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Spontaneous central nervous system (CNS) infections in children are rare. Treatment involves surgical intervention and antibiotic therapy. We describe a single centre experience of managing this condition in South Wales.We performed a retrospective review of surgically managed cases in our unit for patients under 18 years of age between 2008 and 2018. Data were collected regarding aetiology, location, microbiology examination, treatment and outcomes.Twenty-six patients were identified of which 25 case notes were available. Fifteen were male and 10 were female. Median age was 12 years (age range 0.3-17 years). Seven patients (28%) had a burr-hole aspiration and 18 (72%) underwent craniotomy. A second procedure was performed in 10 (40%) and a third procedure in two (8%). Fourteen (56%) had a brain abscess, 10 (40%) had subdural empyema (one was bilateral) and one (4%) had an extradural empyema. Fifteen (60%) had a raised WCC (11.5 × 10In Wales, outcomes have improved over time in keeping with other paediatric neurosurgical units in England. Increased availability of imaging resources in our hospital and use of neuro-navigation for all cases in our unit as well as earlier identification of sepsis, communication with microbiologists with dedicated ward rounds and, enhanced identification of causative organisms and contemporary anti-microbials have also contributed towards the improved management of this condition.

Introduction\udPosterior fossa (PF) tumours are associated with vasogenic oedema causing symptoms of raised intracranial pressure. Preoperatively this is managed with dexamethasone. To minimise steroid related complications, the lowest effective dose should be administered. No neurosurgical guidelines exist for pre-operative dosing of dexamethasone in PF tumours.\ud\udMethods\udA retrospective review was performed of surgically managed cases for patients under 16 years of age between 2013 and 2018 to ascertain the initial dose of dexamethasone with symptomatic PF tumours.\ud\udResults\udThirty-six patients were identified of which 30 notes were available. Sixteen were male. Median age was 6 years (range 10 months − 15 years). Twenty-two (73%) were referrals from DGH and 8 (27%) presented to our neurosurgical centre. All patients presented with symptomatic PF tumours including headache (97%), vomiting (93%), gait disturbance (43%), and nystagmus (17%). Four (13%) had papilloedema. Average initial stat dexamethasone dose was 9.15 mg; 0.31 mg/kg (range 1–16.7 mg; 0.05 − 1.77 mg/kg). Stratified according to weight, average dose (and range) was 8.8 mg; 0.94 mg/kg (1–16.6 mg; 0.13 − 1.77 mg/kg) in those weighing 30 kg up to a maximum of 16.6 mg in any 24h period. These results suggest that dosage was higher in those children weighing less. PPI was used in 24 (80%) of cases. All doses were reduced after review by the neurosurgical team and a PPI added.\ud\udConclusion\udPre-operative dexamethasone dosing does not always reflect the severity of clinical symptoms for PF tumours. Guidelines are required to correlate clinical symptoms with a suggested suitable dose of dexamethasone to prevent overdose and complications associated with corticosteroid use. We recommend a weight-based regimen as provided by the Food and Drug Administration. The current advice is for 0.02–0.3mg/kg/day in 3–4 divided doses

BACKGROUND To evaluate the surgical outcomes of arachnoid cyst decompression in patients less than 16 years of age with an associated neurodevelopmental disorder (NDD). METHODS A retrospective analysis of surgically treated congenital arachnoid cyst within South Wales between 2010-2019. Surgical outcomes are measured according to clinical (COG; clinical outcome score) and radiological (NOG; neuroimaging outcome score) outcomes and the complication profiles are described. The association between arachnoid cysts and NDD both in South Wales and the literature review cohort is also discussed. RESULTS The prevalence of congenital arachnoid cysts in South Wales is 0.02% and their association with neurodevelopmental disorders among patients with a congenital arachnoid cyst is high (estimated prevalence 19%). 18 (51%) in total were surgically treated in our unit; 7 with an associated NDD. All surgical modalities showed improved clinical and radiological outcomes in those with an associated neurodevelopmental disorder. 4 (15%) patients who had endoscopic treatment, and 2 (7%) of those who underwent craniotomy had complications. No complications following cystoperitoneal shunt were seen. 4 (21%) surgically treated patients were ultimately shunted following initial treatment by endoscopy or craniotomy. CONCLUSIONS In a cohort of patients diagnosed with a congenital arachnoid cyst in association with a neurodevelopmental disorder, all surgical treatments show improved clinical and radiological outcomes. Cystoperitoneal shunting appears to have a favourable complication profile.

Background Thirty-day readmission has become a significant health care metric reflecting the quality of care and on the cost of service delivery. There is little data on the impact of complications following skull base surgery (SBS) on emergency readmission. Identifying modifiable risk factors for readmission may improve care and reduce cost. Design The study was designed as a single-center retrospective cohort study. Methods Records for a consecutive series of 165 patients who underwent open or endoscopic SBS by a single surgeon reviewed. Patients with pituitary adenoma were excluded. The diagnosis, procedure, complications, length of stay (LOS), body mass index (BMI), and smoking status were recorded. Readmission to the neurosurgical department or regional hospitals was either noted prospectively or the patient contacted. Cause and length of readmission was documented. Results Of the 165 cases, 14 (8.5%) were readmitted within 30 days. Causes for readmission included cerebrospinal fluid (CSF) leak in 5/14 or 35.7% (overall rate for readmission for this complication in the series is 3.1%), infection in 4/14 (28.6%), hyponatraemia in 2/14 (14.3%), vascular: sinus thrombosis in 1/14 (7.1%), seizures in 1/14 (7.1%), and epistaxis in 1/14 (7.1%). Initial and readmission LOS was 6 and 14 days, respectively. BMI was higher in those readmitted within 30 days (33.2 kg/m2) versus no readmission (27.1 kg/m2). In addition, of those readmitted within 30 days, 35.7% were smokers compared with 20.8% in those not readmitted. Conclusion In this series, smoking and raised BMI may be indicators for within 30-day readmission and complications in this population, raising the question of risk factor modification prior to elective intervention.

Traumatic brain injury (TBI) poses a major public health problem on a global scale. Its burden results from high mortality and significant morbidity in survivors. This stems, in part, from an ongoing inadequacy in diagnostic and prognostic indicators despite significant technological advances. Traumatic axonal injury (TAI) is a key driver of the ongoing pathological process following TBI, causing chronic neurological deficits and disability. The science underpinning biomarkers of TAI has been a subject of many reviews in recent literature. However, in this review we provide a comprehensive account of biomarkers from animal models to clinical studies, bridging the gap between experimental science and clinical medicine. We have discussed pathogenesis, temporal kinetics, relationships to neuro-imaging, and, most importantly, clinical applicability in order to provide a holistic perspective of how this could improve TBI diagnosis and predict clinical outcome in a real-life setting. We conclude that early and reliable identification of axonal injury post-TBI with the help of body fluid biomarkers could enhance current care of TBI patients by (i) increasing speed and accuracy of diagnosis, (ii) providing invaluable prognostic information, (iii) allow efficient allocation of rehabilitation services, and (iv) provide potential therapeutic targets. The optimal model for assessing TAI is likely to involve multiple components, including several blood biomarkers and neuro-imaging modalities, at different time points.

Activation of Ras into the GTP-binding, 'ON' state is a key switch in the neurotrophin-mediated neuronal survival and neurite outgrowth, in vitro as well as in vivo. In the current study we explored changes in GTP-Ras levels following facial nerve injury and the ensuing regeneration and the effects of perturbing these changes in vivo using synapsin-promoter mediated neuronal expression of constitutively active Val12H-Ras (synRas). Quantification of GTP-Ras and total Ras revealed a precipitous drop in the relative GTP-Ras levels in the axotomized facial motor nucleus, to 40% of normal levels at 2 days after cut, followed by a partial recovery to 50-65% at 4-28 days. On western blots, control and axotomized nuclei from synRas mutants showed a 2.2- and 2.5-fold elevation in GTP-Ras, respectively, compared with their wild type littermate controls (p < 5%, anova, TUKEY post-hoc), with the levels in the axotomized synRas nucleus slightly but not significantly above that in the uninjured littermate control (p = 9.9%). Similar increase was also observed in the pERK but not pAKT targets of the Ras cascade. This moderate elevation of GTP-Ras strongly curtailed post-traumatic neuronal cell death (-65%), the influx of T-cells (-48%) as well as other parameters of neuroinflammatory response. Although synRas did not affect the speed of axonal regeneration or functional recovery it caused a very pronounced increase in central axonal sprouting. These current data emphasize the role of reduced active Ras, and by extension, the reduced overall level of retrograde neurotrophin signalling after axotomy, in mediating post-traumatic cell death and inflammation and in restricting the sprouting response. Moreover, the neuroprotective and central sprouting-enhancing effects of neuronal Val12H-Ras could help promote recovery in CNS injury.

Transforming growth factor beta1 (TGFbeta1) is a pleiotropic cytokine with potent neurotrophic and immunosuppressive properties that is upregulated after injury, but also expressed in the normal nervous system. In the current study, we examined the regulation of TGFbeta1 and the effects of TGFbeta1 deletion on cellular response in the uninjured adult brain and in the injured and regenerating facial motor nucleus. To avoid lethal autoimmune inflammation within 3 weeks after birth in TGFbeta1-deficient mice, this study was performed on a T- and B-cell-deficient RAG2-/- background. Compared with wild-type siblings, homozygous deletion of TGFbeta1 resulted in an extensive inflammatory response in otherwise uninjured brain parenchyma. Astrocytes increased in GFAP and CD44 immunoreactivity; microglia showed proliferative activity, expression of phagocytosis-associated markers [alphaXbeta2, B7.2, and MHC1 (major histocompatibility complex type 1)], and reduced branching. Ultrastructural analysis revealed focal blockade of axonal transport, perinodal damming of axonal organelles, focal demyelination, and myelin debris in granule-rich, phagocytic microglia. After facial axotomy, absence of TGFbeta1 led to a fourfold increase in neuronal cell death (52 vs 13%), decreased central axonal sprouting, and significant delay in functional recovery. It also interfered with the microglial response, resulting in a diminished expression of early activation markers [ICAM1 (intercellular adhesion molecule 1), alpha6beta1, and alphaMbeta2] and reduced proliferation. In line with axonal and glial findings in the otherwise uninjured CNS, absence of endogenous TGFbeta1 also caused an approximately 10% reduction in the number of normal motoneurons, pointing to an ongoing and potent trophic role of this anti-inflammatory cytokine in the normal as well as in the injured brain.

0.1 μm gate length GaAs pHEMT having gate peripheries of 2×25 μm (number of gate finger × unit gate width) is fabricated on the 2mil (50.8 μm) GaAs/AlGaAs/InGaAs substrate using PP10-10 process. This work presents a measurement based bias dependent model for a 2×25 μm GaAs pHEMT. Measurement includes pulsed I-V and on wafer scattering parameters for the frequency range of 45 MHz to 110 GHz. Comparison of measurement data and WIN foundry's process design kit (PDK) model is presented using Advanced Design System (ADS).

Peripheral nerve injury is normally followed by a robust regenerative response. Here we describe the early changes associated with injury from the initial rise in intracellular calcium and the subsequent activation of transcription factors and cytokines leading to an inflammatory reaction, and the expression of growth factors, cytokines, neuropeptides, and other secreted molecules involved in cell-to-cell communication promoting regeneration and neurite outgrowth. The aim of this review is to summarize the molecular mechanisms that play a part in executing successful regeneration.

The translocator protein (18 kDa; TSPO), formerly known as the peripheral benzodiazepine receptor, is an outer mitochondrial membrane protein that associates with the mitochondrial permeability transition pore to regulate both steroidogenesis and apoptosis. TSPO expression is induced in adult dorsal root ganglion (DRG) sensory neurons after peripheral nerve injury and a TSPO receptor ligand, Ro5-4864, enhances DRG neurite growth in vitro and axonal regeneration in vivo. We have now found that TSPO is induced in neonatal motor neurons after peripheral nerve injury and have evaluated its involvement in neonatal and adult sensory and motor neuron survival, and in adult motor neuron regeneration. The TSPO ligand Ro5-4864 rescued cultured neonatal DRG neurons from nerve growth factor withdrawal-induced apoptosis and protected neonatal spinal cord motor neurons from death due to sciatic nerve axotomy. However, Ro5-4864 had only a small neuroprotective effect on adult facial motor neurons after axotomy, did not delay onset or prolong survival in SOD1 mutant mice, and failed to protect adult DRG neurons from sciatic nerve injury-induced death. In contrast, Ro5-4864 substantially enhanced adult facial motor neuron nerve regeneration and restoration of function after facial nerve axotomy. These data indicate a selective sensitivity of neonatal sensory and motor neurons to survival in response to Ro5-4864, which highlights that survival in injured immature neurons cannot necessarily predict success in adults. Furthermore, although Ro5-4864 is only a very weak promoter of survival in adult neurons, it significantly enhances regeneration and functional recovery in adults.

Unlike its central counterpart, the peripheral nervous system is well known for its comparatively good potential for regeneration following nerve fiber injury. This ability is mirrored by the de novo expression or upregulation of a wide variety of molecules including transcription factors, growth-stimulating substances, cell adhesion molecules, intracellular signaling enzymes and proteins involved in regulating cell-surface cytoskeletal interactions, that promote neurite outgrowth in cultured neurons. However, their role in vivo is less known. Recent studies using neutralizing antibodies, gene inactivation and overexpression techniques have started to shed light on those endogenous molecules that play a key role in axonal outgrowth and the process of successful functional repair in the injured nervous system. The aim of the current review is to provide a summary on this rapidly growing field and the experimental techniques used to define the specific effects of candidate signaling molecules on axonal regeneration in vivo.

Peripheral nerve injury is normally followed by a robust regenerative response. Here we describe the early changes associated with injury from the initial rise in intracellular calcium and the subsequent activation of transcription factors and cytokines leading to an inflammatory reaction, and the expression of growth factors, cytokines, neuropeptides, and other secreted molecules involved in cell-to-cell communication promoting regeneration and neurite outgrowth. The aim of this review is to summarize the molecular mechanisms that play a part in executing successful regeneration.

Nerve injury triggers numerous changes in the injured neurons and surrounding nonneuronal cells that ultimately result in successful target reinnervation or cell death. c-Jun is a component of the heterodimeric AP-1 transcription factor, and c-Jun is highly expressed in response to neuronal trauma. Here we have investigated the role of c-jun during axonal regeneration using mice lacking c-jun in the central nervous system. After transection of the facial nerve, the absence of c-Jun caused severe defects in several aspects of the axonal response, including perineuronal sprouting, lymphocyte recruitment, and microglial activation. c-Jun-deficient motorneurons were atrophic, resistant to axotomy-induced cell death, and showed reduced target muscle reinnervation. Expression of CD44, galanin, and α7β1 integrin, molecules known to be involved in regeneration, was greatly impaired, suggesting a mechanism for c-Jun-mediated axonal growth. Taken together, our results identify c-Jun as an important regulator of axonal regeneration in the injured central nervous system.

We have previously reported in a model of spinal cord injury that the omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has signifi cant neuroprotective effects after trauma in the central nervous system [1]. In the present study we extend our observations on the neuroprotective and neuroregenerative effects of DHA to a peripheral nerve injury model. Facial nerve transection in mice is a well-established model used in studies on axonal regeneration [2]. We carried out this nerve lesion in mice and we studied the effects of oral supplementation with DHA after injury, on neuronal and glial markers of injury, and on neurological outcome. Female adult C57Bl6 mice (6 animals per group) were used throughout. Animals were placed for 1 week before surgery on a standard powdered diet. For the surgery, the right facial nerve, including the retroauricular branch, was transected at the styloid foramen under deep anaesthesia. After injury, mice continued to receive either the standard diet or a diet enriched with DHA (300 mg/kg/day), for 14 days. On the last day of treatment, the neurological outcome was assessed by measuring the movement of the whiskers, on a scale from 0 (no movement) to 3 (normal movement) [3]. Then the animals were killed and perfused intracardially with 4% paraformaldehyde. The brainstem was removed, post-fi xed and cryoprotected. 20 μm sections were cut at the level of the facial nucleus, and were incubated with primary antisera for calcitonin gene-related peptide (CGRP, 1:400, peninsula) and galanin (1:400, Peninsula), as neuronal markers, and for the integrin subunits αM (1:5000, Pharmingen) and β1 (1:3000, Pharmingen), whose expression is microglial only, and mixed neuronal/microglial, respectively. Total immunoreactivity for each antigen was quantifi ed in 2 sections per animal. Data was expressed as means ± SEM and analysed statistically using Student’s t test. In the DHA-treated group there was a signifi cant increase in the number of both CGRPand galanin-immunoreactive sprouts, vs. the lesioned control animals kept on the normal diet (+ 140% and + 90%, respectively, both p < 0.05). A signifi cant increase was also seen in integrin immunoreactivity, with an increase of 20% for the αM-, and 167% for the β1-integrin subunit, respectively (both p < 0.05) in animals receiving the DHA-supplemented diet, in comparison with animals on the control diet. The intake of DHA after injury also led to a better functional outcome, although the increase in whisker mobility 14 days after injury (+ 67% vs. controls) was not statistically signifi cant. These results show that the dietary supplementation with DHA in the period following facial nerve injury has signifi cant effects on the response of both neurons and microglia to injury, and appears to promote a pro-regenerative response. This suggests that DHA could have a neuroprotective potential in the treatment of peripheral nerve injury.