A randomized phase 2b efficacy study in patients with seizure episodes with a predictable pattern using Staccato® alprazolam for rapid seizure termination.

OBJECTIVE: Alprazolam administered via the Staccato® breath-actuated device is delivered into the deep lung for rapid systemic exposure and is a potential therapy for rapid epileptic seizure termination (REST). We conducted an inpatient study (ENGAGE-E-001 [NCT03478982]) in patients with stereotypic seizure episodes with prolonged or repetitive seizures to determine whether Staccato alprazolam rapidly terminates seizures in a small observed population after administration under direct supervision. METHODS: Adult patients with established diagnosis of focal and/or generalized epilepsy with a documented history of seizure episodes with a predictable pattern were enrolled. They were randomized 1:1:1 to double-blind treatment of a single seizure event with one dose of Staccato alprazolam 1.0 mg or 2.0 mg, or Staccato placebo in an inpatient unit. The primary end point of the study was the proportion of responders in each treatment group achieving seizure activity cessation within 2 min after administration of study drug and no recurrence of seizure activity within 2 h. RESULTS: A total of 273 patients were screened, and 116 randomized patients received treatment with the study drug in the double-blind part. The proportion of treated patients who were responders was 65.8% for each of Staccato alprazolam 1.0 mg (n = 38; p = .0392) and 2.0 mg (n = 38; p = .0392), compared with 42.5% for Staccato placebo (n = 40). Staccato alprazolam was well tolerated when administered as a single dose of 1.0 or 2.0 mg: cough and somnolence were the most common adverse events (AEs) (both 14.5%), followed by dysgeusia (13.2%). AEs were mostly mild or moderate in intensity; there were no treatment-related serious AEs. SIGNIFICANCE: Both 1.0 mg and 2.0 mg doses of Staccato alprazolam demonstrated efficacy in rapidly terminating seizures in an inpatient setting and were well tolerated. The next step is a Phase 3 confirmatory study to demonstrate efficacy and safety of Staccato alprazolam for rapid cessation of seizures in an outpatient setting.

The use of e-consent in surgery and application to neurosurgery: a systematic review and meta-analysis.

INTRODUCTION: The integration of novel electronic informed consent platforms in healthcare has undergone significant growth over the last decade. Adoption of uniform, accessible, and robust electronic online consenting applications is likely to enhance the informed consent process and improve the patient experience and has the potential to reduce medico-legal ramifications of inadequate consent. A systematic review and meta-analysis was conducted to evaluate the utility of novel electronic means of informed consent in surgical patients and discuss its application to neurosurgical cohorts. METHODS: A review of randomised controlled trials, non-randomised studies of health interventions, and single group pre-post design studies in accordance with the PRISMA statement. Random effects modelling was used to estimate pooled proportions of study outcomes. Patient satisfaction with the informed consent process and patients' gain in knowledge were compared for electronic technologies versus non-electronic instruments. A sub-group analysis was conducted to compare the utility of electronic technologies in neurosurgical cohorts relative to other surgical patients in the context of patient satisfaction and knowledge gain. RESULTS: Of 1042 screened abstracts, 63 studies were included: 44 randomised controlled trials (n = 4985), 4 non-randomised studies of health interventions (n = 387), and 15 single group pre-post design studies (n = 872). Meta-analysis showed that electronic technologies significantly enhanced patient satisfaction with the informed consent process (P < 0.00001) and patients' gain in knowledge (P < 0.00001) compared to standard non-electronic practices. Sub-group analysis demonstrated that neurosurgical patient knowledge was significantly enhanced with electronic technologies when compared to other surgical patients (P = 0.009), but there was no difference in patient satisfaction between neurosurgical cohorts and other surgical patients with respect to electronic technologies (P = 0.78). CONCLUSIONS: Novel electronic technologies can enhance patient satisfaction and increase patients' gain in knowledge of their surgical procedures. Electronic patient education tools can significantly enhance patient knowledge for neurosurgical patients. If used appropriately, these modalities can shorten and/or improve the consent discussion, streamlining the surgical process and improving satisfaction for neurosurgical patients.

Spinal anaplastic ganglioglioma.

Anaplastic gangliogliomas of the spinal cord are extremely rare with only four cases reported in the literature. Here we present the case of a 22-year-old female who presented acutely with quadraparesis and urinary retention. Radiographic imaging demonstrated an intramedullary lesion within the cervical spine. She underwent a cervical laminectomy and resection of the lesion under neurophysiological monitoring. Post-operatively, she regained some function, but remained paraparetic. Histopathology demonstrated an anaplastic ganglioglioma (WHO Grade 3). She subsequently underwent radiotherapy. Following surgery, she remained stable and had MRC Grade 3 Power in all four limbs. Herein, we describe a previously undescribed case of cervical anaplastic ganglioglioma and review the existing literature.

Validation and improvement of a multiplex PCR method to detect murine Helicobacter species in feces samples of mice.

BACKGROUND: Murine Helicobacter species have gained increasing awareness in mouse facilities over the last years. Infections with Helicobacter species may have an impact effect on the health of mice and might pose a zoonotic risk to researchers. To minimize the interference with experiments and hence contribute to the 3Rs, a reliable method of monitoring Helicobacter infections in animal facilities needs to be available. The aim of this study was to improve and validate the detection of the most common murine Helicobacter species. MATERIAL AND METHODS: A multiplex PCR assay was developed for identification of Helicobacter hepaticus, H. bilis, H. muridarum, H. rodentium, and H. typhlonius that could simultaneously detect these five strains in fecal samples. To ensure the quality of the results, the method was validated based on recommendations for in-house developed tests. RESULTS: The method established was highly sensitive and specific. All five strains were detectable with a detection limit of 102 bacteria. Eight different mouse facilities were tested with the validated assay, and the following prevalence were found: H. rodentium 57%, H. hepaticus 46%, H. typhlonius 17%, H. bilis 12%, and H. muridarum 0%. CONCLUSION: The multiplex PCR is a reliable, economic, and time-saving diagnostic tool for routine health monitoring. Further prevalence studies are needed to confirm the high prevalence and hence importance of H. rodentium, as until now this agent is not yet listed in FELASA recommendations.

Enhancement of critical-sized bone defect regeneration using UiO-66 nanomaterial in rabbit femurs.

BACKGROUND: Repair of large-sized bone defects is a challengeable obstacle in orthopedics and evoked the demand for the development of biomaterials that could induce bone repair in such defects. Recently, UiO-66 has emerged as an attractive metal-organic framework (MOF) nanostructure that is incorporated in biomedical applications due to its biocompatibility, porosity, and stability. In addition, its osteogenic properties have earned a great interest as a promising field of research. Thus, the UiO-66 was prepared in this study and assessed for its potential to stimulate and support osteogenesis in vitro and in vivo in a rabbit femoral condyle defect model. The nanomaterial was fabricated and characterized using x-ray diffraction (XRD) and transmission electron microscopy (TEM). Afterward, in vitro cytotoxicity and hemolysis assays were performed to investigate UiO-66 biocompatibility. Furthermore, the material in vitro capability to upregulate osteoblast marker genes was assessed using qPCR. Next, the in vivo new bone formation potential of the UiO-66 nanomaterial was evaluated after induction of bone defects in rabbit femoral condyles. These defects were left empty or filled with UiO-66 nanomaterial and monitored at weeks 4, 8, and 12 after bone defect induction using x-ray, computed tomography (CT), histological examinations, and qPCR analysis of osteocalcin (OC) and osteopontin (OP) expressions. RESULTS: The designed UiO-66 nanomaterial showed excellent cytocompatibility and hemocompatibility and stimulated the in vitro osteoblast functions. The in vivo osteogenesis was enhanced in the UiO-66 treated group compared to the control group, whereas evidence of healing of the treated bone defects was observed grossly and histologically. Interestingly, UiO-66 implanted defects displayed a significant osteoid tissue and collagen deposition compared to control defects. Moreover, the UiO-66 nanomaterial demonstrated the potential to upregulate OC and OP in vivo. CONCLUSIONS: The UiO-66 nanomaterial implantation possesses a stimulatory impact on the healing process of critical-sized bone defects indicating that UiO-66 is a promising biomaterial for application in bone tissue engineering.

Presentation and management of spinal meningioma and its association with breast carcinoma-case series and systematic review.

OBJECTIVE: Benign spinal intradural tumors are rare entities and there have been relatively few case series describing the epidemiology and characteristics of these tumors. Here, we evaluate the presentation, demographics, pathology and outcomes associated with the surgical management of spinal meningioma in our unit over a 6-year period. RESULTS: A total of 68 cases presented to the operating surgeon during a 6-year period. Of these, over 80% (n = 55) were in females. Seventy-nine percent of the meningiomas were observed in the thoracic region (n = 54). Weakness and gait disturbance were the most common presenting complaints. Surgery significantly improved both motor outcome (p < 0.001) and health related qualities of life (SF36, p < 0.01).Seventeen percent of spinal meningioma cases (n = 12) had a preceding cancer diagnosis. Of these 75% (n = 9/12) were attributable to breast cancer. Overall, breast cancer preceded a diagnosis of a spinal meningioma in 16.4% of female cases (9/55). This is higher than expected number of breast cancer based on UK population and those reported in literature for breast cancer and intracranial meningioma. CONCLUSION: Spinal meningioma is disproportionately over-represented in females. Patients present with neurological deficits and surgery improved both neurology and patient reported quality of life. Relative to the known UK prevalence of breast cancer, there is a significantly higher than expected association between spinal meningioma and a preceding history of breast cancer.

Virtual planning of the anterolateral thigh free flap for heel reconstruction.

PURPOSE: three dimensional (3-D) virtual planning is an example of computer assisted surgery that improved management of composite tissue defects. However, converting the 3-D construct into two dimensional format is challenging. The purpose of this study was to assess 3-D virtual planning of complex heel defects for better optimized reconstruction. PATIENTS AND METHODS: a prospective analysis of 10 patients [9 male and 1 female; mean age = 27.9 years] with post-traumatic heel defects was performed. Heel defects comprised types II (three patients) or III (seven patients) according to Hidalgo and Shaw and were managed using anterolateral thigh (ALT) free flap adopting 3-D virtual planning of the actual defect which was converted into a silicone two dimensional mold. The mean definitive size of the defects was 63.4 cm3 . Functional, aesthetic, and sensory evaluations of both donor and recipient sites were performed 1 year after surgery. RESULTS: Six patients received thinned ALT (mean size = 139 cm3 ) while four patients received musculofasciocutaneous ALT flap (mean size = 199 cm3 ). One flap exhibited partial skin flap necrosis. Another flap was salvaged after re-exploration secondary to venous congestion. The mean follow-up was 20.2 months. The Maryland foot score showed 4 excellent, 5 good, and 1 fair cases. The mean American Orthopedic Foot and Ankle hind foot scoring was 76.3 (range: 69-86). All patients regained their walking capability. CONCLUSIONS: 3-D virtual planning of complex heel defects facilitates covering non-elliptical defects while harvesting a conventional elliptical flap with providing satisfactory functional outcomes and near-normal contour, volume, and sensibility.

Differences in management of isolated spinal fractures between neurosurgery and orthopaedics: a 6-year retrospective study.

INTRODUCTION: The acute management of spinal fractures is traditionally split between neurosurgeons and orthopaedic surgeons and the specialities have varying approaches to management. This study investigates differences between neurosurgeons and spinal orthopaedic surgeons in the management of spinal fractures at a single trauma centre in the United Kingdom. METHODS: A retrospective study at a single trauma centre of patients identified using the Trauma Audit and Research Network (TARN). Case notes and radiological investigations were reviewed for demographics, fracture classification, clinical management and outcomes. Polytrauma cases and patients managed by non-neurosurgical/orthopaedic specialties were excluded. RESULTS: A total of 465 patients were included in this study (neurosurgery n = 266, orthopaedics n = 199). There were no significant differences between groups for age, gender, Charlson co-morbidity score or distribution of fractures using the AO spine classification. Patients admitted and managed under the orthopaedic surgeons were more likely to undergo a surgical procedure when compared to those admitted under the neurosurgeons (n = 71; 35.7% vs n = 71; 26.8%, p = 0.042, OR 1.56 95%CI 1.056 to 2.31). The median overall length of stay was 8 days and there was no significant difference between teams; however, the neurosurgical cohort were more likely to be admitted to an intensive care unit (24.3% vs 16.2%, p = 0.04). CONCLUSION: This study is the first in the United Kingdom to compare neurosurgical and orthopaedic teams in their management of spinal fractures. It demonstrates that differences may exist both in operating rates and outcomes.

Comparison between long and lower medial head triceps branches in dual neurotization for shoulder function restoration in upper brachial plexus palsy.

PURPOSE: In upper brachial plexus injury (UBPI), restoring shoulder function is crucial. This study compares the transfer of long and lower medial heads of triceps branches to the axillary nerve to achieve proper restoration of function. PATIENTS AND METHODS: A retrospective comparative study was conducted between two groups of patients with (UBPI). Group I patients (10) [mean age: 19 ± 10.6 years] were managed by transferring triceps long head branch to axillary nerve while group II patients (8) [mean age: 26 ± 9.6 years] were managed by triceps lower medial head branch transfer. The mean time from injury to surgery was 6 ± 1.3 and 5 ± 1.7 months respectively. All patients were followed up for a minimum of 12 months with the assessment of VAS, DASH score, active range of motion (AROM) and strength of shoulder abduction and external rotation; in addition to shoulder endurance and strengths of donors. Postoperative, three-monthly, electrodiagnostic assessments were performed. RESULTS: Postoperatively, the mean VAS and DASH scores; in addition to endurance time, showed significant enhancement in both groups. Patients in both groups have accomplished a mean abduction (AROM) of 98° ± 27.9 and 97° ± 11.9 respectively. The mean external rotation (AROM) was 48° ± 18.4 and 47° ± 9.2 respectively. Furthermore, group II patients had less triceps morbidity in addition to earlier and enhanced electrophysiological recovery. CONCLUSIONS: Dual neurotization for shoulder function restoration in (UBPI) is capable of providing proper functional results with minimal donor morbidity. The triceps lower medial branch provides an excelling donor due to less triceps morbidity, extra length; yet, earlier and enhanced electrophysiological recovery.

Alternatively activated macrophages; a double-edged sword in allergic asthma.

BACKGROUND: Macrophages are heterogenous phagocytic cells with an important role in the innate immunity. They are, also, significant contributors in the adaptive immune system. Macrophages are the most abundant immune cells in the lung during allergic asthma, which is the most common chronic respiratory disease of both adults and children. Macrophages activated by Th1 cells are known as M1 macrophages while those activated by IL-4 and IL-13 are called alternatively activated macrophages (AAM) or M2 cells. AAM are subdivided into four distinct subtypes (M2a, M2b, M2c and M2d), depending on the nature of inducing agent and the expressed markers. BODY: IL-4 is the major effector cytokine in both alternative activation of macrophages and pathogenesis of asthma. Thus, the role of M2a macrophages in asthma is a major concern. However, this is controversial. Therefore, further studies are required to improve our knowledge about the role of IL-4-induced macrophages in allergic asthma, through precisive elucidation of the roles of specific M2a proteins in the pathogenesis of asthma. In the current review, we try to illustrate the different functions of M2a macrophages (protective and pathogenic roles) in the pathogenesis of asthma, including explanation of how different M2a proteins and markers act during the pathogenesis of allergic asthma. These include surface markers, enzymes, secreted proteins, chemokines, cytokines, signal transduction proteins and transcription factors. CONCLUSIONS: AAM is considered a double-edged sword in allergic asthma. Finally, we recommend further studies that focus on increased selective expression or suppression of protective and pathogenic M2a markers.

Randomized open-label trial of intravenous brivaracetam versus lorazepam for acute treatment of increased seizure activity.

OBJECTIVE: The objective of the present trial was to assess efficacy and safety of intravenous (IV) brivaracetam (BRV) vs. lorazepam (LZP) in patients with epilepsy undergoing evaluation in an epilepsy monitoring unit (EMU) who experienced seizures requiring acute treatment. METHODS: This was a phase 2, open-label, randomized, active-control, proof-of-concept trial (EP0087; NCT03021018). Patients (18-70 years) admitted to EMU were randomized 1:1:1 to single-dose bolus IV LZP (dose per investigator's practice), IV BRV 100 mg, or IV BRV 200 mg. Trial medication had to be administered within 30 min of qualifying seizure. Primary efficacy outcome was time to next seizure (clinical observation with electroencephalogram [EEG] confirmation) or to rescue medication use within 12 h of trial medication administration. Secondary outcomes included seizure freedom and rescue medication use within 12 h of trial medication administration. Safety and tolerability outcomes included treatment-emergent adverse events (TEAEs). RESULTS: Overall, 46 patients were randomized, and 45 received trial medication for a qualifying seizure. Patients in the LZP arm had doses from 1 to 4 mg (median: 1 mg). Eleven of 45 patients had a seizure within 12 h of trial medication administration (LZP 5/15 [median time to next seizure: 5.55 h], BRV 100 mg 3/15 [5.97 h], BRV 200 mg 3/15 [3.60 h]). No patients received additional rescue medication to control their qualifying seizure. Most patients were seizure-free over 12 h (LZP 9/15 [60.0%], BRV 100 mg 12/15 [80.0%], BRV 200 mg 12/15 [80.0%]). Rescue medication use within 12 h was numerically higher for LZP (6/15 [40.0%]) vs. BRV 100 mg (1/15 [6.7%]) and vs. BRV 200 mg (2/15 [13.3%]). Treatment-emergent adverse events were reported by 5/16 (31.3%), 6/15 (40.0%), and 3/15 (20.0%) of LZP, BRV 100 mg, and BRV 200 mg patients; one LZP patient had a serious TEAE (seizure cluster). Most common TEAEs (≥10% of patients) were sedation and somnolence with LZP, and dizziness, headache, and nausea with BRV. SIGNIFICANCE: Intravenous LZP, IV BRV 100 mg, and IV BRV 200 mg showed similar efficacy in controlling acute seizure activity in the EMU. Treatment-emergent adverse events were as expected for each medication. Although this trial should be interpreted with caution because of small patient numbers, it suggests a possible role of BRV in the acute treatment of increased seizure activity.

Neurosurgical management of head injuries incurred during sports: a single centre experience.

Introduction: Accidents during sporting activities are a common cause of head injury, particularly in children and young adults. Whilst most sporting head injuries are minor, there remains a proportion which is associated with high morbidity and mortality. The epidemiology of sports associated head injuries is variable based on geographical region so the aim of this study was to review the management and outcomes of sporting head injuries managed by a single neurosurgical unit in the South of England.Method: A retrospective review of the Trauma Audit and Research Network database was conducted for all patients admitted to a tertiary neurosurgical centre over a six-year period (January 2011-December 2016). Case notes were reviewed for demographics, mechanism of injury, injury severity score, intensive care admission, surgical interventions and Glasgow Outcome Score at discharge.Results: Seventy-six patients (mean age: 37.6 ± 18.4 years, male gender n = 43; 56.6%) were eligible for inclusion in this series. Horse riding accidents were identified as the most common cause of head injury (n = 31; 40.8%). Fifteen patients (19.7%) in this series had a severe head injury (GCS 3-8 on admission). Twenty-eight (36.8%) patients required admission to an intensive care unit and 26 (34.2%) patients underwent neurosurgical intervention. At discharge, 68 (89.5%) patients had a Glasgow Outcome Score 4-5.Conclusion: The majority of patients with head injuries admitted to a neurosurgical unit can expect a good functional outcome despite the need for intensive care or neurosurgical intervention. The range of sports resulting in head injury is likely influenced by geographic location; however, further national study is required for wider comparison.

Combined subtalar distraction arthrodesis with peroneus brevis tenotomy for posttraumatic subtalar arthritis.

BACKGROUND: Subtalar distraction arthrodesis is advocated as a salvage procedure for isolated posttraumatic subtalar arthritis. This study aimed at evaluating combined subtalar distraction arthrodesis with peroneus brevis tenotomy for such cases. METHODS: Twenty patients with isolated posttraumatic subtalar arthritis managed by combined subtalar distraction arthrodesis and peroneus brevis tenotomy were reviewed for a retrospective study. The American orthopaedic foot and ankle society [AOFAS] hindfoot scoring, talocalcaneal height [TCH], talocalcaneal angle [TCA] and heel valgus angle [HVA] were used for both pre and postoperative assessments. RESULTS: The mean postoperative [TCH] [70.3±1.9mm] was statistically better than the preoperative value [64.7±2.2mm] [p<0.001]. There was a statistically significant decrease in [HVA] [p<0.001]. On the contrary, there was a statistically significant increase in both [AOFAS] hindfoot scoring and the [TCA] [p<0.001]. CONCLUSIONS: Applying this technique for isolated posttraumatic subtalar arthritis with peroneal tendinitis improved both lateral retromalleolar swelling and deformity correction.

Association of aortic vascular uptake of 18FDG by PET/CT and aortic wall thickness by MRI in psoriasis: a prospective observational study.

BACKGROUND: The contribution of inflammation to the incidence of cardiovascular disease (CVD) has been increasingly recognized in recent years. We investigated the relationship of aortic vascular uptake of 18F-FDG by PET/CT and aortic wall thickness (AWT) by MRI in psoriasis, a chronic inflammatory disease with increased incidence of CVD. One hundred sixty-five patients with plaque psoriasis participated in an ongoing longitudinal cohort study. Subclinical atherosclerosis was assessed as aortic uptake of 18F-FDG by PET/CT reported as target-to-background ratio (TBR) and AWT by MRI reported as maximal thickness. RESULTS: Patients with psoriasis were middle aged, predominantly male, and had mild CV risk by traditional risk factors. Psoriasis severity as measured by PASI score was a notable determinant of AWT (ρ = 0.20, p = 0.01). Moreover, aortic vascular uptake of 18F-FDG associated with AWT by MRI at baseline in unadjusted analysis (ß = 0.27 p = 0.001) and following adjustment for traditional cardiovascular risk factors, waist-to-hip ratio, and statin use (ß = 0.21 p = 0.01). Finally, following 1 year of psoriasis treatment, a decrease in aortic vascular uptake of 18F-FDG was associated with a reduction in AWT in fully adjusted models (ß = 0.33, p = 0.02). CONCLUSION: In conclusion, we demonstrate that psoriasis severity and aortic vascular uptake of 18F-FDG in the aorta were associated with AWT. Following treatment of psoriasis, a decrease in aortic vascular uptake of 18F-FDG was associated with a reduction in AWT at 1 year. These findings suggest that aortic vascular uptake of 18F-FDG is associated with early evidence of vascular disease assessed by aortic wall thickness. Prospective studies in larger populations including other inflammatory diseases are warranted.

Lumbar intravertebral disc herniation secondary to idiopathic calcific discitis.

Calcific discitis is a well recognized entity in the paediatric population but more recently has been increasingly reported in adults. It typically involves the lower thoracic vertebrae and is of unknown aetiology. Herniation of the calcified fragment is rare but typically occurs out through the annulus fibrosus into the canal space. Herein we describe the first reported case of calcific discitis involving the lumbar vertebrae with subsequent herniation of the calcified disc into and through the anterior aspect of the L5 vertebra. The patient first presented with a history of right back pain and leg sciatica. Radiographic imaging demonstrated calcification within the L4/5 interspace, which was managed with simple analgesia. She subsequently re-presented 24-months later with worsening sciatica, right leg weakness and faecal incontinence. No evidence of cord or root compression was noted on MRI. However, an abnormality was noted at the anterior body of L5 with evidence of superior endplate depression and marrow signal change. Subsequent radionucleide bone studies confirmed a solitary focus of increased linear activity extending across the width of the L4-L5 interspace. Her symptoms were managed medically. Serial radiographic imaging demonstrated regression of the disc space calcification and healing of the L5 fracture. Despite its sinister presentation this condition was self-limiting. We describe the radiographic evolution of this pathology and postulate a putative hypothesis through which it may have arisen.

AMPA receptors and seizures mediate hippocampal radial glia-like stem cell proliferation.

Neurogenesis is sustained throughout life in the mammalian brain, supporting hippocampus-dependent learning and memory. Its permanent alteration by status epilepticus (SE) is associated with learning and cognitive impairments. The mechanisms underlying the initiation of altered neurogenesis after SE are not understood. Glial fibrillary acidic protein-positive radial glia (RG)-like cells proliferate early after SE, but their proliferation dynamics and signaling are largely unclear. We have previously reported a polarized distribution of AMPA receptors (AMPARs) on RG-like cells in vivo and postulated that these may signal their proliferation. Here, we examined the acute effects of kainate on hippocampal precursor cells in vitro and in kainate-induced SE on proliferating and quiescent clones of 5-bromo-2-deoxyuridine prelabeled hippocampal precursors in vivo. In vitro, we found that 5 µM kainate shortened the cell cycle time of RG-like cells via AMPAR activation and accelerated cell cycle re-entry of their progeny. It also shifted their fate choice expanding the population of RG-like cells and reducing the population of downstream amplifying neural progenitors. Kainate enhanced the survival of all precursor cell subtypes. Pharmacologically, kainate's proliferative and survival effects were abolished by AMPAR blockade. Functional AMPAR expression was confirmed on RG-like cells in vitro. In agreement with these observations, kainate/seizures enhanced the proliferation and expansion predominantly of constitutively cycling RG-like cell clones in vivo. Our results identify AMPARs as key potential players in initiating the proliferation of dentate RG-like cells and unravel a possible receptor target for modifying the radial glia-like cell response to SE.

Role of diffusion-weighted magnetic resonance imaging in the differentiation of benign and malignant pulmonary lesions.

PURPOSE: To evaluate the role of magnetic resonance (MRI) diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) measurement of solid and cystic pulmonary masses in differentiating benign from malignant lesions. MATERIAL AND METHODS: The study included 41 patients with pulmonary masses, who underwent conventional MRI and DWI (b value 0, 500, and 1000 s/mm²) examinations with 1.5-T MRI. The diffusion signal and the mean ADC values of the solid and cystic lesions were obtained. Statistical analyses were performed with the Mann-Whitney U test (z), Pearson's chi-square test, and receiver operating characteristic (ROC) analysis. RESULTS: Thirty-three lesions were malignant, and eight lesions were benign. The malignant masses showed significantly higher signal intensity on DWI than benign masses (p = 0.006), and the mean ADC value of malignant solid lesions was significantly lower than that of benign lesions (p = 0.02). By ROC analysis, an ADC cut-off value of 1.4 × 10-3 mm2/s was considered the threshold value, and the sensitivity and specificity were 93.8% and 75%, respectively. There was no significant difference between the ADC value of the cystic parts inside the benign and the malignant lesions. CONCLUSIONS: Diffusion-weighted MRI and measurement of ADC value can significantly differentiate between solid benign and malignant pulmonary masses.