free survival (PFS) by multivariate analysis and found a benefit in PFS but not OS. Thus, our data do not suggest prolonging TMZ maintenance therapy beyond six cycles, which should be considered in neurooncological practice.

Dorsal Root Ganglion Stimulation Used for the Treatment of Chronic Neuropathic Pain in the Groin: A Single-Center Study With Long-Term Prospective Results in 34 Cases.

OBJECTIVE: Chronic neuropathic pain in the groin is a severe condition and difficult to treat. Dorsal root ganglion stimulation (DRGS) covers discrete painful areas precisely with its stimulation power in comparison to spinal cord stimulation (SCS). It was our hypothesis that DRGS provides a long-term relief of chronic groin pain over a period of more than three years. MATERIALS AND METHODS: Patients (age >18 years) with chronic neuropathic groin pain were prospectively examined. After a successful test-trial (duration of 3-10 days, pain decrease >50%) a permanent generator was implanted. The patients were re-examined after three months, then after one year, two, and three years. We used the Visual Analogue Scale (VAS), the Pain Disability Index (PDI), the Pain Catastrophizing Scale (PCS), the Brief Pain Inventory (BPI), and the Beck Depression Inventory (BDI) for the assessment. RESULTS: We included 34 consecutive patients (13 female, 21 male, mean age 50.4 years, range of age 24-84 years, 30/34 trial to permanent conversion) during the time period from 2012 until 2016. Thirty patients had a successful test-trial and a generator was subsequently implanted. Results after three years: the preoperative VAS dropped from Mdn = 8 to Mdn = 4.5 (p = 0.001). The PDI decreased from Mdn = 48 to Mdn = 23 (p = 0.004). The PCS changed from Mdn = 31 to Mdn = 16 (p = 0.006). The BPI dropped from Mdn = 76 to Mdn = 30 (p = 0.003). The BDI decreased from Mdn = 17 to Mdn = 7 (p = 0.010). Five patients showed complications (16.7%). CONCLUSION: In this study, DRGS proved an efficient long-term method for the treatment of chronic neuropathic groin pain and we strongly recommend its use.

Intraoperative assistive technologies and extent of resection in glioma surgery: a systematic review of prospective controlled studies.

Several studies published to date about glioma surgery have addressed the validity of using novel technologies for intraoperative guidance and potentially improved outcomes. However, most of these reports are limited by questionable methods and/or by their retrospective nature. In this work, we performed a systematic review of the literature to address the impact of intraoperative assistive technologies on the extent of resection (EOR) in glioma surgery, compared to conventional unaided surgery. We were also interested in two secondary outcome variables: functional status and progression-free survival. We primarily used PubMed to search for relevant articles. Studies were deemed eligible for our analysis if they (1) were prospective controlled studies; (2) used EOR as their primary target outcome, assessed by MRI volumetric analysis; and (3) had a homogeneous study population with clear inclusion criteria. Out of 493 publications identified in our initial search, only six matched all selection criteria for qualitative synthesis. Currently, the evidence points to 5-ALA, DTI functional neuronavigation, neurophysiological monitoring, and intraoperative MRI as the best tools for improving EOR in glioma surgery. Our sample and conclusions were limited by the fact that studies varied in terms of population characteristics and in their use of different volumetric analyses. We were also limited by the low number of prospective controlled trials available in the literature. Additional evidence-based high-quality studies assessing cost-effectiveness should be conducted to better determine the benefits of intraoperative assistive technologies in glioma surgery.

Evaluating cerebellar dentatotomy for the treatment of spasticity with or without dystonia.

Spasticity represents a common and very often incapacitating neurologic condition, for which a limited number of treatment options are available. Stereotactic ablation of the dentate cerebellar nuclei (dentatotomy) was widely used in the past with variable results. In the present study, we reviewed 12 consecutive cases operated on at the Midland Centre for Neurosurgery and Neurology at Birmingham University (Smetwick, UK) in the 1980s. The following clinical aspects were analyzed: severity of spasticity, occurrence of abnormal movements (dystonia/athetosis), language fluency, gait, and overall clinical condition. Follow-up ranged from 0.5 to 94 (mean: 31.6) months. Immediate improvement was noted in 10 patients, and five of them had sustained this improvement at the time of the last assessment. A more pronounced improvement was observed for gait, relative to speech and abnormal movements. No significant morbidity related to the procedure was observed. We conclude that dentatotomy is a safe procedure that should still be considered in specific cases. Here, we review the cases reported in the literature, and present a mechanistic hypothesis about how dentatotomy influences motor tonus, in light of the current knowledge about cerebellar physiology. We believe that this issue is critical for the development of alternative surgical approaches targeting the cerebellum, such as chronic electric stimulation.

Microsurgical reconstruction of the cauda equina after traumatic transecting injury.

INTRODUCTION: The microsurgical reconstruction of the cauda equina nerve roots (MRCER) after traumatic injury is a highly controversial procedure with very few reports in the literature. METHODS: We report on four patients who had a penetrating traumatic injury in the lumbosacral area and underwent primary MRCER at our institution during the last decade. RESULTS: All four patients presented complete distal sensory and motor palsy affecting the lower lumbosacral roots. Primary microsuture was feasible in three patients harboring stab wounds, whereas autologous nerve graft interposition was necessary in the patient who had a gunshot wound. At the 5-year follow-up, we observed a marked improvement in motor function in two patients, but no sensory recovery.

Combined spinal cord and peripheral nerve field stimulation for persistent post-herniorrhaphy pain.

OBJECTIVES: Chronic post-hernia pain is a common complication after inguinal herniorrhaphies. Peripheral nerve field stimulation (PNFS) and spinal cord stimulation (SCS) are two new promising treatment modalities. Four patients with persistent neuropathic post-hernia pain were recruited for this prospective study. MATERIALS AND METHODS: Electrodes were inserted into the epidural space of the spinal canal and into the subcutaneous tissue in the inguinal region during a single surgical procedure. During a 14-day trial, double-blind stimulation was performed via an external stimulator: three days using the spinal electrode (SCS), three days using the inguinal electrode (PNFS), three days using both (SCS + PNFS), and five days off, with an alternating order from patient to patient. During the trial, pain intensity was assessed thrice daily by the visual analog scale. Additionally, pain intensity and quality of life (QOL) were assessed before and after surgical intervention by the Brief Pain Inventory, SF36 scale, and Pain Disability Index. RESULTS: All patients had a marked pain reduction during the trial phase, and this reduction was more prominent when both electrodes were activated simultaneously (p < 0.001). At the late follow-up, a significant pain reduction and improvement of QOL was observed in three patients. CONCLUSIONS: Both SCS and PNFS are effective in treating post-hernia pain, but the magnitude of pain reduction was more prominent with concomitant stimulation. Combined PNFS and SCS should be considered for patients with a less than optimal response to either SCS or PNFS. More studies are necessary to address the cost-effect issues of this new approach to treatment.

Biomimetic Design of a Tendon-Driven Myoelectric Soft Hand Exoskeleton for Upper-Limb Rehabilitation.

Degenerative diseases and injuries that compromise hand movement reduce individual autonomy and tend to cause financial and psychological problems to their family nucleus. To mitigate these limitations, over the past decade, hand exoskeletons have been designed to rehabilitate or enhance impaired hand movements. Although promising, these devices still have limitations, such as weight and cost. Moreover, the movements performed are not kinematically compatible with the joints, thereby reducing the achievements of the rehabilitation process. This article presents the biomimetic design of a soft hand exoskeleton actuated using artificial tendons designed to achieve low weight, volume, and cost, and to improve kinematic compatibility with the joints, comfort, and the sensitivity of the hand by allowing direct contact between the hand palm and objects. We employed two twisted string actuators and Bowden cables to move the artificial tendons and perform the grasping and opening of the hand. With this configuration, the heavy part of the system was reallocated to a test bench, allowing for a lightweight set of just 232 g attached to the arm. The system was triggered by the myoelectric signals of the biceps captured from the user's skin to encourage the active participation of the user in the process. The device was evaluated by five healthy subjects who were asked to simulate a paralyzed hand, and manipulate different types of objects and perform grip strength. The results showed that the system was able to identify the intention of movement of the user with an accuracy of 90%, and the orthosis was able to enhance the ability of handling objects with gripping force up to 1.86 kgf.

Adjuvant Vaccination with Allogenic Dendritic Cells Significantly Prolongs Overall Survival in High-Grade Gliomas: Results of a Phase II Trial.

Immunotherapy for cancer treatment has gained increased attention in recent years. Recently, our group reported the case of a patient with glioblastoma who underwent vaccination based on dendritic cells and experienced a strong Th1 immune response together with near-complete tumor remission. Here we report the results of a phase I/II prospective, non-controlled clinical trial with 37 patients harboring glioblastoma or grade 4 astrocytomas. At the time of first recurrence after surgery, patients began receiving monthly intradermal injections of allogenic DC-autologous tumor cell hybridomas. Overall survival, quality of life, and immunological profiles were assessed prospectively. Compared with patients in the Genomic Data Commons data bank, overall survival for vaccinated patients with glioblastoma was 27.6 ± 2.4 months (vs. 16.3 ± 0.7, log-rank p < 0.001, hazard ratio 0.53, 95%CI 0.36-0.78, p < 0.01), and it was 59.5 ± 15.9 for vaccinated astrocytoma grade 4 patients (vs. 19.8 ± 2.5, log-rank p < 0.05, hazard ratio 0.18, 95%CI 0.05-0.62, p < 0.01). Furthermore, seven vaccinated patients (two IDH-1-mutated and five wild type) remain alive at the time of this report (overall survival 47.9 months, SD 21.1, range: 25.4-78.6 months since diagnosis; and 34.2 months since recurrence, range: 17.8 to 40.7, SD 21.3). We believe that the data reported here can foster the improvement of treatment protocols for high-grade gliomas based on cellular immunotherapy.

What Does the General Public Know (or Not) About Neuroscience? Effects of Age, Region and Profession in Brazil.

The field of Neuroscience has experienced a growing interest in recent decades, which has led to an exponential growth in the amount of related information made available online as well as the market for Neuroscience-related courses. While this type of knowledge can be greatly beneficial to people working in science, health and education, it can also benefit individuals in other areas. For example, neuroscience knowledge can help people from all fields better understand and critique information about new discoveries or products, and even make better education- and health-related decisions. Online platforms are fertile ground for the creation and spread of fake information, including misrepresentations of scientific knowledge or new discoveries (e.g., neuromyths). These types of false information, once spread, can be difficult to tear down and may have widespread negative effects. For example, even scientists are less likely to access retractions of peer-reviewed articles than the original discredited articles. In this study we surveyed general knowledge about neuroscience and the brain among volunteers in Brazil, Latin America's largest country. We were interested in evaluating the prevalence of neuromyths in this region, and test whether knowledge/neuromyth endorsement differs by age, region, and/or profession. To that end, we created a 30-item survey that was anonymously answered online by 1128 individuals. While younger people (20-29-year-olds) generally responded more accurately than people 60 and older, people in the North responded significantly worse than those in the South and Southeast. Most interestingly, people in the biological sciences consistently responded best, but people in the health sciences responded no better than people in the exact sciences or humanities. Furthermore, years of schooling did not correlate with performance, suggesting that quantity may surpass quality when it comes to extension or graduate-level course offerings. We discuss how our findings can help guide efforts toward improving access to quality information and training in the region.

Neuroscience Knowledge and Endorsement of Neuromyths among Educators: What Is the Scenario in Brazil?

The field of neuroscience has seen significant growth and interest in recent decades. While neuroscience knowledge can benefit laypeople as well as professionals in many different areas, it may be particularly relevant for educators. With the right information, educators can apply neuroscience-based teaching strategies as well as protect themselves and their students against pseudoscientific ideas and products based on them. Despite rapidly growing sources of available information and courses, studies show that educators in many countries have poor knowledge of brain science and tend to endorse education-related neuromyths. Poor English skills and fewer resources (personal, institutional and governmental) may be additional limitations in Latin America. In order to better understand the scenario in Latin America's largest country, we created an anonymous online survey which was answered by 1634 individuals working in education from all five regions of Brazil. Respondents stated whether they agreed with each statement and reported their level of confidence for each answer. Significant differences in performance were observed across regions, between educators living in capital cities versus the outskirts, between those teaching in private versus public schools, and among educators teaching different levels (pre-school up to college/university). We also observed high endorsement of some key neuromyths, even among groups who performed better overall. To the best of our knowledge, this is the first study to conduct a detailed analysis of the profile of a large group of educators in Brazil. We discuss our findings in terms of efforts to better understand regional and global limitations and develop methods of addressing these most efficiently.

Limited Ca2+ and PKA-pathway dependent neurogenic differentiation of human adult mesenchymal stem cells as compared to fetal neuronal stem cells.

The ability of mesenchymal stem cells to generate functional neurons in culture is still a matter of controversy. In order to assess this issue, we performed a functional comparison between neuronal differentiation of human MSCs and fetal-derived neural stem cells (NSCs) based on morphological, immunocytochemical, and electrophysiological criteria. Furthermore, possible biochemical mechanisms involved in this process were presented. NF200 immunostaining was used to quantify the yield of differentiated cells after exposure to cAMP. The addition of a PKA inhibitor and Ca(2+) blockers to the differentiation medium significantly reduced the yield of differentiated cells. Activation of CREB was also observed on MSCs during maturation. Na(+)-, K(+)-, and Ca(2+)-voltage-dependent currents were recorded from MSCs-derived cells. In contrast, significantly larger Na(+) currents, firing activity, and spontaneous synaptic currents were recorded from NSCs. Our results indicate that the initial neuronal differentiation of MSCs is induced by cAMP and seems to be dependent upon Ca(2+) and the PKA pathway. However, compared to fetal neural stem cells, adult mesenchymal counterparts are limited in their neurogenic potential. Despite the similar yield of neuronal cells, NSCs achieved a more mature functional state. Description of the underlying mechanisms that govern MSCs' differentiation toward a stable neuronal phenotype and their limitations provides a unique opportunity to enhance our understanding of stem cell plasticity.