Combined neurosurgical and orbital intervention for spheno-orbital meningiomas - the Manchester experience.

PURPOSE: Surgical resection of spheno-orbital meningioma (SOM) is challenging, requiring a multidisciplinary surgical approach. We present our experience of the surgical management of patients with SOM. METHODS: A retrospective analysis of patients with SOM who underwent joint neurosurgical and orbital surgical procedures between January 2000 and June 2017. Pre-operative clinical signs, indication for surgery, surgical complications and post-operative outcomes were recorded. RESULTS: Twenty-four operations were performed. Mean age was 49.5 years. Ninety-two percent of patients were female. Pre-operatively mean Snellen acuity vision was 6/12; 13 (54%) had an RAPD; 12 (50%) had reduced colour vision; 16 (67%) had a visual field defect. The majority (21 patients, 88%) had proptosis (average 4.5 mm ± 2.8 mm). The indication for surgery was evidence of visual dysfunction in 17 (71%), the remaining 7 (29%) had high risk of visual loss clinically or radiologically. Three-months post operatively, vision was stable in 13 (58%), improved in 6 (21%) and worse in 5 (17%). Average long-term follow-up was 82 months (1-220). Fourteen (58%) maintain improved or stable visual function. Four (17%) had reduced vision due to regrowth of the tumour at an average of 24 months. CONCLUSION: SOMs are very challenging to treat surgically. In this cohort the patients were predominantly young females with aggressive disease. Visual function was improved or stabilised in 79% of the patients.

Spinal ependymomas in NF2: a surgical disease?

The management of spinal cord ependymomas in Neurofibromatosis Type 2 (NF2) has traditionally been conservative, in contrast to the management of sporadic cases; the assumption being that, in the context of NF2, they did not cause morbidity. With modern management and improved outcome of other NF2 tumours, this assumption, and therefore the lack of role for surgery, has been questioned. To compare the outcome of conservative treatment of spinal ependymomas in NF2 with surgical intervention in selected patients. Retrospective review at two NF2 centers, Manchester, UK and Paris/Lille, France. In Manchester patients were managed conservatively. In France surgery was a treatment option. Inclusion in the study was based on tumor length of greater than 1.5 cm. The primary parameter assessed was acquired neurological deficit measured by the Modified McCormick Outcome Score. 24 patients from Manchester and 46 patients from France were analyzed. From Manchester, 27% of these patients deteriorated during the course of follow-up. This effectively represents the natural history of ependymomas in NF2. Of the surgical cases, 23% deteriorated postoperatively, but only 2/18 (11%) of those operated on in the NF2 specialist centers. Comparison of the two specialist centers Manchester/France showed a significantly improved outcome (P = 0.012, χ2 test) in the actively surgical center. Spinal ependymomas produce morbidity. Surgery can prevent or improve this in selected cases but can itself can produce morbidity. Surgery should be considered in growing/symptomatic ependymomas, particularly in the absence of overwhelming tumor load where bevacizumab is the preferred option.

Modified RS-LAMP assay and use of lateral flow devices for rapid detection of Leifsonia xyli subsp. xyli.

Ratoon stunt (RS) caused by bacterium Leifsonia xyli subsp. xyli (Lxx) results in substantial yield losses in sugarcane (Saccharum sp. L. hybrid). Since RS does not produce reliable symptoms in the field, laboratory-based techniques are necessary for detection. Loop-mediated isothermal amplification (LAMP) assay overcomes the limitations of laboratory-based techniques which are costly, time consuming and cannot be used for near-field detection. A sensitive LAMP assay was developed to detect Lxx at 65°C in 30 min. However, carry-over contamination affected the reliability of the assay. In the present study, contaminants were successfully eliminated by incorporation of uracil nucleoside glycosylase (1 U µl-1 ) into the LAMP assay and incubation for 10 min at 37°C. To avoid the use of colorimetric reagents, lateral flow devices were successfully used for the detection of LAMP products and were equally sensitive to detection by agarose gel electrophoresis. The use of exudate from leaf sheath discs as an alternate template for the LAMP assay was found to be less sensitive than xylem sap. The preprepared master mix could be stored for up to 4 months at -20°C without any reduction in performance. These changes make the assay suitable for near-field detection in laboratories with basic facilities. SIGNIFICANCE AND IMPACT OF THE STUDY: This study presents a modified loop-mediated isothermal amplification (LAMP) assay for the detection of Leifsonia xyli subsp. xyli. Modifications include incorporation of uracil nucleoside glycosylase to eliminate carry-over contamination and substitution of colorimetric detection for the use of lateral flow devices. LAMP master mix was preprepared and was stably stored up to 4 months at -20°C. Sugarcane leaf sheaths worked well as a substitute to xylem sap as template, although the sensitivity was lower. These modifications allow the assay to be conducted without contamination concerns and reduction in set up time, making it ideal for near-field diagnosis.

Hearing optimisation in neurofibromatosis type 2: A systematic review.

BACKGROUND: It is common for patients with neurofibromatosis type 2 to develop bilateral profound hearing loss hearing loss, and this is one of the main determinants of quality of life in this patient group. OBJECTIVES: The aim of this systematic review was to review the current literature regarding hearing outcomes of treatments for vestibular schwannomas in neurofibromatosis type 2 including conservative and medical management, radiotherapy, hearing preservation surgery and auditory implantation in order to determine the most effective way of preserving or rehabilitating hearing. SEARCH STRATEGY: A MESH search in PubMed using search terms (('Neurofibromatosis 2' [Mesh]) AND 'Neuroma, Acoustic'[Mesh]) AND 'Hearing Loss' [Mesh] was performed. A search using keywords was also performed. Studies with adequate hearing outcome data were included. With the exception of the cochlear implant studies (cohort size was very small), case studies were excluded. EVALUATION METHOD: The GRADE system was used to assess quality of publication. Formal statistical analysis of data was not performed because of very heterogenous data reporting. RESULTS: Conservative management offers the best chance of hearing preservation in stable tumours. The use of bevacizumab probably improves the likelihood of hearing preservation in growing tumours in the short term and is probably more effective than hearing preservation surgery and radiotherapy in preserving hearing. Of the hearing preservation interventions, hearing preservation surgery probably offers better hearing preservation rates than radiotherapy for small tumours but recurrence rates for hearing preservation surgery were high. For patients with profound hearing loss, cochlear implantation provides significantly better auditory outcomes than auditory brainstem implantation. Patients with untreated stable tumours are likely to achieve the best outcomes from cochlear implantation. Those who have had their tumours treated with surgery or radiotherapy do not gain as much benefit from cochlear implantation than those with untreated tumours. CONCLUSIONS: This review summarises the current literature related to hearing preservation/rehabilitation in patients with NF2. Whilst it provides indicative data, the quality of the data was low and should be interpreted with care. It is also important to consider that the management of vestibular schwannomas in NF2 is complex and decision-making is determined by many factors, not just the need to preserve hearing.

Source and risk factors of a cutaneous anthrax outbreak, Jiangsu, Eastern China, 2012.

Anthrax is still a severe public health problem and threat to human health. A cutaneous anthrax outbreak occurred in Jiangsu Province, a non-endemic anthrax region of eastern China, from July to August 2012. Epidemiological and laboratory investigation were initiated to trace the source of infection and identify the risk factors of the outbreak. On 25 July 2012, 17 persons were exposed to a sick cow, which had been imported from northeast China a few days previously. Of the 17 exposed, eight developed symptoms between 1 and 8 days and were diagnosed as cutaneous anthrax cases. Three main genes of Bacillus anthracis were detected from both human and cow meat samples, indicating that the outbreak was associated with this infected cow. A retrospective cohort study showed that contact with blood and presence of skin damage contributed to the case infection with B. anthracis. The outbreak highlights the need to enhance quarantine for imported livestock, which should have been vaccinated prior to importation, the significance of education for high-risk individuals, and training for primary healthcare workers even in anthrax-free areas.

Bilateral vestibular schwannomas in older patients: NF2 or chance?

BACKGROUND: Neurofibromatosis type 2 (NF2) is an autosomal dominant condition with high spontaneous mutation rate which predisposes to the development of multiple nerve sheath tumours (schwannomas), meningiomas and ependymoma. The cardinal feature and main diagnostic criterion for the diagnosis of NF2 remains the development of bilateral vestibular schwannoma (BVS). With increasing use of MRI screening the possibility of a 'chance' diagnosis of BVS has been mooted with a potential frequency of one in two million people in their lifetime. Until now, however, no evidence for such an event has been published. We aimed to demonstrate that chance occurrence can occur and to estimate its frequency among those with just BVS late in life. METHODS: Two vestibular schwannomas from the same patient were DNA sequenced and underwent loss of heterozygosity analysis. RESULTS: We show that a man who developed BVS, at ages 52 and 67 years developed these tumours sporadically by demonstrating that there were no molecular events in common between the two tumours. Furthermore from a database of over 1200 patients with NF2, we have estimated that ~25% of cases of BVS over 50 years and 50% over 70 years of age where no other features of NF2 are present represent a chance occurrence rather than due to an underlying mosaic or constitutional NF2 mutation. CONCLUSIONS: Patients presenting with BVS later in life should be appraised of the potential likelihood they may not have NF2 and the resultant further reduction in risks of transmission to offspring.

Temporal and spatial patterns of diarrhoea in the Mekong Delta area, Vietnam.

This study examined the temporal and spatial patterns of diarrhoea in relation to hydro-meteorological factors in the Mekong Delta area in Vietnam. A time-series design was applied to examine the temporal pattern of the climate-diarrhoea relationship using Poisson regression models. Spatial analysis was applied to examine the spatial clusters of diarrhoea using Global Moran's I and local indicators of spatial autocorrelation (LISA). The temporal pattern showed that the highest peak of diarrhoea was from weeks 30-42 corresponding to August-October annually. A 1 cm increase in river water level at a lag of 1 week was associated with a small [0·07%, 95% confidence interval (CI) 0·01-0·1] increase in the diarrhoeal rate. A 1 °C increase in temperature at lag of 2 and 4 weeks was associated with a 1·5% (95% CI 0·3-2·7) and 1·1% (95% CI 0·1-2·3) increase in diarrhoeal risk, respectively. Relative humidity and diarrhoeal risk were in nonlinear relationship. The spatial analysis showed significant clustering of diarrhoea, and the LISA map shows three multi-centred diarrhoeal clusters and three single-centred clusters in the research location. The findings suggest that climatic conditions projected to be associated with climate change have important implication for human health impact in the Mekong Delta region.

A neuroimaging measure to capture heterogeneous patterns of atrophy in Parkinson's disease and dementia with Lewy bodies.

INTRODUCTION: Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) show heterogeneous brain atrophy patterns which group-average analyses fail to capture. Neuroanatomical normative modelling overcomes this by comparing individuals to a large reference cohort. Patient-specific atrophy patterns are measured objectively and summarised to index overall neurodegeneration (the 'total outlier count'). We aimed to quantify patterns of neurodegenerative dissimilarity in participants with PD and DLB and evaluate the potential clinical relevance of total outlier count by testing its association with key clinical measures in PD and DLB. MATERIALS AND METHODS: We included 108 participants with PD and 61 with DLB. PD participants were subclassified into high and low visual performers as this has previously been shown to stratify those at increased dementia risk. We generated z-scores from T1w-MRI scans for each participant relative to normative regional cortical thickness and subcortical volumes, modelled in a reference cohort (n = 58,836). Outliers (z < -1.96) were aggregated across 169 brain regions per participant. To measure dissimilarity, individuals' Hamming distance scores were calculated. We also examined total outlier counts between high versus low visual performance in PD; and PD versus DLB; and tested associations between these and cognition. RESULTS: There was significantly greater inter-individual dissimilarity in brain-outlier patterns in PD poor compared to high visual performers (W = 522.5; p < 0.01) and in DLB compared to PD (W = 5649; p < 0.01). PD poor visual performers had significantly greater total outlier counts compared to high (ß = -4.73 (SE = 1.30); t = -3.64; p < 0.01) whereas a conventional group-level GLM failed to identify differences. Higher total outlier counts were associated with poorer MoCA (ß = -0.55 (SE = 0.27), t = -2.04, p = 0.05) and composite cognitive scores (ß = -2.01 (SE = 0.79); t = -2.54; p = 0.02) in DLB, and visuoperception (ß = -0.67 (SE = 0.19); t = -3.59; p < 0.01), in PD. CONCLUSIONS: Neuroanatomical normative modelling shows promise as a clinically informative technique in PD and DLB, where patterns of atrophy are variable.

Outcome of translabyrinthine surgery for vestibular schwannoma in neurofibromatosis type 2.

OBJECTIVES: To analyse the long-term outcome of translabyrinthine surgery for vestibular schwannoma (VS) in neurofibromatosis type 2 (NF2). RESEARCH TYPE: Retrospective cohort study. SETTING: Two tertiary referral NF2 units. PATIENTS: One hundred and forty eight translabyrinthine operations for patients with VS were performed. Preoperative stereotactic radiotherapy had been performed on 12(9.4%) patients. RESULTS: Mean tumour size was 3.1 cm. Total tumour excision was achieved in 66% of cases, capsular remnants were left in 24% of cases, and subtotal excision was achieved in 5% and partial removal was achieved in 5%. The radiological residual/recurrence rate was 13.9%. The perioperative mortality was 1.6%. At 2 years postoperatively, facial function was expressed in terms of House-Brackmann score (HB): HB 1 in 53.4%, HB 1/2 in 61.3%, HB 1-3 in 83.2% and HB 4-6 in 16.8%. All nine patients who underwent surgery following failed stereotactic radiotherapy had HB 3 function or better. Among 9.5% of the cases, 14 facial nerves were lost during surgery and repaired using direct anastomosis or grafting. There was no tinnitus present preoperatively in 27% of the cases, and 22% of patients developed tinnitus postoperatively. In patients with preoperative tinnitus, 61% remained the same, 17% got it resolved and only in 21% it worsened. The preoperative hydrocephalus rate was 26%, and among 15% of the cases five ventriculo-peritoneal (VP) shunts were performed. The cerebrospinal fluid leak rate was 2.5%. Fifty-six patients underwent auditory brainstem implantation (ABI) and two patients had cochlear implant (CI) sleepers inserted. CONCLUSIONS: The management of patients with NF2 presents the clinician with a formidable challenge with many patients still presenting themselves late with the neurological compromise and a large tumour load. There is still an argument for the management by observation until the neurological compromise dictates interventional treatment particularly with the option of hearing rehabilitation with ABI or CI. The translabyrinthine approach provides a very satisfactory means of reducing the overall tumour volume.

A challenging case of sporadic melanocytoma of the jugular foramen.

BACKGROUND: The jugular foramen (JF) can be the site of several tumours. Paragangliomas, schwannomas and meningiomas are the most commonly reported. We describe a case of melanocytoma originating from the JF and presenting with an accessory nerve palsy. ILLUSTRATIVE CASE: A 48-year-old woman presented with a 6-month history of cervical and left shoulder pain with wasting and weakness of the left trapezius. A Magnetic Resonance Imaging (MRI) showed a T1-hyperintense, T2-isointense, heterogeneously enhancing lesion involving the left JF and extending into the cerebello-medullary and cerebello-pontine cisterns. A retrosigmoid craniotomy was performed and a near-total removal achieved. The accessory nerve was involved by tumour and could not be preserved. Given the diagnostic uncertainty between melanotic schwannoma, metastatic melanoma and meningeal melanocytoma, next generation sequencing and genome-wide DNA methylation arrays were performed, documenting a mutation in GNA11 (c.6226A>T, p. Gln209Leu) and a methylation profile consistent with melanocytoma. The patient underwent adjuvant fractionated radiotherapy of the tumour remnant. A follow-up MRI 4 years after surgery did not show any tumour recurrence. CONCLUSIONS: The differential diagnosis of skull base pigmented tumours can be challenging, particularly when they occur in unusual locations such as the JF. They can be misdiagnosed given their similar clinical, neuroradiological and pathological features if anatomy of the site of origin is not carefully considered and molecular tests are not performed, leading to erroneous treatment and follow-up planning.

Cyclophilins: a new family of proteins involved in intracellular folding.

Proteins of the cyclophilin family display two intriguing properties. On the one hand, they are the intracellular receptors for the immunosuppressive drug cyclosporin A (CsA); on the other hand, they function in vitro as enzymes that catalyse slow steps in protein folding. A dissection of the role of CsA in mediating immunosuppression, together with recent studies on the biology of cyclophilins in the absence of this ligand, is providing fundamental insight into the cellular function of this protein family.

Determinants of variation in human serum paraoxonase activity.

Paraoxonase-1 (PON1) is associated with high-density lipoprotein (HDL) particles and is believed to contribute to antiatherogenic properties of HDLs. We assessed the determinants of PON1 activity variation using different substrates of the enzyme. PON1 activity in serum samples from 922 participants in the San Antonio Family Heart Study was assayed using a reliable microplate format with three substrates: paraoxon, phenyl acetate and the lactone dihydrocoumarin. There were major differences among results from the three substrates in degree of effect by various environmental and genetic factors, suggesting that knowledge of one substrate activity alone may not provide a complete sense of PON1 metabolism. Three significant demographic covariates (age, smoking status and contraceptive usage) together explained 1-6% of phenotypic variance, whereas four metabolic covariates representing lipoprotein metabolism (apoAII, apoAI, triglycerides and non-HDL cholesterol) explained 4-19%. Genes explained 65-92% of phenotypic variance and the dominant genetic effect was exerted by a locus mapping at or near the protein structural locus (PON1) on chromosome 7. Additional genes influencing PON1 activity were localized to chromosomes 3 and 14. Our study identified environmental and genetic determinants of PON1 activity that accounted for 88-97% of total phenotypic variance, suggesting that few, if any, major biological determinants are unrepresented in the models.

Enterogenous cysts of the cerebellopontine angle: short review illustrated by two new patients.

Intracranial enterogenous cysts are an uncommon entity rarely found in the midline within the posterior cranial fossa. The occurrence of an enterogenous cyst in the cerebellopontine angle is exceptional. We present two new cases of cerebellopontine angle (CPA) enterogenous cysts and review the literature to clarify the diagnosis and the management of these lesions. Eighteen cases of CPA intradural enterogenous cysts have been reported to date, including the two cases presented in this article. All of them were symptomatic and underwent surgical treatment. After surgery, the symptomatic recurrence occurred in 31% of the patients, most of which had partial excision. Considering our patients and the published cases in the literature we suggest that the aim of surgery should be total removal of cyst and its content whenever possible. When partial resection of the cyst is performed, we recommend long-term clinical and neuroradiological follow-up.

Trigeminal schwannomas.

Trigeminal schwannomas are the second most common intracranial schwannoma. They may occur sporadically or in association with neurofibromatosis type 2. The vast majority are benign in nature although malignancies have been reported. They may present with a range of symptoms because of their variable locations in areas with multiple differing functional activities. There is little understanding of the natural history of these tumours, and the choice of treatment includes surgery, stereotactic radiosurgery and fractionated radiotherapy. This article reviews the management options and outcomes. The incidence of recurrence and the time interval following treatment to recurrence is unpredictable.

Water sorption in silicone foam containing diatomaceous earth.

Room temperature vulcanizing (RTV) silicone foams are commonly used for compression sealing, structural support, packaging, and damping applications. The presence of sorbed water in foams can affect the mechanical and chemical properties of these materials. In order to investigate water sorption behavior, a silicone foam containing diatomaceous earth filler was synthesized and studied for water uptake characteristics at 20, 50, and 80 degrees C. Type II equilibrium and bimodal kinetic behavior that was governed by a rapid initial uptake followed by a prolonged sorption over a larger time scale was observed. In order to explain this bimodal behavior, the major components of this foam-the silicone polymer and the diatomaceous earth-were independently studied for their water equilibrium behavior and uptake kinetic characteristics. Type II equilibrium was observed for both components. The kinetic behavior of the silicone polymer was governed by a very rapid uptake of water. The kinetic behavior of the diatomaceous earth was governed by a rapid initial uptake followed by a prolonged sorption over a larger time scale. A physically based and thermodynamically consistent mathematical model describing the water equilibrium and kinetics in diatomaceous earth and silicone polymer components, was employed to characterize the data. This model formed the basis of a predictive model for estimation of water sorption in filled silicone foam. The predictive model was tested against sorption and desorption data yielding favorable results for a range of temperatures.

Ran alters nuclear pore complex conformation.

Transport across the nuclear membranes occurs through the nuclear pore complex (NPC), and is mediated by soluble transport factors including Ran, a small GTPase that is generally GDP-bound during import and GTP-bound for export. The dynamic nature of the NPC structure suggests a possible active role for it in driving translocation. Here we show that RanGTP but not RanGDP causes alterations of NPC structure when injected into the cytoplasm of Xenopus oocytes, including compaction of the NPC and extension of the cytoplasmic filaments. RanGTP caused accumulation of nucleoplasmin-gold along the length of extended cytoplasmic filaments, whereas RanGDP caused accumulation around the cytoplasmic rim of the NPC. This suggests a possible role for Ran in altering the conformation of the cytoplasmic filaments during transport.

The effect of sequence homozygosity on the frequency of X-chromosomal exchange in Drosophila melanogaster females.

The repair of mismatched heteroduplex DNA has been implicated in the normal resolution of meiotic exchange events. Although sequence microheterogeneity over defined intervals of homologous chromosomes has been correlated with local effects on recombination, this correlation has not previously been extended to effects on chromosomal levels of exchange. In order to determine the role of microheterogeneity in normal exchange between homologs, a system was devised for monitoring exchange between isogenic X chromosomes. Lack of microheterogeneity did not significantly alter the frequency of exchange along the isogenic X chromosomes relative to controls or to previously reported values. There were, however, characteristic levels of exchange intrinsic to the cloned X chromosomes in each of the lines tested.

arc6, A Fertile Arabidopsis Mutant with Only Two Mesophyll Cell Chloroplasts.

A novel mutant of Arabidopsis thaliana, arc6 (accumulation and replication of chloroplasts), has been isolated from a transfer DNA-mutagenized population of Arabidopsis seedlings. arc6 has the most extreme arc mutant phenotype we have yet described, with only one to three chloroplasts per leaf mesophyll cell compared to a mean of 83 in cells of the wild-type var Wassilewskija. The chloroplasts of arc6 are 20-fold larger than wild-type chloroplasts.Chloroplast division is almost certainly precluded in arc6 mesophyll cells, since chloroplast number per cell does not increase during mesophyll cell expansion. arc6 chloroplasts are long and thin in cross-section and only one-half the width of wild-type chloroplasts and the arrangement of thylakoid membranes is largely unaltered. arc6 segregates as a monogenic recessive nuclear mutation in a normal Mendelian manner and the arc6 phenotype is stably inherited for at least four generations. arc6 plants grow normally and are fertile, although the rosette leaves appear curled and twisted. arc6 plants accumulate 70 to 75% of the biomass of wild type. The phenotype of this novel mutant is discussed in relation to the nature of the control of chloroplast division in leaf cells.