Mr Thomas Santarius

Neurosurgeon, Consultant Neurosurgeon, Cambridge University Hospitals NHS Trust
  • Cambridge, United Kingdom
  • English
  • Best at: Meningioma, glioma, cavernoma, metastasis, pituitary & pineal, craniopharyngioma, ependymoma

Mr Thomas Santarius specialises in brain tumour surgery, both in adults and in children. There are over 140 types of brain tumours and Mr Santarius has particular expertise in treating the following brain tumours: metastases to the brain, meningiomas, low-grade (LGGs) and high-grade (HGGs) gliomas, pituitary adenomas, craniopharyngiomas, ependymomas and other intraventricular tumour, pilocytic astrocytomas, pineal region tumours, brainstem tumours and cavernomas. Mr Santarius has completed his neurosurgical training in Cambridge gaining additional sub-specialist experience in other neurosurgery centres, including the Great Ormond Street Hospital for Sick Children in London; the Brigham and Women’s and Children’s Hospital in Boston, USA; Gui de Chauliac Hospital in Montpellier, France; and UCSF Medical Center, San Francisco, USA. His clinical and teaching efforts are focused on perfecting surgical techniques, while his research aims to better understand the biology of brain tumours.

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Statistics.

Achievements of Mr Thomas Santarius

Trustedoctor credentials
-
Clinical endorsements
85
Articles
266
Scientific
co-authors
Trustedoctor credentials
5
General Speciality
25
Subspeciality
1
Languages

About.

Information about Mr Thomas Santarius

Timeline
Place
Country
Position
Focus
2010
-
United Kingdom
FRCS(SN)
Surgical Neurology
Timeline
Place
Country
Position
Focus
-
-
-
-
-

Clinical experience.

General speciality (5)
Patients per year
Patients total
general brain tumor surgery
>100
-
glioma surgery
>10
-
skull base surgery
>10
0
pediatric neurosurgery
>50
0
pediatric neurosurgery
>50
-
Tumor speciality (25)
Patients per year
Patients total
cavernoma
>10
-
pituitary adenoma
>10
-
meningioma
>10
-
pineal tumors
>10
-
craniopharyngeoma
>10
-
anaplastic astrocytoma
>10
0
plexus papilloma
>10
0
ependymoma
>10
0
epidermoid
>10
0
ganglioglioma
>10
0
medulloblastoma
>10
0
brainstem glioma
>10
0
dermoid
>10
0
at/rt
>10
0
oligodendroglioma
>10
0
pilocytic astrocytoma
>10
0
rathke cyst
>10
0
glioblastoma
>10
0
metastasis
>50
0
pnet
>10
0
sega
>10
0
subependymoma
>10
0
schwannoma
>10
0
gliosarkoma
>10
0
low grade astrocytoma
>10
0
Techniques (6)
Patients per year
Patients total
fluorescence guided surgery
>50
0
intra-operative mapping and monitoring
>10
0
keyhole approach
>50
0
minimal invasive surgery
>50
0
neuronavigation
>50
0
endoscopic surgery
>50
0

Skills & Endorsements.

General speciality
glioma surgery
general brain tumor surgery
pediatric neurosurgery
skull base surgery
Tumor speciality
pineal tumors
pituitary adenoma
craniopharyngeoma
meningioma
cavernoma
anaplastic astrocytoma
anaplastic oligodendroglioma
astrocytoma
at/rt
brainstem glioma
dermoid
ependymoma
epidermoid
ganglioglioma
glioblastoma
gliosarkoma
low grade astrocytoma
medulloblastoma
lymphoma
metastasis
neuroblastoma
oligodendroglioma
pilocytic astrocytoma
plexus papilloma
pnet
rathke cyst
schwannoma
sega
subependymoma
Techniques
endoscopic surgery
fluorescence guided surgery
intra-operative mapping and monitoring
minimal invasive surgery
neuronavigation

Academic research.

85
Total articles
  • surgery - 25
14
brain cancer articles - Impact Factor
  • surgery - 4
Stereoscopic Three-Dimensional Neuroanatomy Lectures Enhance Neurosurgical Training: Prospective Comparison with Traditional Teaching.

Stereoscopic three-dimensional (3D) imaging is increasingly used in the teaching of neuroanatomy and although this is mainly aimed at undergraduate medical students, it has enormous potential for enhancing the training of neurosurgeons. This study aims to assess whether 3D lecturing is an effective method of enhancing the knowledge and confidence of neurosurgeons and how it compares with traditional two-dimensional (2D) lecturing and cadaveric training.

Methodological shortcomings in the literature evaluating the role and applications of 3D training for surgical trainees.

There has been an increased interest in the use of three-dimensional (3D) technology in surgical training. We wish to appraise the methodological rigor applied to evaluating the role and applications of 3D technology in surgical training, in particular, on the validity of these models and assessment methods in simulated surgical training.

Correlation of volumetric growth and histological grade in 50 meningiomas.

Advances in radiological imaging techniques have enabled volumetric measurements of meningiomas to be easily monitored using serial imaging scans. There is limited literature on the relationship between tumour growth rates and the WHO classification of meningiomas despite tumour growth being a major determinant of type and timing of intervention. Volumetric growth has been successfully used to assess growth of low-grade glioma; however, there is limited information on the volumetric growth rate (VGR) of meningiomas. This study aimed to determine the reliability of VGR measurement in patients with meningioma, assess the relationship between VGR and 2016 WHO grading as well as clinical applicability of VGR in monitoring meningioma growth.

Survey on current cognitive practices within the European Low-Grade Glioma Network: towards a European assessment protocol.

The European Low-Grade Glioma network indicated a need to better understand common practices regarding the managing of diffuse low-grade gliomas. This area has experienced great advances in recent years.

Concomitant Primary CNS Lymphoma and FSH-Pituitary Adenoma Arising Within the Sella. Entirely Coincidental?

Collision tumors are the simultaneous occurrence of more than one type of neoplasm within an anatomic space. In the pituitary sella, collision tumors are exceedingly rare, and not much is known about their etiology and prognosis.

Improved long-term survival with subdural drains following evacuation of chronic subdural haematoma.

Chronic subdural haematoma (CSDH) is a common condition that is effectively managed by burrhole drainage but requires repeat surgery in a significant minority of patients. The Cambridge Chronic Subdural Haematoma Trial (CCSHT) was a randomised controlled study that showed placement of subdural drains for 48 h following burrhole evacuation significantly reduces the incidence of reoperation and improves survival at 6 months. The present study examined the long-term survival of the patients in the trial.

The Effect of 3-Dimensional Simulation on Neurosurgical Skill Acquisition and Surgical Performance: A Review of the Literature.

In recent years, 3-dimensional (3D) simulation of neurosurgical procedures has become increasingly popular as an addition to training programmes. However, there remains little objective evidence of its effectiveness in improving live surgical skill. This review analysed the current literature in 3D neurosurgical simulation, highlighting remaining gaps in the evidence base for improvement in surgical performance and suggests useful future research directions.

Clinical Experience and Results of Microsurgical Resection of Arterioveonous Malformation in the Presence of Space-Occupying Intracerebral Hematoma.

Management of ruptured arteriovenous malformations (AVMs) with a mass-producing intracerebral hematoma (ICH) represents a surgical dilemma.

Volumetric growth rates of meningioma and its correlation with histological diagnosis and clinical outcome: a systematic review.

Tumour growth has been used to successfully predict progression-free survival in low-grade glioma. This systematic review sought to establish the evidence base regarding the correlation of volumetric growth rates with histological diagnosis and potential to predict clinical outcome in patients with meningioma.

Reporting of patient-reported health-related quality of life in adults with diffuse low-grade glioma: a systematic review.

Patient-reported health-related quality of life (HRQoL) analysis can provide important information for managing the balance between treatment benefits and treatment-related adverse effects on quality of life (QoL). This systematic review sought to identify the range of HRQoL measures used for patients with diffuse hemispheric WHO grade II glioma (DLGG) and assess the quality of HRQoL reporting.

Core Outcomes and Common Data Elements in Chronic Subdural Hematoma: A Systematic Review of the Literature Focusing on Baseline and Peri-Operative Care Data Elements.

Chronic subdural hematoma (CSDH) is an increasingly common subtype of head injury, especially in the elderly population. The optimization of treatment strategies has been hampered by the collection of heterogeneous outcome measures and data elements, precluding cross-study comparisons. This study aimed to quantify the heterogeneity of data elements in the pre-operative, operative, and post-operative phases of care, and build the basis for the development of a set of common data elements (CDEs) for CSDH. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered with the PROSPERO register of systematic reviews (CRD42014007266). All full-text English studies with more than 10 patients (prospective) or more than 100 patients (retrospective) published after 1990 examining clinical outcomes in CSDH were eligible for inclusion. One hundred two eligible studies were found. Only 40 studies (39.2%) reported the main presenting symptom/feature and 24 (23.5%) reported additional symptoms/features. Admitting neurological/functional status was classified by the Glasgow Coma Scale (25 studies; 24.5%), the Markwalder Score (26 studies; 25.5%) and the modified Rankin Scale (three studies; 2.9%). Fifty-four studies (52.9%) made some mention of patient comorbidities and 58 studies (56.9%) reported the proportion or excluded patients on anticoagulant medication. Eighteen studies (17.6%) reported baseline coagulation status. Sixty-four studies (62.7%) stratified or assessed severity based on radiological findings, although the methods used varied widely. There was variable reporting of surgical technique and post-operative care; 32 studies (31.4%) made no mention of whether the operations were performed under general or local anesthetic. This study, a part of the Core Outcomes and Common Data Elements in CSDH (CODE-CSDH) project, confirms and quantifies the heterogeneity of data elements collected and reported in CSDH studies to date. It establishes the basis for the consensus-based development of a set of common data elements, facilitating robust cross-study comparisons and resulting improvements in patient outcomes.

Germinoma of the medulla oblongata - A case report.

We describe a case of primary intracranial medulla oblongata germinoma in a 23-year-old female who presented with deteriorating balance and mobility. Imaging demonstrated an exophytic lesion arising from the dorsal medulla oblongata and extending into the fourth ventricle. The tissue sample was obtained via suboccipital craniotomy and a diagnosis of a primary medullary germinoma was made. The patient underwent whole craniospinal axis radiotherapy and remains well and recurrence-free at 1-year follow up.

Core Outcomes and Common Data Elements in Chronic Subdural Hematoma: A Systematic Review of the Literature Focusing on Reported Outcomes.

The plethora of studies in chronic subdural hematoma (CSDH) has not resulted in the development of an evidence-based treatment strategy, largely due to heterogeneous outcome measures that preclude cross-study comparisons and guideline development. This study aimed to identify and quantify the heterogeneity of outcome measures reported in the CSDH literature and to build a case for the development of a consensus-based core outcome set. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered with the PROSPERO international prospective register of systematic reviews (CRD42014007266). All full-text English language studies with >10 patients (prospective) or >100 patients (retrospective) published after 1990 examining clinical outcomes in CSDH were eligible for inclusion. One hundred two eligible studies were found. There were 14 (13.7%) randomized controlled trials, one single arm trial (1.0%), 25 (24.5%) cohort comparison studies, and 62 (60.8%) prospective or retrospective cohort studies. Outcome domains reported by the studies included mortality (63.8% of included studies), recurrence (94.1%), complications (48.0%), functional outcomes (40.2%), and radiological (38.2%) outcomes. There was significant heterogeneity in the definitions of the outcome measures, as evidenced by the seven different definitions of the term "recurrence," with no definition given in 19 studies. The time-points of assessment for all the outcome domains varied greatly from inpatient/hospital discharge to 18 months. This study establishes and quantifies the heterogeneity of outcome measure reporting in CSDH and builds the case for the development of a robust consensus-based core outcome set for future studies to adhere to as part of the Core Outcomes and Common Data Elements in CSDH (CODE-CSDH) project.

Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer.

Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C > T and A > G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. A number of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria and is fundamentally linked to mtDNA replication.

Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey.

Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children.

Chronic subdural haematoma: modern management and emerging therapies.

Chronic subdural haematoma (CSDH) is one of the most common neurological disorders, and is especially prevalent among elderly individuals. Surgical evacuation is the mainstay of management for symptomatic patients or haematomas exerting significant mass effect. Although burr hole craniostomy is the most widely practised technique worldwide, approximately 10-20% of surgically treated patients experience postoperative recurrence necessitating reoperation. Given the increasing incidence of CSDH in a growing elderly population, a need exists for refined techniques that combine a minimally invasive approach with clinical efficacy and cost-effectiveness. In addition, nonsurgical treatment modalities, such as steroids, are attracting considerable interest, as they have the potential to reduce postoperative recurrence or even replace the need for surgery in selected patients. This Review provides an overview of the contemporary management of CSDH and presents considerations regarding future approaches that could further optimize patient care and outcomes.

Alternative cost-effective method to record 3D intra-operative images: a technical note.

The educational value of stereoscopic imaging in neurosurgical training has increasingly been appreciated and its use increased during the last decade. We describe a technique that we developed to acquire and reproduce intra-operative stereoscopic images.

Current concepts in the surgical management of glioma patients.

The scientific basis for the surgical management of patients with glioma is rapidly evolving. The infiltrative nature of these cancers precludes a surgical cure, but despite this, cytoreductive surgery remains central to high-quality patient care. In addition to tissue sampling for accurate histopathological diagnosis and molecular genetic characterisation, clinical benefit from decompression of space-occupying lesions and microsurgical cytoreduction has been reported in patients with different grades of glioma. By integrating advanced surgical techniques with molecular genetic characterisation of the disease and targeted radiotherapy and chemotherapy, it is possible to construct a programme of personalised surgical therapy throughout the patient journey. The goal of therapeutic packages tailored to each patient is to optimise patient safety and clinical outcome and must be delivered in a multidisciplinary setting. Here we review the current concepts that underlie surgical subspecialisation in the management of patients with glioma.

Twist-drill craniostomy with hollow screws for evacuation of chronic subdural hematoma.

OBJECT.: The incidence of chronic subdural hematoma (CSDH) is expected to increase substantially over the next 25 years. Continuing refinement of techniques for surgical evacuation is essential for optimizing patient outcomes. A novel technique involving a hollow screw, which is threaded through a twist-drill hole in the cranium and then connected to a closed drainage system, has been increasing in popularity. The aim of this systematic review is to collate and analyze the published experience with this novel technique and to evaluate its efficacy in comparison with the other surgical treatment methods.

Causes of neurological deficits following clipping of 200 consecutive ruptured aneurysms in patients with good-grade aneurysmal subarachnoid haemorrhage.

The surgical risk of unruptured aneurysms is well quantified. Although the outcomes for ruptured aneurysms are also well described, due to the concurrent morbidity from the natural history of the haemorrhage, the relative contributions of surgery and natural history to outcome following aneurysmal subarachnoid haemorrhage (SAH) is not. Our aim was to quantify these risks.

Processed pseudogenes acquired somatically during cancer development.

Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5' truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context.

Delayed neurological deficit following resection of tuberculum sellae meningioma: report of two cases, one with permanent and one with reversible visual impairment.

The most common presentation of patients with tuberculum sellae meningiomas is visual loss, and surgical resection is the main mode of treatment. Preservation of vision is not only the main objective of the surgery; loss of vision is also its main risk. Visual deterioration following surgery is usually apparent immediately post-operatively. Here we present two cases of patients who underwent resection of tuberculum sellae meningioma and whose vision following surgery was initially unchanged until the postoperative day two when dramatic visual deterioration occurred. In the first case this resulted in blindness, whereas in the second case vision recovered back to the preoperative state. The possible mechanisms of visual deterioration and modes of treatment are discussed.

Giant intracranial hemangioma in a neonate.

In this report we detail the case of an infant presenting with a giant intracranial congenital hemangioma and describe the clinical features and surgical management. Congenital hemangiomas are benign vascular tumors that typically present as skin lesions in neonates and infants. On rare occasions they present as intracranial tumors. The possibility that these tumors may undergo spontaneous regression poses a treatment dilemma.

Diffuse cerebral vasospasm following resection of a hypoglossal schwannoma in a child.

Diffuse cerebral vasospasm is a rare complication following tumour resection. This phenomenon seems to be even rarer in the paediatric population and more so following resections of posterior fossa tumours. Here we report diffuse cerebral vasospasm in a child with hypoglossal nerve Schwannoma eight days following resection of the tumour.

Community consultation in emergency neurosurgical research: lessons from a proposed trial for patients with chronic subdural haematomas.

Chronic subdural haematoma (CSDH) is one of the most common neurosurgical disorders and is especially prevalent in old age. The subdural evacuating port system (SEPS) has emerged in the last few years as a minimally invasive alternative to the standard procedure of burr-hole evacuation. NHS practice is evidence-driven and evidence from high-quality clinical studies is required prior to implementation of any changes. In the UK, the National Research Ethics Service (NRES) advises community consultation prior to starting a clinical trial, where the patient is unlikely to have capacity to consent to enrolment in the trial. To prepare for a trial comparing minimally invasive (SEPS) versus burr-hole evacuation for evacuation of a CSDH, we have designed and undertaken a pre-protocol community consultation survey to examine potential patient participation. MATERIAL(S) AND METHODS: The study population consisted of patients, family members and carers/friends in neurosurgical clinic waiting rooms and wards at Addenbrooke's Hospital, Cambridge, who individually completed a questionnaire (n = 215).

Muscle and nerve biopsy for the neurosurgical trainee.

Nerve and muscle biopsy are common procedures often performed by junior surgical trainees. This educational review article describes the operative details of performing biopsies of muscle and nerve. Indications, pre-operative investigations and complication rates are described to aid in proper patient selection.

Ophthalmological outcome after resection of tumors based on the pineal gland.

Descriptions of visual dysfunction in pineal gland tumors tend to focus on upward gaze palsy alone. The authors aimed to characterize the nature, incidence, and functional significance of ophthalmological dysfunction after resection of tumors based on the pineal gland.

Image-guided resection of spheno-orbital skull-base meningiomas with predominant intraosseous component.

Although meningiomas of the spheno-orbital region commonly result in hyperostosis, intraosseous meningiomas, which feature extensive full thickness infiltration of the anterolateral skull base, are rare. In this study, we assess the value of image guidance during surgery for intraosseous spheno-orbital skull-base meningiomas in achieving safe and maximal abnormal bone resection.

Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations.

Meningiomas are among the most frequent intracranial tumors. The secretory variant of meningioma is characterized by glandular differentiation, formation of intracellular lumina and pseudopsammoma bodies, expression of a distinct pattern of cytokeratins and clinically by pronounced perifocal brain edema. Here we describe whole-exome sequencing analysis of DNA from 16 secretory meningiomas and corresponding constitutional tissues. All secretory meningiomas invariably harbored a mutation in both KLF4 and TRAF7. Validation in an independent cohort of 14 secretory meningiomas by Sanger sequencing or derived cleaved amplified polymorphic sequence (dCAPS) assay detected the same pattern, with KLF4 mutations observed in a total of 30/30 and TRAF7 mutations in 29/30 of these tumors. All KLF4 mutations were identical, affected codon 409 and resulted in a lysine to glutamine exchange (K409Q). KLF4 mutations were not found in 89 non-secretory meningiomas, 267 other intracranial tumors including gliomas, glioneuronal tumors, pituitary adenomas and metastases, 59 peripheral nerve sheath tumors and 52 pancreatic tumors. TRAF7 mutations were restricted to the WD40 domains. While KLF4 mutations were exclusively seen in secretory meningiomas, TRAF7 mutations were also observed in 7/89 (8 %) of non-secretory meningiomas. KLF4 and TRAF7 mutations were mutually exclusive with NF2 mutations. In conclusion, our findings suggest an essential contribution of combined KLF4 K409Q and TRAF7 mutations in the genesis of secretory meningioma and demonstrate a role for TRAF7 alterations in other non-NF2 meningiomas.

Role of surgery, radiotherapy and chemotherapy in papillary tumors of the pineal region: a multicenter study.

Papillary tumor of the pineal region (PTPR), recently described as a distinct clinicopathological entity, can show aggressive biological behavior. The optimal therapeutic approach of PTPR has not been well defined. The role of surgery, radiotherapy, and chemotherapy in the treatment of PTPR was analyzed in a large multicenter series. In order to determine factors that influence prognosis, outcome data of a series of 44 patients with histopathologically proven PTPR were retrospectively analyzed. Of the 44 patients, 32 were still alive after a median follow-up of 63.1 months. Twelve patients experienced progressive disease, with seven undergoing two relapses and five more than two. Median overall survival (OS) was not achieved. Median progression-free survival (PFS) was 58.1 months. Only gross total resection and younger age were associated with a longer OS, radiotherapy and chemotherapy having no significant impact. PFS was not influenced by gross total resection. Radiotherapy and chemotherapy had no significant effect. This retrospective series confirms the high risk of recurrence in PTPR and emphasizes the importance of gross total resection. However, our data provide no evidence for a role of adjuvant radiotherapy or chemotherapy in the treatment of PTPR.

How I do it--pineal surgery: supracerebellar infratentorial versus occipital transtentorial.

Resection of a pineal tumour requires fastidious pre-operative planning to select the optimal surgical approach and maximise resection while minimising morbidity.

Isolated hypoglossal schwannoma in a 9-year-old child.

The authors report a case of an isolated schwannoma of left hypoglossal nerve in a 9-year-old girl. To the authors' knowledge, this is the first case report of hypoglossal nerve schwannoma in the pediatric population in the absence of neurofibromatosis Type 2. The patient presented with a 2-month history of morning nausea and vomiting with occasional daytime headaches. Magnetic resonance imaging and subsequent CT scanning revealed a dumbbell tumor with a belly in the lower third of the posterior fossa and head underneath the left jugular foramen. Its neck protruded through an expanded hypoglossal canal. Although the lesion bore radiological characteristics of a hypoglossal schwannoma, the absence of hypoglossal palsy and the apparent lack of such tumors in the pediatric population the preoperative diagnosis was not certain. The tumor was approached via a midline suboccipital craniotomy, and gross-total resection was achieved. Pathological examination confirmed the diagnosis of schwannoma. Blood and tumor tests for mutations in the NF2 gene were negative. Postoperative mild hypoglossal palsy recovered by the 3-month follow-up, and an MRI study obtained at 1 year did not show recurrence.

Transient perioperative brainstem paralysis secondary to a local anesthetic.

Local anesthesia is widely used, in isolation or in conjunction with general anesthesia. The authors describe 2 adolescent patients presenting with absent brainstem reflexes and delayed awakening following elective foramen magnum decompression for Chiari Type I malformation. In both cases, neurological deficits were closely associated with the administration of a levobupivacaine field block following wound closure. In the absence of any structural or biochemical abnormalities, and with spontaneous recovery approximating the anesthetic half-life, the authors' observations are consistent with transient brainstem paralysis caused by perioperative local anesthetic infiltration.

Decompressive craniectomy - operative technique and perioperative care.

With improvements in neurocritical care advanced measures of treating raised intracranial pressure (ICP) are more frequently utilised. Decompressive craniectomy is an effective ICP-lowering procedure; however its benefits are maximised with optimal surgical technique and perioperative care, as well as by paying attention to possible complications. This article focuses on the current indications and rationale for decompressive craniectomy, and the surgical technique of bifrontal and unilateral decompression. The key surgical points include a large craniectomy window and opening of the dura, leaving it unsutured or performing a wide non-constricting duroplasty. Perioperative care and possible complications are also discussed.

Working toward rational and evidence-based treatment of chronic subdural hematoma.

Chronic subdural hematoma (CSDH) is one of the most common neurosurgical conditions that can usually be treated with relatively simple and effective surgical procedures. It affects primarily the elderly, a rising population worldwide. Together with improved awareness among the medical profession and greater access to modern imaging facilities, the incidence of CSDH is set to rise significantly. Maximization of the efficiency of management of CSDH is therefore a priority. To this end, a review of the findings of clinical and laboratory research underpinning the basis of the modern management of CSDH has been carried out. This review focuses on the pathophysiology and briefly discusses the epidemiology, clinical presentation, and surgical treatments of CSDH, concluding that a one-for-all management strategy is not appropriate. Creating rational bases for the selection of an ideal treatment strategy for an individual patient should be the target. This can be achieved through better understanding of the nature of the condition through systematic basic science research, ascertaining the merits of different surgical techniques in well-designed and rigorously executed clinical trials, using advances in imaging techniques to classify CSDH (a subject not addressed here), and training in and ongoing refinement of clinical acumen and surgical skills of individual surgeons.

Clinical assessment of cerebrospinal fluid dynamics in hydrocephalus. Guide to interpretation based on observational study.

The term hydrocephalus encompasses a range of disorders characterised by clinical symptoms, abnormal brain imaging and derangement of cerebrospinal fluid (CSF) dynamics. The ability to elucidate which patients would benefit from CSF diversion (a shunt or third ventriculostomy) is often unclear. Similar difficulties are often encountered in shunted patients to predict the scope for improvement by shunt re-adjustment or revision. In this study we aimed to update our knowledge of how key quantitative parameters describing CSF dynamics may be used in diagnosis of shunt-responsive hydrocephalus and in the assessment of shunt function.

The role of external drains and peritoneal conduits in the treatment of recurrent chronic subdural hematoma.

A considerable body of evidence supporting the use of external drainage after evacuation of primary chronic subdural hematoma (CSDH) exists in the literature. However, no systematic study of the value of postoperative drainage in the treatment of recurrent CSDH has been published. The aim of the study was to investigate external drains and subdural-to-peritoneal conduit in the treatment of recurrent CSDH.

Impact of duration of symptoms on CSF dynamics in idiopathic normal pressure hydrocephalus.

Cerebrospinal fluid (CSF) pressure-volume compensation may change over time as part of normal ageing, where the resistance to CSF outflow increases and the formation of CSF decreases with age. Is CSF compensation dependent on duration of symptoms in idiopathic normal pressure hydrocephalus (iNPH)?

GLO1-A novel amplified gene in human cancer.

To identify a novel amplified cancer gene a systematic screen of 975 human cancer DNA samples, 750 cell lines and 225 primary tumors, using the Affymetrix 10K SNP microarray was undertaken. The screen identified 193 amplicons. A previously uncharacterized amplicon located on 6p21.2 whose 1 Mb minimal common amplified region contained eight genes (GLO1, DNAH8, GLP1R, C6orf64, KCNK5, KCNK17, KCNK16, and C6orf102) was further investigated to determine which gene(s) are the biological targets of this amplicon. Real time quantitative PCR (qPCR) analysis of all amplicon 6p21.2 genes in 618 human cancer cell lines identified GLO1, encoding glyoxalase 1, to be the most frequently amplified gene [twofold or greater amplification in 8.4% (49/536) of cancers]. Also the association between amplification and overexpression was greatest for GLO1. RNAi knockdown of GLO1 had the greatest and most consistent impact on cell accumulation and apoptosis. Cell lines with GLO1 amplification were more sensitive to inhibition of GLO1 by bromobenzylglutathione cyclopentyl diester (BBGC). Subsequent qPCR of 520 primary tumor samples identified twofold and greater amplification of GLO1 in 8/37 (22%) of breast, 12/71 (17%) of sarcomas, 6/53 (11.3%) of nonsmall cell lung, 2/23 (8.7%) of bladder, 6/93 (6.5%) of renal and 5/83 (6%) of gastric cancers. Amplification of GLO1 was rare in colon cancer (1/35) and glioma (1/94). Collectively the results indicate that GLO1 is at least one of the targets of gene amplification on 6p21.2 and may represent a useful target for therapy in cancers with GLO1 amplification.

Imidazopurinones are markers of physiological genomic damage linked to DNA instability and glyoxalase 1-associated tumour multidrug resistance.

Glyoxal and methylglyoxal are reactive dicarbonyl metabolites formed and metabolized in physiological systems. Increased exposure to these dicarbonyls is linked to mutagenesis and cytotoxicity and enhanced dicarbonyl metabolism by overexpression of glyoxalase 1 is linked to tumour multidrug resistance in cancer chemotherapy. We report herein that glycation of DNA by glyoxal and methylglyoxal produces a quantitatively important class of nucleotide adduct in physiological systems-imidazopurinones. The adduct derived from methylglyoxal-3-(2'-deoxyribosyl)-6,7-dihydro-6,7-dihydroxy-6/7-methylimidazo-[2,3-b]purine-9(8)one isomers-was the major quantitative adduct detected in mononuclear leukocytes in vivo and tumour cell lines in vitro. It was linked to frequency of DNA strand breaks and increased markedly during apoptosis induced by a cell permeable glyoxalase 1 inhibitor. Unexpectedly, the DNA content of methylglyoxal-derived imidazopurinone and oxidative marker 7,8-dihydro-8-oxo-2'-deoxyguanosine were increased moderately in glyoxalase 1-linked multidrug resistant tumour cell lines. Together these findings suggest that imidazopurinones are a major type of endogenous DNA damage and glyoxalase 1 overexpression in tumour cells strives to counter increased imidazopurinone formation in tumour cells likely linked to their high glycolytic activity.

A census of amplified and overexpressed human cancer genes.

Integrated genome-wide screens of DNA copy number and gene expression in human cancers have accelerated the rate of discovery of amplified and overexpressed genes. However, the biological importance of most of the genes identified in such studies remains unclear. In this Analysis, we propose a weight-of-evidence based classification system for identifying individual genes in amplified regions that are selected for during tumour development. In a census of the published literature we have identified 77 genes for which there is good evidence of involvement in the development of human cancer.

PICNIC: an algorithm to predict absolute allelic copy number variation with microarray cancer data.

High-throughput oligonucleotide microarrays are commonly employed to investigate genetic disease, including cancer. The algorithms employed to extract genotypes and copy number variation function optimally for diploid genomes usually associated with inherited disease. However, cancer genomes are aneuploid in nature leading to systematic errors when using these techniques. We introduce a preprocessing transformation and hidden Markov model algorithm bespoke to cancer. This produces genotype classification, specification of regions of loss of heterozygosity, and absolute allelic copy number segmentation. Accurate prediction is demonstrated with a combination of independent experimental techniques. These methods are exemplified with affymetrix genome-wide SNP6.0 data from 755 cancer cell lines, enabling inference upon a number of features of biological interest. These data and the coded algorithm are freely available for download.

Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial.

Chronic subdural haematoma causes serious morbidity and mortality. It recurs after surgical evacuation in 5-30% of patients. Drains might reduce recurrence but are not used routinely. Our aim was to investigate the effect of drains on recurrence rates and clinical outcomes.

What constitutes Clinical Equipoise?

In order to incorporate patients ethically into randomised clinical trials, two related but distinct concepts are used: 'Clinical Equipoise' and the 'Uncertainty Principle'. We argue that true 'Clinical Equipoise', a consensus of opinion regarding valid treatment options, is a more valid way of recruiting to neurosurgical randomised clinical trials than the 'Uncertainty Principle', which reflects an individual clinician's uncertainty. This subtle distinction has implications for both recruitment and interpretation of the results of randomised clinical trials.

Arteriovenous malformations.

Arteriovenous malformations (AVMs) represent one of the most complex lesions encountered by the vascular neurosurgeon. They are thought to arise by a developmental aberration early in fetal life leading to structurally abnormal vessels, characterised by arteriovenous shunting. AVMs may present in a number of ways, the most devastating being hemorrhage. Their natural history, particularly hemorrhage risk, has been extensively studied and is crucial in informing management decisions. The primary goal of treatment is to eliminate hemorrhage risk. Success in treating these lesions involves comprehensive evaluation of the lesions to balance the risk of haemorrhage against the risk of treatment. Thus, first the decision whether to treat is made followed by selecting the optimum modality of treatment. Successful surgical treatment of AVMs requires extensive preoperative planning and meticulous microsurgical technique.

Paraganglioma of cauda equina.

The clinical, radiological and pathological features of a paraganglioma resulting in cauda equina syndrome are described, including magnetic resonance imaging features. The literature is reviewed and discussed.

Radiotherapy as an adjuvant in the management of intracranial meningiomas: are we practising evidence-based medicine?

Although increasingly used, the precise role of radiotherapy in the management of meningiomas is still disputed. The objective of this study, therefore, was to appraise the evidence for adjuvant radiotherapy in benign and atypical intracranial meningiomas, and to compare and contrast it with the current opinion and practice of neurosurgeons in the United Kingdom and the Republic of Ireland. The use of radiotherapy as a primary treatment strategy or its use in the treatment of recurrence was not considered. We performed a systematic review of the evidence for adjuvant radiotherapy in benign and atypical intracranial meningiomas, surveyed current opinion amongst neurosurgeons involved in such cases and ascertained local practice using data from the regional cancer registry. Overall, 10 cohorts were identified that fulfilled our eligibility criteria. Four studies showed significantly improved local control in patients receiving adjuvant radiotherapy for incompletely resected grade I meningiomas. Our survey demonstrated that the vast majority (98%) of neurosurgeons would not recommend adjuvant radiotherapy in grade I meningioma. In grade II meningioma, most (80%) would not advocate adjuvant radiotherapy if completely excised, but the majority (59%) would recommend radiotherapy in cases of subtotal resection. Significant variation in opinion between centres exists, however, particularly in cases of completely resected atypical meningiomas (p = 0.02). Data from the Eastern Cancer Registration and Information Centre appears to be in line with these findings: less than 10% of patients with grade I meningiomas, but almost 30% of patients with grade II meningiomas received adjuvant radiotherapy in the Eastern region. In conclusion, our study has highlighted significant variation in opinion and practice, reflecting a lack of class 1 evidence to support the use of adjuvant radiotherapy in the treatment of meningiomas. Efforts are underway to address this with a randomized multicentre trial comparing a policy of watchful waiting versus adjuvant irradiation.

The management of primary chronic subdural haematoma: a questionnaire survey of practice in the United Kingdom and the Republic of Ireland.

A wide range of treatment modalities are employed in the treatment of chronic subdural haematoma (CSDH). A rational and evidence-based treatment strategy has the potential to optimise treatment for the individual patient and save resources. The aim of this study was to survey aspects of current practice in the UK and Ireland. A 1-page postal questionnaire addressing the treatment of primary (i.e. not recurrent) CSDH was sent to consultant SBNS members in March 2006. There were 112 responses from 215 questionnaires (52%). The preferred surgical technique was burr hole drainage (92%). Most surgeons prefer not to place a drain, with 27% never using one and 58% using drain only in one-quarter of cases or less. Only 11% of surgeons always place a drain, and only 30% place one in 75% of cases or more. The closed subdural-to-external drainage was most commonly used (91%) with closed subgaleal-to-external and subdural-to-peritoneal conduit used less often (3 and 4%, respectively). Only 5% of responders claimed to know the exact recurrence rate. The average perceived recurrence rate among the surgeons that never use drains and those who always use drains, was the same (both 11%). Most operations are performed by registrars (77%). Postoperative imaging is requested routinely by 32% of respondents and 57% of surgeons prescribe bed rest. Ninety four per cent surgeons employ conservative management in less than one-quarter of cases. Forty-two per cent of surgeons never prescribe steroids, 55% prescribe them to those managed conservatively. This survey demonstrates that there are diverse practices in the management of CSDH. This may be because of sufficiently persuasive evidence either does not exist or is not always taken into account. The current literature provides Class II and III evidence and there is a need for randomized studies to address the role of external drainage, steroids and postoperative bed rest.

Stereoscopic Three-Dimensional Neuroanatomy Lectures Enhance Neurosurgical Training: Prospective Comparison with Traditional Teaching.

Stereoscopic three-dimensional (3D) imaging is increasingly used in the teaching of neuroanatomy and although this is mainly aimed at undergraduate medical students, it has enormous potential for enhancing the training of neurosurgeons. This study aims to assess whether 3D lecturing is an effective method of enhancing the knowledge and confidence of neurosurgeons and how it compares with traditional two-dimensional (2D) lecturing and cadaveric training.

Methodological shortcomings in the literature evaluating the role and applications of 3D training for surgical trainees.

There has been an increased interest in the use of three-dimensional (3D) technology in surgical training. We wish to appraise the methodological rigor applied to evaluating the role and applications of 3D technology in surgical training, in particular, on the validity of these models and assessment methods in simulated surgical training.

Correlation of volumetric growth and histological grade in 50 meningiomas.

Advances in radiological imaging techniques have enabled volumetric measurements of meningiomas to be easily monitored using serial imaging scans. There is limited literature on the relationship between tumour growth rates and the WHO classification of meningiomas despite tumour growth being a major determinant of type and timing of intervention. Volumetric growth has been successfully used to assess growth of low-grade glioma; however, there is limited information on the volumetric growth rate (VGR) of meningiomas. This study aimed to determine the reliability of VGR measurement in patients with meningioma, assess the relationship between VGR and 2016 WHO grading as well as clinical applicability of VGR in monitoring meningioma growth.

Survey on current cognitive practices within the European Low-Grade Glioma Network: towards a European assessment protocol.

The European Low-Grade Glioma network indicated a need to better understand common practices regarding the managing of diffuse low-grade gliomas. This area has experienced great advances in recent years.

Concomitant Primary CNS Lymphoma and FSH-Pituitary Adenoma Arising Within the Sella. Entirely Coincidental?

Collision tumors are the simultaneous occurrence of more than one type of neoplasm within an anatomic space. In the pituitary sella, collision tumors are exceedingly rare, and not much is known about their etiology and prognosis.

Improved long-term survival with subdural drains following evacuation of chronic subdural haematoma.

Chronic subdural haematoma (CSDH) is a common condition that is effectively managed by burrhole drainage but requires repeat surgery in a significant minority of patients. The Cambridge Chronic Subdural Haematoma Trial (CCSHT) was a randomised controlled study that showed placement of subdural drains for 48 h following burrhole evacuation significantly reduces the incidence of reoperation and improves survival at 6 months. The present study examined the long-term survival of the patients in the trial.

The Effect of 3-Dimensional Simulation on Neurosurgical Skill Acquisition and Surgical Performance: A Review of the Literature.

In recent years, 3-dimensional (3D) simulation of neurosurgical procedures has become increasingly popular as an addition to training programmes. However, there remains little objective evidence of its effectiveness in improving live surgical skill. This review analysed the current literature in 3D neurosurgical simulation, highlighting remaining gaps in the evidence base for improvement in surgical performance and suggests useful future research directions.

Clinical Experience and Results of Microsurgical Resection of Arterioveonous Malformation in the Presence of Space-Occupying Intracerebral Hematoma.

Management of ruptured arteriovenous malformations (AVMs) with a mass-producing intracerebral hematoma (ICH) represents a surgical dilemma.

Volumetric growth rates of meningioma and its correlation with histological diagnosis and clinical outcome: a systematic review.

Tumour growth has been used to successfully predict progression-free survival in low-grade glioma. This systematic review sought to establish the evidence base regarding the correlation of volumetric growth rates with histological diagnosis and potential to predict clinical outcome in patients with meningioma.

Reporting of patient-reported health-related quality of life in adults with diffuse low-grade glioma: a systematic review.

Patient-reported health-related quality of life (HRQoL) analysis can provide important information for managing the balance between treatment benefits and treatment-related adverse effects on quality of life (QoL). This systematic review sought to identify the range of HRQoL measures used for patients with diffuse hemispheric WHO grade II glioma (DLGG) and assess the quality of HRQoL reporting.

Core Outcomes and Common Data Elements in Chronic Subdural Hematoma: A Systematic Review of the Literature Focusing on Baseline and Peri-Operative Care Data Elements.

Chronic subdural hematoma (CSDH) is an increasingly common subtype of head injury, especially in the elderly population. The optimization of treatment strategies has been hampered by the collection of heterogeneous outcome measures and data elements, precluding cross-study comparisons. This study aimed to quantify the heterogeneity of data elements in the pre-operative, operative, and post-operative phases of care, and build the basis for the development of a set of common data elements (CDEs) for CSDH. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered with the PROSPERO register of systematic reviews (CRD42014007266). All full-text English studies with more than 10 patients (prospective) or more than 100 patients (retrospective) published after 1990 examining clinical outcomes in CSDH were eligible for inclusion. One hundred two eligible studies were found. Only 40 studies (39.2%) reported the main presenting symptom/feature and 24 (23.5%) reported additional symptoms/features. Admitting neurological/functional status was classified by the Glasgow Coma Scale (25 studies; 24.5%), the Markwalder Score (26 studies; 25.5%) and the modified Rankin Scale (three studies; 2.9%). Fifty-four studies (52.9%) made some mention of patient comorbidities and 58 studies (56.9%) reported the proportion or excluded patients on anticoagulant medication. Eighteen studies (17.6%) reported baseline coagulation status. Sixty-four studies (62.7%) stratified or assessed severity based on radiological findings, although the methods used varied widely. There was variable reporting of surgical technique and post-operative care; 32 studies (31.4%) made no mention of whether the operations were performed under general or local anesthetic. This study, a part of the Core Outcomes and Common Data Elements in CSDH (CODE-CSDH) project, confirms and quantifies the heterogeneity of data elements collected and reported in CSDH studies to date. It establishes the basis for the consensus-based development of a set of common data elements, facilitating robust cross-study comparisons and resulting improvements in patient outcomes.

Germinoma of the medulla oblongata - A case report.

We describe a case of primary intracranial medulla oblongata germinoma in a 23-year-old female who presented with deteriorating balance and mobility. Imaging demonstrated an exophytic lesion arising from the dorsal medulla oblongata and extending into the fourth ventricle. The tissue sample was obtained via suboccipital craniotomy and a diagnosis of a primary medullary germinoma was made. The patient underwent whole craniospinal axis radiotherapy and remains well and recurrence-free at 1-year follow up.

Core Outcomes and Common Data Elements in Chronic Subdural Hematoma: A Systematic Review of the Literature Focusing on Reported Outcomes.

The plethora of studies in chronic subdural hematoma (CSDH) has not resulted in the development of an evidence-based treatment strategy, largely due to heterogeneous outcome measures that preclude cross-study comparisons and guideline development. This study aimed to identify and quantify the heterogeneity of outcome measures reported in the CSDH literature and to build a case for the development of a consensus-based core outcome set. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered with the PROSPERO international prospective register of systematic reviews (CRD42014007266). All full-text English language studies with >10 patients (prospective) or >100 patients (retrospective) published after 1990 examining clinical outcomes in CSDH were eligible for inclusion. One hundred two eligible studies were found. There were 14 (13.7%) randomized controlled trials, one single arm trial (1.0%), 25 (24.5%) cohort comparison studies, and 62 (60.8%) prospective or retrospective cohort studies. Outcome domains reported by the studies included mortality (63.8% of included studies), recurrence (94.1%), complications (48.0%), functional outcomes (40.2%), and radiological (38.2%) outcomes. There was significant heterogeneity in the definitions of the outcome measures, as evidenced by the seven different definitions of the term "recurrence," with no definition given in 19 studies. The time-points of assessment for all the outcome domains varied greatly from inpatient/hospital discharge to 18 months. This study establishes and quantifies the heterogeneity of outcome measure reporting in CSDH and builds the case for the development of a robust consensus-based core outcome set for future studies to adhere to as part of the Core Outcomes and Common Data Elements in CSDH (CODE-CSDH) project.

Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer.

Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C > T and A > G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. A number of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria and is fundamentally linked to mtDNA replication.

Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey.

Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children.

Chronic subdural haematoma: modern management and emerging therapies.

Chronic subdural haematoma (CSDH) is one of the most common neurological disorders, and is especially prevalent among elderly individuals. Surgical evacuation is the mainstay of management for symptomatic patients or haematomas exerting significant mass effect. Although burr hole craniostomy is the most widely practised technique worldwide, approximately 10-20% of surgically treated patients experience postoperative recurrence necessitating reoperation. Given the increasing incidence of CSDH in a growing elderly population, a need exists for refined techniques that combine a minimally invasive approach with clinical efficacy and cost-effectiveness. In addition, nonsurgical treatment modalities, such as steroids, are attracting considerable interest, as they have the potential to reduce postoperative recurrence or even replace the need for surgery in selected patients. This Review provides an overview of the contemporary management of CSDH and presents considerations regarding future approaches that could further optimize patient care and outcomes.

Alternative cost-effective method to record 3D intra-operative images: a technical note.

The educational value of stereoscopic imaging in neurosurgical training has increasingly been appreciated and its use increased during the last decade. We describe a technique that we developed to acquire and reproduce intra-operative stereoscopic images.

Current concepts in the surgical management of glioma patients.

The scientific basis for the surgical management of patients with glioma is rapidly evolving. The infiltrative nature of these cancers precludes a surgical cure, but despite this, cytoreductive surgery remains central to high-quality patient care. In addition to tissue sampling for accurate histopathological diagnosis and molecular genetic characterisation, clinical benefit from decompression of space-occupying lesions and microsurgical cytoreduction has been reported in patients with different grades of glioma. By integrating advanced surgical techniques with molecular genetic characterisation of the disease and targeted radiotherapy and chemotherapy, it is possible to construct a programme of personalised surgical therapy throughout the patient journey. The goal of therapeutic packages tailored to each patient is to optimise patient safety and clinical outcome and must be delivered in a multidisciplinary setting. Here we review the current concepts that underlie surgical subspecialisation in the management of patients with glioma.

Twist-drill craniostomy with hollow screws for evacuation of chronic subdural hematoma.

OBJECT.: The incidence of chronic subdural hematoma (CSDH) is expected to increase substantially over the next 25 years. Continuing refinement of techniques for surgical evacuation is essential for optimizing patient outcomes. A novel technique involving a hollow screw, which is threaded through a twist-drill hole in the cranium and then connected to a closed drainage system, has been increasing in popularity. The aim of this systematic review is to collate and analyze the published experience with this novel technique and to evaluate its efficacy in comparison with the other surgical treatment methods.

Processed pseudogenes acquired somatically during cancer development.

Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5' truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context.

Delayed neurological deficit following resection of tuberculum sellae meningioma: report of two cases, one with permanent and one with reversible visual impairment.

The most common presentation of patients with tuberculum sellae meningiomas is visual loss, and surgical resection is the main mode of treatment. Preservation of vision is not only the main objective of the surgery; loss of vision is also its main risk. Visual deterioration following surgery is usually apparent immediately post-operatively. Here we present two cases of patients who underwent resection of tuberculum sellae meningioma and whose vision following surgery was initially unchanged until the postoperative day two when dramatic visual deterioration occurred. In the first case this resulted in blindness, whereas in the second case vision recovered back to the preoperative state. The possible mechanisms of visual deterioration and modes of treatment are discussed.

Giant intracranial hemangioma in a neonate.

In this report we detail the case of an infant presenting with a giant intracranial congenital hemangioma and describe the clinical features and surgical management. Congenital hemangiomas are benign vascular tumors that typically present as skin lesions in neonates and infants. On rare occasions they present as intracranial tumors. The possibility that these tumors may undergo spontaneous regression poses a treatment dilemma.

Diffuse cerebral vasospasm following resection of a hypoglossal schwannoma in a child.

Diffuse cerebral vasospasm is a rare complication following tumour resection. This phenomenon seems to be even rarer in the paediatric population and more so following resections of posterior fossa tumours. Here we report diffuse cerebral vasospasm in a child with hypoglossal nerve Schwannoma eight days following resection of the tumour.

Community consultation in emergency neurosurgical research: lessons from a proposed trial for patients with chronic subdural haematomas.

Chronic subdural haematoma (CSDH) is one of the most common neurosurgical disorders and is especially prevalent in old age. The subdural evacuating port system (SEPS) has emerged in the last few years as a minimally invasive alternative to the standard procedure of burr-hole evacuation. NHS practice is evidence-driven and evidence from high-quality clinical studies is required prior to implementation of any changes. In the UK, the National Research Ethics Service (NRES) advises community consultation prior to starting a clinical trial, where the patient is unlikely to have capacity to consent to enrolment in the trial. To prepare for a trial comparing minimally invasive (SEPS) versus burr-hole evacuation for evacuation of a CSDH, we have designed and undertaken a pre-protocol community consultation survey to examine potential patient participation. MATERIAL(S) AND METHODS: The study population consisted of patients, family members and carers/friends in neurosurgical clinic waiting rooms and wards at Addenbrooke's Hospital, Cambridge, who individually completed a questionnaire (n = 215).

Muscle and nerve biopsy for the neurosurgical trainee.

Nerve and muscle biopsy are common procedures often performed by junior surgical trainees. This educational review article describes the operative details of performing biopsies of muscle and nerve. Indications, pre-operative investigations and complication rates are described to aid in proper patient selection.

Ophthalmological outcome after resection of tumors based on the pineal gland.

Descriptions of visual dysfunction in pineal gland tumors tend to focus on upward gaze palsy alone. The authors aimed to characterize the nature, incidence, and functional significance of ophthalmological dysfunction after resection of tumors based on the pineal gland.

Image-guided resection of spheno-orbital skull-base meningiomas with predominant intraosseous component.

Although meningiomas of the spheno-orbital region commonly result in hyperostosis, intraosseous meningiomas, which feature extensive full thickness infiltration of the anterolateral skull base, are rare. In this study, we assess the value of image guidance during surgery for intraosseous spheno-orbital skull-base meningiomas in achieving safe and maximal abnormal bone resection.

Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations.

Meningiomas are among the most frequent intracranial tumors. The secretory variant of meningioma is characterized by glandular differentiation, formation of intracellular lumina and pseudopsammoma bodies, expression of a distinct pattern of cytokeratins and clinically by pronounced perifocal brain edema. Here we describe whole-exome sequencing analysis of DNA from 16 secretory meningiomas and corresponding constitutional tissues. All secretory meningiomas invariably harbored a mutation in both KLF4 and TRAF7. Validation in an independent cohort of 14 secretory meningiomas by Sanger sequencing or derived cleaved amplified polymorphic sequence (dCAPS) assay detected the same pattern, with KLF4 mutations observed in a total of 30/30 and TRAF7 mutations in 29/30 of these tumors. All KLF4 mutations were identical, affected codon 409 and resulted in a lysine to glutamine exchange (K409Q). KLF4 mutations were not found in 89 non-secretory meningiomas, 267 other intracranial tumors including gliomas, glioneuronal tumors, pituitary adenomas and metastases, 59 peripheral nerve sheath tumors and 52 pancreatic tumors. TRAF7 mutations were restricted to the WD40 domains. While KLF4 mutations were exclusively seen in secretory meningiomas, TRAF7 mutations were also observed in 7/89 (8 %) of non-secretory meningiomas. KLF4 and TRAF7 mutations were mutually exclusive with NF2 mutations. In conclusion, our findings suggest an essential contribution of combined KLF4 K409Q and TRAF7 mutations in the genesis of secretory meningioma and demonstrate a role for TRAF7 alterations in other non-NF2 meningiomas.

Role of surgery, radiotherapy and chemotherapy in papillary tumors of the pineal region: a multicenter study.

Papillary tumor of the pineal region (PTPR), recently described as a distinct clinicopathological entity, can show aggressive biological behavior. The optimal therapeutic approach of PTPR has not been well defined. The role of surgery, radiotherapy, and chemotherapy in the treatment of PTPR was analyzed in a large multicenter series. In order to determine factors that influence prognosis, outcome data of a series of 44 patients with histopathologically proven PTPR were retrospectively analyzed. Of the 44 patients, 32 were still alive after a median follow-up of 63.1 months. Twelve patients experienced progressive disease, with seven undergoing two relapses and five more than two. Median overall survival (OS) was not achieved. Median progression-free survival (PFS) was 58.1 months. Only gross total resection and younger age were associated with a longer OS, radiotherapy and chemotherapy having no significant impact. PFS was not influenced by gross total resection. Radiotherapy and chemotherapy had no significant effect. This retrospective series confirms the high risk of recurrence in PTPR and emphasizes the importance of gross total resection. However, our data provide no evidence for a role of adjuvant radiotherapy or chemotherapy in the treatment of PTPR.

How I do it--pineal surgery: supracerebellar infratentorial versus occipital transtentorial.

Resection of a pineal tumour requires fastidious pre-operative planning to select the optimal surgical approach and maximise resection while minimising morbidity.

Isolated hypoglossal schwannoma in a 9-year-old child.

The authors report a case of an isolated schwannoma of left hypoglossal nerve in a 9-year-old girl. To the authors' knowledge, this is the first case report of hypoglossal nerve schwannoma in the pediatric population in the absence of neurofibromatosis Type 2. The patient presented with a 2-month history of morning nausea and vomiting with occasional daytime headaches. Magnetic resonance imaging and subsequent CT scanning revealed a dumbbell tumor with a belly in the lower third of the posterior fossa and head underneath the left jugular foramen. Its neck protruded through an expanded hypoglossal canal. Although the lesion bore radiological characteristics of a hypoglossal schwannoma, the absence of hypoglossal palsy and the apparent lack of such tumors in the pediatric population the preoperative diagnosis was not certain. The tumor was approached via a midline suboccipital craniotomy, and gross-total resection was achieved. Pathological examination confirmed the diagnosis of schwannoma. Blood and tumor tests for mutations in the NF2 gene were negative. Postoperative mild hypoglossal palsy recovered by the 3-month follow-up, and an MRI study obtained at 1 year did not show recurrence.

Transient perioperative brainstem paralysis secondary to a local anesthetic.

Local anesthesia is widely used, in isolation or in conjunction with general anesthesia. The authors describe 2 adolescent patients presenting with absent brainstem reflexes and delayed awakening following elective foramen magnum decompression for Chiari Type I malformation. In both cases, neurological deficits were closely associated with the administration of a levobupivacaine field block following wound closure. In the absence of any structural or biochemical abnormalities, and with spontaneous recovery approximating the anesthetic half-life, the authors' observations are consistent with transient brainstem paralysis caused by perioperative local anesthetic infiltration.

Decompressive craniectomy - operative technique and perioperative care.

With improvements in neurocritical care advanced measures of treating raised intracranial pressure (ICP) are more frequently utilised. Decompressive craniectomy is an effective ICP-lowering procedure; however its benefits are maximised with optimal surgical technique and perioperative care, as well as by paying attention to possible complications. This article focuses on the current indications and rationale for decompressive craniectomy, and the surgical technique of bifrontal and unilateral decompression. The key surgical points include a large craniectomy window and opening of the dura, leaving it unsutured or performing a wide non-constricting duroplasty. Perioperative care and possible complications are also discussed.

Working toward rational and evidence-based treatment of chronic subdural hematoma.

Chronic subdural hematoma (CSDH) is one of the most common neurosurgical conditions that can usually be treated with relatively simple and effective surgical procedures. It affects primarily the elderly, a rising population worldwide. Together with improved awareness among the medical profession and greater access to modern imaging facilities, the incidence of CSDH is set to rise significantly. Maximization of the efficiency of management of CSDH is therefore a priority. To this end, a review of the findings of clinical and laboratory research underpinning the basis of the modern management of CSDH has been carried out. This review focuses on the pathophysiology and briefly discusses the epidemiology, clinical presentation, and surgical treatments of CSDH, concluding that a one-for-all management strategy is not appropriate. Creating rational bases for the selection of an ideal treatment strategy for an individual patient should be the target. This can be achieved through better understanding of the nature of the condition through systematic basic science research, ascertaining the merits of different surgical techniques in well-designed and rigorously executed clinical trials, using advances in imaging techniques to classify CSDH (a subject not addressed here), and training in and ongoing refinement of clinical acumen and surgical skills of individual surgeons.

Clinical assessment of cerebrospinal fluid dynamics in hydrocephalus. Guide to interpretation based on observational study.

The term hydrocephalus encompasses a range of disorders characterised by clinical symptoms, abnormal brain imaging and derangement of cerebrospinal fluid (CSF) dynamics. The ability to elucidate which patients would benefit from CSF diversion (a shunt or third ventriculostomy) is often unclear. Similar difficulties are often encountered in shunted patients to predict the scope for improvement by shunt re-adjustment or revision. In this study we aimed to update our knowledge of how key quantitative parameters describing CSF dynamics may be used in diagnosis of shunt-responsive hydrocephalus and in the assessment of shunt function.

Causes of neurological deficits following clipping of 200 consecutive ruptured aneurysms in patients with good-grade aneurysmal subarachnoid haemorrhage.

The surgical risk of unruptured aneurysms is well quantified. Although the outcomes for ruptured aneurysms are also well described, due to the concurrent morbidity from the natural history of the haemorrhage, the relative contributions of surgery and natural history to outcome following aneurysmal subarachnoid haemorrhage (SAH) is not. Our aim was to quantify these risks.

The role of external drains and peritoneal conduits in the treatment of recurrent chronic subdural hematoma.

A considerable body of evidence supporting the use of external drainage after evacuation of primary chronic subdural hematoma (CSDH) exists in the literature. However, no systematic study of the value of postoperative drainage in the treatment of recurrent CSDH has been published. The aim of the study was to investigate external drains and subdural-to-peritoneal conduit in the treatment of recurrent CSDH.

Impact of duration of symptoms on CSF dynamics in idiopathic normal pressure hydrocephalus.

Cerebrospinal fluid (CSF) pressure-volume compensation may change over time as part of normal ageing, where the resistance to CSF outflow increases and the formation of CSF decreases with age. Is CSF compensation dependent on duration of symptoms in idiopathic normal pressure hydrocephalus (iNPH)?

GLO1-A novel amplified gene in human cancer.

To identify a novel amplified cancer gene a systematic screen of 975 human cancer DNA samples, 750 cell lines and 225 primary tumors, using the Affymetrix 10K SNP microarray was undertaken. The screen identified 193 amplicons. A previously uncharacterized amplicon located on 6p21.2 whose 1 Mb minimal common amplified region contained eight genes (GLO1, DNAH8, GLP1R, C6orf64, KCNK5, KCNK17, KCNK16, and C6orf102) was further investigated to determine which gene(s) are the biological targets of this amplicon. Real time quantitative PCR (qPCR) analysis of all amplicon 6p21.2 genes in 618 human cancer cell lines identified GLO1, encoding glyoxalase 1, to be the most frequently amplified gene [twofold or greater amplification in 8.4% (49/536) of cancers]. Also the association between amplification and overexpression was greatest for GLO1. RNAi knockdown of GLO1 had the greatest and most consistent impact on cell accumulation and apoptosis. Cell lines with GLO1 amplification were more sensitive to inhibition of GLO1 by bromobenzylglutathione cyclopentyl diester (BBGC). Subsequent qPCR of 520 primary tumor samples identified twofold and greater amplification of GLO1 in 8/37 (22%) of breast, 12/71 (17%) of sarcomas, 6/53 (11.3%) of nonsmall cell lung, 2/23 (8.7%) of bladder, 6/93 (6.5%) of renal and 5/83 (6%) of gastric cancers. Amplification of GLO1 was rare in colon cancer (1/35) and glioma (1/94). Collectively the results indicate that GLO1 is at least one of the targets of gene amplification on 6p21.2 and may represent a useful target for therapy in cancers with GLO1 amplification.

Imidazopurinones are markers of physiological genomic damage linked to DNA instability and glyoxalase 1-associated tumour multidrug resistance.

Glyoxal and methylglyoxal are reactive dicarbonyl metabolites formed and metabolized in physiological systems. Increased exposure to these dicarbonyls is linked to mutagenesis and cytotoxicity and enhanced dicarbonyl metabolism by overexpression of glyoxalase 1 is linked to tumour multidrug resistance in cancer chemotherapy. We report herein that glycation of DNA by glyoxal and methylglyoxal produces a quantitatively important class of nucleotide adduct in physiological systems-imidazopurinones. The adduct derived from methylglyoxal-3-(2'-deoxyribosyl)-6,7-dihydro-6,7-dihydroxy-6/7-methylimidazo-[2,3-b]purine-9(8)one isomers-was the major quantitative adduct detected in mononuclear leukocytes in vivo and tumour cell lines in vitro. It was linked to frequency of DNA strand breaks and increased markedly during apoptosis induced by a cell permeable glyoxalase 1 inhibitor. Unexpectedly, the DNA content of methylglyoxal-derived imidazopurinone and oxidative marker 7,8-dihydro-8-oxo-2'-deoxyguanosine were increased moderately in glyoxalase 1-linked multidrug resistant tumour cell lines. Together these findings suggest that imidazopurinones are a major type of endogenous DNA damage and glyoxalase 1 overexpression in tumour cells strives to counter increased imidazopurinone formation in tumour cells likely linked to their high glycolytic activity.

A census of amplified and overexpressed human cancer genes.

Integrated genome-wide screens of DNA copy number and gene expression in human cancers have accelerated the rate of discovery of amplified and overexpressed genes. However, the biological importance of most of the genes identified in such studies remains unclear. In this Analysis, we propose a weight-of-evidence based classification system for identifying individual genes in amplified regions that are selected for during tumour development. In a census of the published literature we have identified 77 genes for which there is good evidence of involvement in the development of human cancer.

PICNIC: an algorithm to predict absolute allelic copy number variation with microarray cancer data.

High-throughput oligonucleotide microarrays are commonly employed to investigate genetic disease, including cancer. The algorithms employed to extract genotypes and copy number variation function optimally for diploid genomes usually associated with inherited disease. However, cancer genomes are aneuploid in nature leading to systematic errors when using these techniques. We introduce a preprocessing transformation and hidden Markov model algorithm bespoke to cancer. This produces genotype classification, specification of regions of loss of heterozygosity, and absolute allelic copy number segmentation. Accurate prediction is demonstrated with a combination of independent experimental techniques. These methods are exemplified with affymetrix genome-wide SNP6.0 data from 755 cancer cell lines, enabling inference upon a number of features of biological interest. These data and the coded algorithm are freely available for download.

Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial.

Chronic subdural haematoma causes serious morbidity and mortality. It recurs after surgical evacuation in 5-30% of patients. Drains might reduce recurrence but are not used routinely. Our aim was to investigate the effect of drains on recurrence rates and clinical outcomes.

What constitutes Clinical Equipoise?

In order to incorporate patients ethically into randomised clinical trials, two related but distinct concepts are used: 'Clinical Equipoise' and the 'Uncertainty Principle'. We argue that true 'Clinical Equipoise', a consensus of opinion regarding valid treatment options, is a more valid way of recruiting to neurosurgical randomised clinical trials than the 'Uncertainty Principle', which reflects an individual clinician's uncertainty. This subtle distinction has implications for both recruitment and interpretation of the results of randomised clinical trials.

Arteriovenous malformations.

Arteriovenous malformations (AVMs) represent one of the most complex lesions encountered by the vascular neurosurgeon. They are thought to arise by a developmental aberration early in fetal life leading to structurally abnormal vessels, characterised by arteriovenous shunting. AVMs may present in a number of ways, the most devastating being hemorrhage. Their natural history, particularly hemorrhage risk, has been extensively studied and is crucial in informing management decisions. The primary goal of treatment is to eliminate hemorrhage risk. Success in treating these lesions involves comprehensive evaluation of the lesions to balance the risk of haemorrhage against the risk of treatment. Thus, first the decision whether to treat is made followed by selecting the optimum modality of treatment. Successful surgical treatment of AVMs requires extensive preoperative planning and meticulous microsurgical technique.

Paraganglioma of cauda equina.

The clinical, radiological and pathological features of a paraganglioma resulting in cauda equina syndrome are described, including magnetic resonance imaging features. The literature is reviewed and discussed.

Radiotherapy as an adjuvant in the management of intracranial meningiomas: are we practising evidence-based medicine?

Although increasingly used, the precise role of radiotherapy in the management of meningiomas is still disputed. The objective of this study, therefore, was to appraise the evidence for adjuvant radiotherapy in benign and atypical intracranial meningiomas, and to compare and contrast it with the current opinion and practice of neurosurgeons in the United Kingdom and the Republic of Ireland. The use of radiotherapy as a primary treatment strategy or its use in the treatment of recurrence was not considered. We performed a systematic review of the evidence for adjuvant radiotherapy in benign and atypical intracranial meningiomas, surveyed current opinion amongst neurosurgeons involved in such cases and ascertained local practice using data from the regional cancer registry. Overall, 10 cohorts were identified that fulfilled our eligibility criteria. Four studies showed significantly improved local control in patients receiving adjuvant radiotherapy for incompletely resected grade I meningiomas. Our survey demonstrated that the vast majority (98%) of neurosurgeons would not recommend adjuvant radiotherapy in grade I meningioma. In grade II meningioma, most (80%) would not advocate adjuvant radiotherapy if completely excised, but the majority (59%) would recommend radiotherapy in cases of subtotal resection. Significant variation in opinion between centres exists, however, particularly in cases of completely resected atypical meningiomas (p = 0.02). Data from the Eastern Cancer Registration and Information Centre appears to be in line with these findings: less than 10% of patients with grade I meningiomas, but almost 30% of patients with grade II meningiomas received adjuvant radiotherapy in the Eastern region. In conclusion, our study has highlighted significant variation in opinion and practice, reflecting a lack of class 1 evidence to support the use of adjuvant radiotherapy in the treatment of meningiomas. Efforts are underway to address this with a randomized multicentre trial comparing a policy of watchful waiting versus adjuvant irradiation.

The management of primary chronic subdural haematoma: a questionnaire survey of practice in the United Kingdom and the Republic of Ireland.

A wide range of treatment modalities are employed in the treatment of chronic subdural haematoma (CSDH). A rational and evidence-based treatment strategy has the potential to optimise treatment for the individual patient and save resources. The aim of this study was to survey aspects of current practice in the UK and Ireland. A 1-page postal questionnaire addressing the treatment of primary (i.e. not recurrent) CSDH was sent to consultant SBNS members in March 2006. There were 112 responses from 215 questionnaires (52%). The preferred surgical technique was burr hole drainage (92%). Most surgeons prefer not to place a drain, with 27% never using one and 58% using drain only in one-quarter of cases or less. Only 11% of surgeons always place a drain, and only 30% place one in 75% of cases or more. The closed subdural-to-external drainage was most commonly used (91%) with closed subgaleal-to-external and subdural-to-peritoneal conduit used less often (3 and 4%, respectively). Only 5% of responders claimed to know the exact recurrence rate. The average perceived recurrence rate among the surgeons that never use drains and those who always use drains, was the same (both 11%). Most operations are performed by registrars (77%). Postoperative imaging is requested routinely by 32% of respondents and 57% of surgeons prescribe bed rest. Ninety four per cent surgeons employ conservative management in less than one-quarter of cases. Forty-two per cent of surgeons never prescribe steroids, 55% prescribe them to those managed conservatively. This survey demonstrates that there are diverse practices in the management of CSDH. This may be because of sufficiently persuasive evidence either does not exist or is not always taken into account. The current literature provides Class II and III evidence and there is a need for randomized studies to address the role of external drainage, steroids and postoperative bed rest.

Stereoscopic Three-Dimensional Neuroanatomy Lectures Enhance Neurosurgical Training: Prospective Comparison with Traditional Teaching.

Stereoscopic three-dimensional (3D) imaging is increasingly used in the teaching of neuroanatomy and although this is mainly aimed at undergraduate medical students, it has enormous potential for enhancing the training of neurosurgeons. This study aims to assess whether 3D lecturing is an effective method of enhancing the knowledge and confidence of neurosurgeons and how it compares with traditional two-dimensional (2D) lecturing and cadaveric training.

Methodological shortcomings in the literature evaluating the role and applications of 3D training for surgical trainees.

There has been an increased interest in the use of three-dimensional (3D) technology in surgical training. We wish to appraise the methodological rigor applied to evaluating the role and applications of 3D technology in surgical training, in particular, on the validity of these models and assessment methods in simulated surgical training.

Correlation of volumetric growth and histological grade in 50 meningiomas.

Advances in radiological imaging techniques have enabled volumetric measurements of meningiomas to be easily monitored using serial imaging scans. There is limited literature on the relationship between tumour growth rates and the WHO classification of meningiomas despite tumour growth being a major determinant of type and timing of intervention. Volumetric growth has been successfully used to assess growth of low-grade glioma; however, there is limited information on the volumetric growth rate (VGR) of meningiomas. This study aimed to determine the reliability of VGR measurement in patients with meningioma, assess the relationship between VGR and 2016 WHO grading as well as clinical applicability of VGR in monitoring meningioma growth.

Survey on current cognitive practices within the European Low-Grade Glioma Network: towards a European assessment protocol.

The European Low-Grade Glioma network indicated a need to better understand common practices regarding the managing of diffuse low-grade gliomas. This area has experienced great advances in recent years.

Concomitant Primary CNS Lymphoma and FSH-Pituitary Adenoma Arising Within the Sella. Entirely Coincidental?

Collision tumors are the simultaneous occurrence of more than one type of neoplasm within an anatomic space. In the pituitary sella, collision tumors are exceedingly rare, and not much is known about their etiology and prognosis.

Improved long-term survival with subdural drains following evacuation of chronic subdural haematoma.

Chronic subdural haematoma (CSDH) is a common condition that is effectively managed by burrhole drainage but requires repeat surgery in a significant minority of patients. The Cambridge Chronic Subdural Haematoma Trial (CCSHT) was a randomised controlled study that showed placement of subdural drains for 48 h following burrhole evacuation significantly reduces the incidence of reoperation and improves survival at 6 months. The present study examined the long-term survival of the patients in the trial.

The Effect of 3-Dimensional Simulation on Neurosurgical Skill Acquisition and Surgical Performance: A Review of the Literature.

In recent years, 3-dimensional (3D) simulation of neurosurgical procedures has become increasingly popular as an addition to training programmes. However, there remains little objective evidence of its effectiveness in improving live surgical skill. This review analysed the current literature in 3D neurosurgical simulation, highlighting remaining gaps in the evidence base for improvement in surgical performance and suggests useful future research directions.

Clinical Experience and Results of Microsurgical Resection of Arterioveonous Malformation in the Presence of Space-Occupying Intracerebral Hematoma.

Management of ruptured arteriovenous malformations (AVMs) with a mass-producing intracerebral hematoma (ICH) represents a surgical dilemma.

Volumetric growth rates of meningioma and its correlation with histological diagnosis and clinical outcome: a systematic review.

Tumour growth has been used to successfully predict progression-free survival in low-grade glioma. This systematic review sought to establish the evidence base regarding the correlation of volumetric growth rates with histological diagnosis and potential to predict clinical outcome in patients with meningioma.

Reporting of patient-reported health-related quality of life in adults with diffuse low-grade glioma: a systematic review.

Patient-reported health-related quality of life (HRQoL) analysis can provide important information for managing the balance between treatment benefits and treatment-related adverse effects on quality of life (QoL). This systematic review sought to identify the range of HRQoL measures used for patients with diffuse hemispheric WHO grade II glioma (DLGG) and assess the quality of HRQoL reporting.

Image-guided resection of spheno-orbital skull-base meningiomas with predominant intraosseous component.

Although meningiomas of the spheno-orbital region commonly result in hyperostosis, intraosseous meningiomas, which feature extensive full thickness infiltration of the anterolateral skull base, are rare. In this study, we assess the value of image guidance during surgery for intraosseous spheno-orbital skull-base meningiomas in achieving safe and maximal abnormal bone resection.

Core Outcomes and Common Data Elements in Chronic Subdural Hematoma: A Systematic Review of the Literature Focusing on Baseline and Peri-Operative Care Data Elements.

Chronic subdural hematoma (CSDH) is an increasingly common subtype of head injury, especially in the elderly population. The optimization of treatment strategies has been hampered by the collection of heterogeneous outcome measures and data elements, precluding cross-study comparisons. This study aimed to quantify the heterogeneity of data elements in the pre-operative, operative, and post-operative phases of care, and build the basis for the development of a set of common data elements (CDEs) for CSDH. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered with the PROSPERO register of systematic reviews (CRD42014007266). All full-text English studies with more than 10 patients (prospective) or more than 100 patients (retrospective) published after 1990 examining clinical outcomes in CSDH were eligible for inclusion. One hundred two eligible studies were found. Only 40 studies (39.2%) reported the main presenting symptom/feature and 24 (23.5%) reported additional symptoms/features. Admitting neurological/functional status was classified by the Glasgow Coma Scale (25 studies; 24.5%), the Markwalder Score (26 studies; 25.5%) and the modified Rankin Scale (three studies; 2.9%). Fifty-four studies (52.9%) made some mention of patient comorbidities and 58 studies (56.9%) reported the proportion or excluded patients on anticoagulant medication. Eighteen studies (17.6%) reported baseline coagulation status. Sixty-four studies (62.7%) stratified or assessed severity based on radiological findings, although the methods used varied widely. There was variable reporting of surgical technique and post-operative care; 32 studies (31.4%) made no mention of whether the operations were performed under general or local anesthetic. This study, a part of the Core Outcomes and Common Data Elements in CSDH (CODE-CSDH) project, confirms and quantifies the heterogeneity of data elements collected and reported in CSDH studies to date. It establishes the basis for the consensus-based development of a set of common data elements, facilitating robust cross-study comparisons and resulting improvements in patient outcomes.

Germinoma of the medulla oblongata - A case report.

We describe a case of primary intracranial medulla oblongata germinoma in a 23-year-old female who presented with deteriorating balance and mobility. Imaging demonstrated an exophytic lesion arising from the dorsal medulla oblongata and extending into the fourth ventricle. The tissue sample was obtained via suboccipital craniotomy and a diagnosis of a primary medullary germinoma was made. The patient underwent whole craniospinal axis radiotherapy and remains well and recurrence-free at 1-year follow up.

Core Outcomes and Common Data Elements in Chronic Subdural Hematoma: A Systematic Review of the Literature Focusing on Reported Outcomes.

The plethora of studies in chronic subdural hematoma (CSDH) has not resulted in the development of an evidence-based treatment strategy, largely due to heterogeneous outcome measures that preclude cross-study comparisons and guideline development. This study aimed to identify and quantify the heterogeneity of outcome measures reported in the CSDH literature and to build a case for the development of a consensus-based core outcome set. This systematic review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and was registered with the PROSPERO international prospective register of systematic reviews (CRD42014007266). All full-text English language studies with >10 patients (prospective) or >100 patients (retrospective) published after 1990 examining clinical outcomes in CSDH were eligible for inclusion. One hundred two eligible studies were found. There were 14 (13.7%) randomized controlled trials, one single arm trial (1.0%), 25 (24.5%) cohort comparison studies, and 62 (60.8%) prospective or retrospective cohort studies. Outcome domains reported by the studies included mortality (63.8% of included studies), recurrence (94.1%), complications (48.0%), functional outcomes (40.2%), and radiological (38.2%) outcomes. There was significant heterogeneity in the definitions of the outcome measures, as evidenced by the seven different definitions of the term "recurrence," with no definition given in 19 studies. The time-points of assessment for all the outcome domains varied greatly from inpatient/hospital discharge to 18 months. This study establishes and quantifies the heterogeneity of outcome measure reporting in CSDH and builds the case for the development of a robust consensus-based core outcome set for future studies to adhere to as part of the Core Outcomes and Common Data Elements in CSDH (CODE-CSDH) project.

Origins and functional consequences of somatic mitochondrial DNA mutations in human cancer.

Recent sequencing studies have extensively explored the somatic alterations present in the nuclear genomes of cancers. Although mitochondria control energy metabolism and apoptosis, the origins and impact of cancer-associated mutations in mtDNA are unclear. In this study, we analyzed somatic alterations in mtDNA from 1675 tumors. We identified 1907 somatic substitutions, which exhibited dramatic replicative strand bias, predominantly C > T and A > G on the mitochondrial heavy strand. This strand-asymmetric signature differs from those found in nuclear cancer genomes but matches the inferred germline process shaping primate mtDNA sequence content. A number of mtDNA mutations showed considerable heterogeneity across tumor types. Missense mutations were selectively neutral and often gradually drifted towards homoplasmy over time. In contrast, mutations resulting in protein truncation undergo negative selection and were almost exclusively heteroplasmic. Our findings indicate that the endogenous mutational mechanism has far greater impact than any other external mutagens in mitochondria and is fundamentally linked to mtDNA replication.

Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey.

Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children.

Chronic subdural haematoma: modern management and emerging therapies.

Chronic subdural haematoma (CSDH) is one of the most common neurological disorders, and is especially prevalent among elderly individuals. Surgical evacuation is the mainstay of management for symptomatic patients or haematomas exerting significant mass effect. Although burr hole craniostomy is the most widely practised technique worldwide, approximately 10-20% of surgically treated patients experience postoperative recurrence necessitating reoperation. Given the increasing incidence of CSDH in a growing elderly population, a need exists for refined techniques that combine a minimally invasive approach with clinical efficacy and cost-effectiveness. In addition, nonsurgical treatment modalities, such as steroids, are attracting considerable interest, as they have the potential to reduce postoperative recurrence or even replace the need for surgery in selected patients. This Review provides an overview of the contemporary management of CSDH and presents considerations regarding future approaches that could further optimize patient care and outcomes.

Alternative cost-effective method to record 3D intra-operative images: a technical note.

The educational value of stereoscopic imaging in neurosurgical training has increasingly been appreciated and its use increased during the last decade. We describe a technique that we developed to acquire and reproduce intra-operative stereoscopic images.

Current concepts in the surgical management of glioma patients.

The scientific basis for the surgical management of patients with glioma is rapidly evolving. The infiltrative nature of these cancers precludes a surgical cure, but despite this, cytoreductive surgery remains central to high-quality patient care. In addition to tissue sampling for accurate histopathological diagnosis and molecular genetic characterisation, clinical benefit from decompression of space-occupying lesions and microsurgical cytoreduction has been reported in patients with different grades of glioma. By integrating advanced surgical techniques with molecular genetic characterisation of the disease and targeted radiotherapy and chemotherapy, it is possible to construct a programme of personalised surgical therapy throughout the patient journey. The goal of therapeutic packages tailored to each patient is to optimise patient safety and clinical outcome and must be delivered in a multidisciplinary setting. Here we review the current concepts that underlie surgical subspecialisation in the management of patients with glioma.

Twist-drill craniostomy with hollow screws for evacuation of chronic subdural hematoma.

OBJECT.: The incidence of chronic subdural hematoma (CSDH) is expected to increase substantially over the next 25 years. Continuing refinement of techniques for surgical evacuation is essential for optimizing patient outcomes. A novel technique involving a hollow screw, which is threaded through a twist-drill hole in the cranium and then connected to a closed drainage system, has been increasing in popularity. The aim of this systematic review is to collate and analyze the published experience with this novel technique and to evaluate its efficacy in comparison with the other surgical treatment methods.

Processed pseudogenes acquired somatically during cancer development.

Cancer evolves by mutation, with somatic reactivation of retrotransposons being one such mutational process. Germline retrotransposition can cause processed pseudogenes, but whether this occurs somatically has not been evaluated. Here we screen sequencing data from 660 cancer samples for somatically acquired pseudogenes. We find 42 events in 17 samples, especially non-small cell lung cancer (5/27) and colorectal cancer (2/11). Genomic features mirror those of germline LINE element retrotranspositions, with frequent target-site duplications (67%), consensus TTTTAA sites at insertion points, inverted rearrangements (21%), 5' truncation (74%) and polyA tails (88%). Transcriptional consequences include expression of pseudogenes from UTRs or introns of target genes. In addition, a somatic pseudogene that integrated into the promoter and first exon of the tumour suppressor gene, MGA, abrogated expression from that allele. Thus, formation of processed pseudogenes represents a new class of mutation occurring during cancer development, with potentially diverse functional consequences depending on genomic context.

Delayed neurological deficit following resection of tuberculum sellae meningioma: report of two cases, one with permanent and one with reversible visual impairment.

The most common presentation of patients with tuberculum sellae meningiomas is visual loss, and surgical resection is the main mode of treatment. Preservation of vision is not only the main objective of the surgery; loss of vision is also its main risk. Visual deterioration following surgery is usually apparent immediately post-operatively. Here we present two cases of patients who underwent resection of tuberculum sellae meningioma and whose vision following surgery was initially unchanged until the postoperative day two when dramatic visual deterioration occurred. In the first case this resulted in blindness, whereas in the second case vision recovered back to the preoperative state. The possible mechanisms of visual deterioration and modes of treatment are discussed.

Giant intracranial hemangioma in a neonate.

In this report we detail the case of an infant presenting with a giant intracranial congenital hemangioma and describe the clinical features and surgical management. Congenital hemangiomas are benign vascular tumors that typically present as skin lesions in neonates and infants. On rare occasions they present as intracranial tumors. The possibility that these tumors may undergo spontaneous regression poses a treatment dilemma.

Diffuse cerebral vasospasm following resection of a hypoglossal schwannoma in a child.

Diffuse cerebral vasospasm is a rare complication following tumour resection. This phenomenon seems to be even rarer in the paediatric population and more so following resections of posterior fossa tumours. Here we report diffuse cerebral vasospasm in a child with hypoglossal nerve Schwannoma eight days following resection of the tumour.

Community consultation in emergency neurosurgical research: lessons from a proposed trial for patients with chronic subdural haematomas.

Chronic subdural haematoma (CSDH) is one of the most common neurosurgical disorders and is especially prevalent in old age. The subdural evacuating port system (SEPS) has emerged in the last few years as a minimally invasive alternative to the standard procedure of burr-hole evacuation. NHS practice is evidence-driven and evidence from high-quality clinical studies is required prior to implementation of any changes. In the UK, the National Research Ethics Service (NRES) advises community consultation prior to starting a clinical trial, where the patient is unlikely to have capacity to consent to enrolment in the trial. To prepare for a trial comparing minimally invasive (SEPS) versus burr-hole evacuation for evacuation of a CSDH, we have designed and undertaken a pre-protocol community consultation survey to examine potential patient participation. MATERIAL(S) AND METHODS: The study population consisted of patients, family members and carers/friends in neurosurgical clinic waiting rooms and wards at Addenbrooke's Hospital, Cambridge, who individually completed a questionnaire (n = 215).

Muscle and nerve biopsy for the neurosurgical trainee.

Nerve and muscle biopsy are common procedures often performed by junior surgical trainees. This educational review article describes the operative details of performing biopsies of muscle and nerve. Indications, pre-operative investigations and complication rates are described to aid in proper patient selection.

Ophthalmological outcome after resection of tumors based on the pineal gland.

Descriptions of visual dysfunction in pineal gland tumors tend to focus on upward gaze palsy alone. The authors aimed to characterize the nature, incidence, and functional significance of ophthalmological dysfunction after resection of tumors based on the pineal gland.

Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations.

Meningiomas are among the most frequent intracranial tumors. The secretory variant of meningioma is characterized by glandular differentiation, formation of intracellular lumina and pseudopsammoma bodies, expression of a distinct pattern of cytokeratins and clinically by pronounced perifocal brain edema. Here we describe whole-exome sequencing analysis of DNA from 16 secretory meningiomas and corresponding constitutional tissues. All secretory meningiomas invariably harbored a mutation in both KLF4 and TRAF7. Validation in an independent cohort of 14 secretory meningiomas by Sanger sequencing or derived cleaved amplified polymorphic sequence (dCAPS) assay detected the same pattern, with KLF4 mutations observed in a total of 30/30 and TRAF7 mutations in 29/30 of these tumors. All KLF4 mutations were identical, affected codon 409 and resulted in a lysine to glutamine exchange (K409Q). KLF4 mutations were not found in 89 non-secretory meningiomas, 267 other intracranial tumors including gliomas, glioneuronal tumors, pituitary adenomas and metastases, 59 peripheral nerve sheath tumors and 52 pancreatic tumors. TRAF7 mutations were restricted to the WD40 domains. While KLF4 mutations were exclusively seen in secretory meningiomas, TRAF7 mutations were also observed in 7/89 (8 %) of non-secretory meningiomas. KLF4 and TRAF7 mutations were mutually exclusive with NF2 mutations. In conclusion, our findings suggest an essential contribution of combined KLF4 K409Q and TRAF7 mutations in the genesis of secretory meningioma and demonstrate a role for TRAF7 alterations in other non-NF2 meningiomas.

Role of surgery, radiotherapy and chemotherapy in papillary tumors of the pineal region: a multicenter study.

Papillary tumor of the pineal region (PTPR), recently described as a distinct clinicopathological entity, can show aggressive biological behavior. The optimal therapeutic approach of PTPR has not been well defined. The role of surgery, radiotherapy, and chemotherapy in the treatment of PTPR was analyzed in a large multicenter series. In order to determine factors that influence prognosis, outcome data of a series of 44 patients with histopathologically proven PTPR were retrospectively analyzed. Of the 44 patients, 32 were still alive after a median follow-up of 63.1 months. Twelve patients experienced progressive disease, with seven undergoing two relapses and five more than two. Median overall survival (OS) was not achieved. Median progression-free survival (PFS) was 58.1 months. Only gross total resection and younger age were associated with a longer OS, radiotherapy and chemotherapy having no significant impact. PFS was not influenced by gross total resection. Radiotherapy and chemotherapy had no significant effect. This retrospective series confirms the high risk of recurrence in PTPR and emphasizes the importance of gross total resection. However, our data provide no evidence for a role of adjuvant radiotherapy or chemotherapy in the treatment of PTPR.

How I do it--pineal surgery: supracerebellar infratentorial versus occipital transtentorial.

Resection of a pineal tumour requires fastidious pre-operative planning to select the optimal surgical approach and maximise resection while minimising morbidity.

Isolated hypoglossal schwannoma in a 9-year-old child.

The authors report a case of an isolated schwannoma of left hypoglossal nerve in a 9-year-old girl. To the authors' knowledge, this is the first case report of hypoglossal nerve schwannoma in the pediatric population in the absence of neurofibromatosis Type 2. The patient presented with a 2-month history of morning nausea and vomiting with occasional daytime headaches. Magnetic resonance imaging and subsequent CT scanning revealed a dumbbell tumor with a belly in the lower third of the posterior fossa and head underneath the left jugular foramen. Its neck protruded through an expanded hypoglossal canal. Although the lesion bore radiological characteristics of a hypoglossal schwannoma, the absence of hypoglossal palsy and the apparent lack of such tumors in the pediatric population the preoperative diagnosis was not certain. The tumor was approached via a midline suboccipital craniotomy, and gross-total resection was achieved. Pathological examination confirmed the diagnosis of schwannoma. Blood and tumor tests for mutations in the NF2 gene were negative. Postoperative mild hypoglossal palsy recovered by the 3-month follow-up, and an MRI study obtained at 1 year did not show recurrence.

Transient perioperative brainstem paralysis secondary to a local anesthetic.

Local anesthesia is widely used, in isolation or in conjunction with general anesthesia. The authors describe 2 adolescent patients presenting with absent brainstem reflexes and delayed awakening following elective foramen magnum decompression for Chiari Type I malformation. In both cases, neurological deficits were closely associated with the administration of a levobupivacaine field block following wound closure. In the absence of any structural or biochemical abnormalities, and with spontaneous recovery approximating the anesthetic half-life, the authors' observations are consistent with transient brainstem paralysis caused by perioperative local anesthetic infiltration.

Decompressive craniectomy - operative technique and perioperative care.

With improvements in neurocritical care advanced measures of treating raised intracranial pressure (ICP) are more frequently utilised. Decompressive craniectomy is an effective ICP-lowering procedure; however its benefits are maximised with optimal surgical technique and perioperative care, as well as by paying attention to possible complications. This article focuses on the current indications and rationale for decompressive craniectomy, and the surgical technique of bifrontal and unilateral decompression. The key surgical points include a large craniectomy window and opening of the dura, leaving it unsutured or performing a wide non-constricting duroplasty. Perioperative care and possible complications are also discussed.

A census of amplified and overexpressed human cancer genes.

Integrated genome-wide screens of DNA copy number and gene expression in human cancers have accelerated the rate of discovery of amplified and overexpressed genes. However, the biological importance of most of the genes identified in such studies remains unclear. In this Analysis, we propose a weight-of-evidence based classification system for identifying individual genes in amplified regions that are selected for during tumour development. In a census of the published literature we have identified 77 genes for which there is good evidence of involvement in the development of human cancer.

Working toward rational and evidence-based treatment of chronic subdural hematoma.

Chronic subdural hematoma (CSDH) is one of the most common neurosurgical conditions that can usually be treated with relatively simple and effective surgical procedures. It affects primarily the elderly, a rising population worldwide. Together with improved awareness among the medical profession and greater access to modern imaging facilities, the incidence of CSDH is set to rise significantly. Maximization of the efficiency of management of CSDH is therefore a priority. To this end, a review of the findings of clinical and laboratory research underpinning the basis of the modern management of CSDH has been carried out. This review focuses on the pathophysiology and briefly discusses the epidemiology, clinical presentation, and surgical treatments of CSDH, concluding that a one-for-all management strategy is not appropriate. Creating rational bases for the selection of an ideal treatment strategy for an individual patient should be the target. This can be achieved through better understanding of the nature of the condition through systematic basic science research, ascertaining the merits of different surgical techniques in well-designed and rigorously executed clinical trials, using advances in imaging techniques to classify CSDH (a subject not addressed here), and training in and ongoing refinement of clinical acumen and surgical skills of individual surgeons.

Clinical assessment of cerebrospinal fluid dynamics in hydrocephalus. Guide to interpretation based on observational study.

The term hydrocephalus encompasses a range of disorders characterised by clinical symptoms, abnormal brain imaging and derangement of cerebrospinal fluid (CSF) dynamics. The ability to elucidate which patients would benefit from CSF diversion (a shunt or third ventriculostomy) is often unclear. Similar difficulties are often encountered in shunted patients to predict the scope for improvement by shunt re-adjustment or revision. In this study we aimed to update our knowledge of how key quantitative parameters describing CSF dynamics may be used in diagnosis of shunt-responsive hydrocephalus and in the assessment of shunt function.

Causes of neurological deficits following clipping of 200 consecutive ruptured aneurysms in patients with good-grade aneurysmal subarachnoid haemorrhage.

The surgical risk of unruptured aneurysms is well quantified. Although the outcomes for ruptured aneurysms are also well described, due to the concurrent morbidity from the natural history of the haemorrhage, the relative contributions of surgery and natural history to outcome following aneurysmal subarachnoid haemorrhage (SAH) is not. Our aim was to quantify these risks.

The role of external drains and peritoneal conduits in the treatment of recurrent chronic subdural hematoma.

A considerable body of evidence supporting the use of external drainage after evacuation of primary chronic subdural hematoma (CSDH) exists in the literature. However, no systematic study of the value of postoperative drainage in the treatment of recurrent CSDH has been published. The aim of the study was to investigate external drains and subdural-to-peritoneal conduit in the treatment of recurrent CSDH.

Impact of duration of symptoms on CSF dynamics in idiopathic normal pressure hydrocephalus.

Cerebrospinal fluid (CSF) pressure-volume compensation may change over time as part of normal ageing, where the resistance to CSF outflow increases and the formation of CSF decreases with age. Is CSF compensation dependent on duration of symptoms in idiopathic normal pressure hydrocephalus (iNPH)?

GLO1-A novel amplified gene in human cancer.

To identify a novel amplified cancer gene a systematic screen of 975 human cancer DNA samples, 750 cell lines and 225 primary tumors, using the Affymetrix 10K SNP microarray was undertaken. The screen identified 193 amplicons. A previously uncharacterized amplicon located on 6p21.2 whose 1 Mb minimal common amplified region contained eight genes (GLO1, DNAH8, GLP1R, C6orf64, KCNK5, KCNK17, KCNK16, and C6orf102) was further investigated to determine which gene(s) are the biological targets of this amplicon. Real time quantitative PCR (qPCR) analysis of all amplicon 6p21.2 genes in 618 human cancer cell lines identified GLO1, encoding glyoxalase 1, to be the most frequently amplified gene [twofold or greater amplification in 8.4% (49/536) of cancers]. Also the association between amplification and overexpression was greatest for GLO1. RNAi knockdown of GLO1 had the greatest and most consistent impact on cell accumulation and apoptosis. Cell lines with GLO1 amplification were more sensitive to inhibition of GLO1 by bromobenzylglutathione cyclopentyl diester (BBGC). Subsequent qPCR of 520 primary tumor samples identified twofold and greater amplification of GLO1 in 8/37 (22%) of breast, 12/71 (17%) of sarcomas, 6/53 (11.3%) of nonsmall cell lung, 2/23 (8.7%) of bladder, 6/93 (6.5%) of renal and 5/83 (6%) of gastric cancers. Amplification of GLO1 was rare in colon cancer (1/35) and glioma (1/94). Collectively the results indicate that GLO1 is at least one of the targets of gene amplification on 6p21.2 and may represent a useful target for therapy in cancers with GLO1 amplification.

Imidazopurinones are markers of physiological genomic damage linked to DNA instability and glyoxalase 1-associated tumour multidrug resistance.

Glyoxal and methylglyoxal are reactive dicarbonyl metabolites formed and metabolized in physiological systems. Increased exposure to these dicarbonyls is linked to mutagenesis and cytotoxicity and enhanced dicarbonyl metabolism by overexpression of glyoxalase 1 is linked to tumour multidrug resistance in cancer chemotherapy. We report herein that glycation of DNA by glyoxal and methylglyoxal produces a quantitatively important class of nucleotide adduct in physiological systems-imidazopurinones. The adduct derived from methylglyoxal-3-(2'-deoxyribosyl)-6,7-dihydro-6,7-dihydroxy-6/7-methylimidazo-[2,3-b]purine-9(8)one isomers-was the major quantitative adduct detected in mononuclear leukocytes in vivo and tumour cell lines in vitro. It was linked to frequency of DNA strand breaks and increased markedly during apoptosis induced by a cell permeable glyoxalase 1 inhibitor. Unexpectedly, the DNA content of methylglyoxal-derived imidazopurinone and oxidative marker 7,8-dihydro-8-oxo-2'-deoxyguanosine were increased moderately in glyoxalase 1-linked multidrug resistant tumour cell lines. Together these findings suggest that imidazopurinones are a major type of endogenous DNA damage and glyoxalase 1 overexpression in tumour cells strives to counter increased imidazopurinone formation in tumour cells likely linked to their high glycolytic activity.

PICNIC: an algorithm to predict absolute allelic copy number variation with microarray cancer data.

High-throughput oligonucleotide microarrays are commonly employed to investigate genetic disease, including cancer. The algorithms employed to extract genotypes and copy number variation function optimally for diploid genomes usually associated with inherited disease. However, cancer genomes are aneuploid in nature leading to systematic errors when using these techniques. We introduce a preprocessing transformation and hidden Markov model algorithm bespoke to cancer. This produces genotype classification, specification of regions of loss of heterozygosity, and absolute allelic copy number segmentation. Accurate prediction is demonstrated with a combination of independent experimental techniques. These methods are exemplified with affymetrix genome-wide SNP6.0 data from 755 cancer cell lines, enabling inference upon a number of features of biological interest. These data and the coded algorithm are freely available for download.

Use of drains versus no drains after burr-hole evacuation of chronic subdural haematoma: a randomised controlled trial.

Chronic subdural haematoma causes serious morbidity and mortality. It recurs after surgical evacuation in 5-30% of patients. Drains might reduce recurrence but are not used routinely. Our aim was to investigate the effect of drains on recurrence rates and clinical outcomes.

What constitutes Clinical Equipoise?

In order to incorporate patients ethically into randomised clinical trials, two related but distinct concepts are used: 'Clinical Equipoise' and the 'Uncertainty Principle'. We argue that true 'Clinical Equipoise', a consensus of opinion regarding valid treatment options, is a more valid way of recruiting to neurosurgical randomised clinical trials than the 'Uncertainty Principle', which reflects an individual clinician's uncertainty. This subtle distinction has implications for both recruitment and interpretation of the results of randomised clinical trials.

Arteriovenous malformations.

Arteriovenous malformations (AVMs) represent one of the most complex lesions encountered by the vascular neurosurgeon. They are thought to arise by a developmental aberration early in fetal life leading to structurally abnormal vessels, characterised by arteriovenous shunting. AVMs may present in a number of ways, the most devastating being hemorrhage. Their natural history, particularly hemorrhage risk, has been extensively studied and is crucial in informing management decisions. The primary goal of treatment is to eliminate hemorrhage risk. Success in treating these lesions involves comprehensive evaluation of the lesions to balance the risk of haemorrhage against the risk of treatment. Thus, first the decision whether to treat is made followed by selecting the optimum modality of treatment. Successful surgical treatment of AVMs requires extensive preoperative planning and meticulous microsurgical technique.

Paraganglioma of cauda equina.

The clinical, radiological and pathological features of a paraganglioma resulting in cauda equina syndrome are described, including magnetic resonance imaging features. The literature is reviewed and discussed.

Radiotherapy as an adjuvant in the management of intracranial meningiomas: are we practising evidence-based medicine?

Although increasingly used, the precise role of radiotherapy in the management of meningiomas is still disputed. The objective of this study, therefore, was to appraise the evidence for adjuvant radiotherapy in benign and atypical intracranial meningiomas, and to compare and contrast it with the current opinion and practice of neurosurgeons in the United Kingdom and the Republic of Ireland. The use of radiotherapy as a primary treatment strategy or its use in the treatment of recurrence was not considered. We performed a systematic review of the evidence for adjuvant radiotherapy in benign and atypical intracranial meningiomas, surveyed current opinion amongst neurosurgeons involved in such cases and ascertained local practice using data from the regional cancer registry. Overall, 10 cohorts were identified that fulfilled our eligibility criteria. Four studies showed significantly improved local control in patients receiving adjuvant radiotherapy for incompletely resected grade I meningiomas. Our survey demonstrated that the vast majority (98%) of neurosurgeons would not recommend adjuvant radiotherapy in grade I meningioma. In grade II meningioma, most (80%) would not advocate adjuvant radiotherapy if completely excised, but the majority (59%) would recommend radiotherapy in cases of subtotal resection. Significant variation in opinion between centres exists, however, particularly in cases of completely resected atypical meningiomas (p = 0.02). Data from the Eastern Cancer Registration and Information Centre appears to be in line with these findings: less than 10% of patients with grade I meningiomas, but almost 30% of patients with grade II meningiomas received adjuvant radiotherapy in the Eastern region. In conclusion, our study has highlighted significant variation in opinion and practice, reflecting a lack of class 1 evidence to support the use of adjuvant radiotherapy in the treatment of meningiomas. Efforts are underway to address this with a randomized multicentre trial comparing a policy of watchful waiting versus adjuvant irradiation.

The management of primary chronic subdural haematoma: a questionnaire survey of practice in the United Kingdom and the Republic of Ireland.

A wide range of treatment modalities are employed in the treatment of chronic subdural haematoma (CSDH). A rational and evidence-based treatment strategy has the potential to optimise treatment for the individual patient and save resources. The aim of this study was to survey aspects of current practice in the UK and Ireland. A 1-page postal questionnaire addressing the treatment of primary (i.e. not recurrent) CSDH was sent to consultant SBNS members in March 2006. There were 112 responses from 215 questionnaires (52%). The preferred surgical technique was burr hole drainage (92%). Most surgeons prefer not to place a drain, with 27% never using one and 58% using drain only in one-quarter of cases or less. Only 11% of surgeons always place a drain, and only 30% place one in 75% of cases or more. The closed subdural-to-external drainage was most commonly used (91%) with closed subgaleal-to-external and subdural-to-peritoneal conduit used less often (3 and 4%, respectively). Only 5% of responders claimed to know the exact recurrence rate. The average perceived recurrence rate among the surgeons that never use drains and those who always use drains, was the same (both 11%). Most operations are performed by registrars (77%). Postoperative imaging is requested routinely by 32% of respondents and 57% of surgeons prescribe bed rest. Ninety four per cent surgeons employ conservative management in less than one-quarter of cases. Forty-two per cent of surgeons never prescribe steroids, 55% prescribe them to those managed conservatively. This survey demonstrates that there are diverse practices in the management of CSDH. This may be because of sufficiently persuasive evidence either does not exist or is not always taken into account. The current literature provides Class II and III evidence and there is a need for randomized studies to address the role of external drainage, steroids and postoperative bed rest.

Survey on current cognitive practices within the European Low-Grade Glioma Network: towards a European assessment protocol.

The European Low-Grade Glioma network indicated a need to better understand common practices regarding the managing of diffuse low-grade gliomas. This area has experienced great advances in recent years.

Concomitant Primary CNS Lymphoma and FSH-Pituitary Adenoma Arising Within the Sella. Entirely Coincidental?

Collision tumors are the simultaneous occurrence of more than one type of neoplasm within an anatomic space. In the pituitary sella, collision tumors are exceedingly rare, and not much is known about their etiology and prognosis.

Reporting of patient-reported health-related quality of life in adults with diffuse low-grade glioma: a systematic review.

Patient-reported health-related quality of life (HRQoL) analysis can provide important information for managing the balance between treatment benefits and treatment-related adverse effects on quality of life (QoL). This systematic review sought to identify the range of HRQoL measures used for patients with diffuse hemispheric WHO grade II glioma (DLGG) and assess the quality of HRQoL reporting.

Germinoma of the medulla oblongata - A case report.

We describe a case of primary intracranial medulla oblongata germinoma in a 23-year-old female who presented with deteriorating balance and mobility. Imaging demonstrated an exophytic lesion arising from the dorsal medulla oblongata and extending into the fourth ventricle. The tissue sample was obtained via suboccipital craniotomy and a diagnosis of a primary medullary germinoma was made. The patient underwent whole craniospinal axis radiotherapy and remains well and recurrence-free at 1-year follow up.

Predicting the "usefulness" of 5-ALA-derived tumor fluorescence for fluorescence-guided resections in pediatric brain tumors: a European survey.

Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. Case reports indicate that 5-ALA can be used for children, yet no prospective study has been conducted as of yet. As a basis for a study, we conducted a survey among certified European Gliolan users to collect data on their experiences with children.

Current concepts in the surgical management of glioma patients.

The scientific basis for the surgical management of patients with glioma is rapidly evolving. The infiltrative nature of these cancers precludes a surgical cure, but despite this, cytoreductive surgery remains central to high-quality patient care. In addition to tissue sampling for accurate histopathological diagnosis and molecular genetic characterisation, clinical benefit from decompression of space-occupying lesions and microsurgical cytoreduction has been reported in patients with different grades of glioma. By integrating advanced surgical techniques with molecular genetic characterisation of the disease and targeted radiotherapy and chemotherapy, it is possible to construct a programme of personalised surgical therapy throughout the patient journey. The goal of therapeutic packages tailored to each patient is to optimise patient safety and clinical outcome and must be delivered in a multidisciplinary setting. Here we review the current concepts that underlie surgical subspecialisation in the management of patients with glioma.

Giant intracranial hemangioma in a neonate.

In this report we detail the case of an infant presenting with a giant intracranial congenital hemangioma and describe the clinical features and surgical management. Congenital hemangiomas are benign vascular tumors that typically present as skin lesions in neonates and infants. On rare occasions they present as intracranial tumors. The possibility that these tumors may undergo spontaneous regression poses a treatment dilemma.

Ophthalmological outcome after resection of tumors based on the pineal gland.

Descriptions of visual dysfunction in pineal gland tumors tend to focus on upward gaze palsy alone. The authors aimed to characterize the nature, incidence, and functional significance of ophthalmological dysfunction after resection of tumors based on the pineal gland.

Role of surgery, radiotherapy and chemotherapy in papillary tumors of the pineal region: a multicenter study.

Papillary tumor of the pineal region (PTPR), recently described as a distinct clinicopathological entity, can show aggressive biological behavior. The optimal therapeutic approach of PTPR has not been well defined. The role of surgery, radiotherapy, and chemotherapy in the treatment of PTPR was analyzed in a large multicenter series. In order to determine factors that influence prognosis, outcome data of a series of 44 patients with histopathologically proven PTPR were retrospectively analyzed. Of the 44 patients, 32 were still alive after a median follow-up of 63.1 months. Twelve patients experienced progressive disease, with seven undergoing two relapses and five more than two. Median overall survival (OS) was not achieved. Median progression-free survival (PFS) was 58.1 months. Only gross total resection and younger age were associated with a longer OS, radiotherapy and chemotherapy having no significant impact. PFS was not influenced by gross total resection. Radiotherapy and chemotherapy had no significant effect. This retrospective series confirms the high risk of recurrence in PTPR and emphasizes the importance of gross total resection. However, our data provide no evidence for a role of adjuvant radiotherapy or chemotherapy in the treatment of PTPR.

How I do it--pineal surgery: supracerebellar infratentorial versus occipital transtentorial.

Resection of a pineal tumour requires fastidious pre-operative planning to select the optimal surgical approach and maximise resection while minimising morbidity.

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