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To formulate Functional Assessment of Cancer Therapy-Meningioma (FACT-MNG), a web-based tumor site-specific outcome instrument for assessing intracranial meningioma patients following surgical resection or stereotactic radiosurgery. We surveyed the relevant literature available on intracranial meningioma surgery and subsequent outcomes (38 papers), making note of which, if any, QOL/outcome instruments were utilized. None of the surgveyed papers included QOL assessment specific to tumor site. We subsequently developed questions that were relevant to the signs and symptoms that characterize each of 11 intracranial meningioma sites, and incorporated them into a modified combination of the Functional Assessment of Cancer Therapy-Brain (FACT-BR) and SF36 outcome instruments, thereby creating a new tumor site-specific outcome instrument, FACT-MNG. With outcomes analysis of surgical and radiosurgical treatments becoming more important, measures of the adequacy and success of treatment are needed. FACT-MNG represents a first effort to formalize such an instrument for meningioma patients. Questions specific to tumor site will allow surgeons to better assess specific quality of life issues not addressed in the past by more general questionnaires.

Epilepsy, a recurrent seizure disorder affecting 1% of the population, can be genetic in origin and thereby affect multiple members in a family, or it can be sporadic. Many sporadic seizures come from a specific "focus" in the cortex. Focal-onset seizures account for 60% of all cases of epilepsy. Among patients with partial seizures, 35% respond poorly to available medication and may benefit from neurosurgical excisional surgery. In cases in which epilepsy is localized through different modes (electroencephalogram, magnetic resonance imaging, etc) to a specific area of the brain where there is an associated lesion, more than half of patients can expect a successful surgical outcome. In patients with consistent seizure-associated behavior but without a lesion, surgical treatment is less successful. Ms H, a young woman with a history of medically intractable partial epilepsy, does not have an anatomical lesion but wants to know if a surgical approach is a good option for her. [ABSTRACT FROM AUTHOR]

Previous studies have suggested an association of personal hair dye use with bladder and hematopoietic cancers. Risks for brain tumors are not well understood. The authors investigated associations between use of synthetic hair dyes and risk of brain tumors in a hospital-based case-control study. The study included adults newly diagnosed with glioma (n = 489), meningioma (n = 197), or acoustic neuroma (n = 96) between 1994 and 1998 at three urban US hospitals and 799 controls. Odds ratios were estimated and 95% confidence intervals were calculated using unconditional logistic regression. Detailed exposure histories were obtained by interview. There was no consistent pattern of elevated odds ratios for glioma, meningioma, or acoustic neuroma with use or prolonged use of permanent, semipermanent, temporary, or gradual hair dyes. Although use of permanent brown hair dye for 20 or more years was associated with glioma among women, the estimate was imprecise (odds ratio = 3.8, 95% confidence interval: 1.2, 12.5) and was based on just 13 exposed cases; thus, this could be a chance finding. Overall, there was little consistent evidence for an association of synthetic hair dye use with glioma, meningioma, or acoustic neuroma. However, prolonged use of dark-colored permanent dyes warrants further investigation given the high prevalence of hair dyeing. [ABSTRACT FROM AUTHOR]

The enzyme delta-aminolevulinic acid dehydratase (ALAD) , which catalyzes the second step of heme synthesis, can be inhibited by several chemicals, including lead, a potential risk factor for brain tumors, particularly meningioma. In this study we examined whether the ALAD G177C polymorphism in the gene coding for ALAD is associated with risk of intracranial tumors of the brain and nervous system. We use data from a case-control study with 782 incident brain tumor cases and 799 controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to the hospital. Blood samples were drawn and DNA subsequently sent for genotyping for 73% of subjects. ALAD genotype was determined for 94% of these samples (355 glioma, 151 meningioma, 67 acoustic neuroma, and 505 controls) . Having one or more copy of the ALAD2 allele was associated with increased risk for meningioma [odds ratio (OR) = 1.6 ; 95% confidence interval (CI) , 1.0-2.6], with the association appearing stronger in males (OR = 3.5 ; 95% CI, 1.3-9.2) than in females (OR = 1.2 ; 95% CI, 0.7-2.2) . No increased risk associated with the ALAD2 variant was observed for glioma or acoustic neuroma. These findings suggest that the ALAD2 allele may increase genetic susceptibility to meningioma. [ABSTRACT FROM AUTHOR]

Neural stem cells (NSCs) are capable of tremendous migratory potential to areas of pathology in the central nervous system. When implanted into a diseased or injured nervous system, NSCs can travel through great distances to and engraft within areas of discrete as well as diffuse abnormalities. Engraftment is often followed by integration into the local neural milieu, accompanied by stable gene expression from the NSCs. In addition, the pluripotency of NSCs endows them with the capability to replace diseased tissues in an appropriate manner. Recent evidence has also suggested that engrafted exogenous NSCs may have effects on the surrounding microenvironment, such as promoting protection and/or regeneration of host neural pathways. These characteristics of NSCs would seem to make them ideal agents for the treatment of various central nervous system pathologies, especially brain tumors. Brain tumors are generally difficult to treat because of the unique location of the lesions. In primary gliomas, the extensive infiltrative nature of the tumor cells presents a challenge for their effective and total eradication, hence the high rate of treatment failure and disease recurrence. In addition, normal brain structures are distorted and are often destroyed by the growing neoplasm. Even with effective therapy to surgically resect and destroy the neoplastic tissues, the brain is still injured, which often leaves the patient in a debilitated state. The unique ability of NSCs to "home in" on tumor cells followed by the delivery of a desired gene product makes the NSC a very promising agent in brain tumor therapy. Cytolytic viruses and genes coding for anti-tumor cytokines, pro-drug converting enzymes, and various neurotrophic factors have all been engineered into engraftable NSCs for delivery to tumors. When they are specially tagged, such injected NSCs can be visualized with the use of novel imaging techniques and tracked in vivo within living animals over real time. If the NSCs were also capable of participating in the subsequent repair and regeneration of the tumor-afflicted brain-at present a potential but as-yet-unproven aspect of this intervention-then its role in abetting anti-tumor therapy would be complete. It is important to emphasize, however, that the use of NSCs is adjunctive and is not a replacement for other therapies that should be used in parallel. [ABSTRACT FROM AUTHOR]

This paper examines the use of digital endpoints (DEs) derived from digital health technologies (DHTs), focusing primarily on the specific considerations regarding the determination of meaningful change thresholds (MCT). Using DHTs in drug development is becoming more commonplace. There is general acceptance of the value of DHTs supporting patient-centric trial design, capturing data outside the traditional clinical trial setting, and generating DEs with the potential to be more sensitive to change than conventional assessments. However, the transition from exploratory endpoints to primary and secondary endpoints capable of supporting labeling claims requires these endpoints to be substantive with reproducible population-specific values. Meaningful change represents the amount of change in an endpoint measure perceived as important to patients and should be determined for each digital endpoint and given population under consideration. This paper examines existing approaches to determine meaningful change thresholds and explores examples of these methodologies and their use as part of DE development: emphasizing the importance of determining what aspects of health are important to patients and ensuring the DE captures these concepts of interest and aligns with the overarching endpoint strategy. Examples are drawn from published DE qualification documentation and responses to qualification submissions under review by the various regulatory authorities. It is the hope that these insights will inform and strengthen the development and validation of DEs as drug development tools, particularly for those new to the approaches to determine MCTs., (© 2023. The Author(s), under exclusive licence to The Drug Information Association, Inc.)

Overseas, emerging research has shown that where erionite is present in bedrock as a zeolite, and then subsequently disturbed and blown into the atmosphere, resulting exposure is associated with health effects similar to those caused by asbestos, including malignant mesothelioma (MM). Erionite-induced MM is thought to be particularly prevalent in the construction and quarrying industries, in regions where rock containing erionite is disturbed. In 2015, the then Government Chief Scientist, Sir Peter Gluckman, reported that erionite was a more potent carcinogen than asbestos, and more recent studies have established its presence in the Auckland Region. However, globally at present, there are no established occupational exposure limits for erionite, standard sampling and analytical methods or exposure mitigation guidelines. Given the many major construction projects being carried out in Auckland at the present time, which involve the removal of large quantities of bedrock containing erionite, an assessment of the health risks such activities pose to the public is needed., Competing Interests: Nil.

Objectives: Several patient-reported outcome (PRO) instruments have been validated in AS. This study aims to evaluate several measurement properties of such PROs in a broad axial SpA (axSpA) population, including both AS and non-radiographic axSpA (nr-axSpA) subpopulations., Methods: PROs assessed were total and nocturnal back pain, patient global assessment of disease activity, BASDAI, BASFI and the 36-item Short Form Health Survey. A literature review and both clinician and patient qualitative interviews provided information on instrument content validity. Reliability (test-retest and internal consistency), construct validity (PROs, clinical-outcome correlations and known-groups validity) and PRO responsiveness were assessed. Data from the RAPID-axSpA trial (NCT01087762) investigating certolizumab pegol efficacy in axSpA, including relevant subpopulations, were utilized., Results: Concepts identified for the broad axSpA population by both clinician and patient interviews were consistent with those identified through literature review of AS. All PROs demonstrated reliability in the RAPID-axSpA population (n = 325), with test-retest intraclass correlation coefficients and internal consistency Cronbach's α >0.8. Validity was supported by agreement between PROs and clinician-rated measures; except for the 36-item Short Form Health Survey Mental Components Summary, correlations between PROs and physician global assessment of disease activity ranged from 0.28 to 0.42 for week 0 and from 0.53 to 0.65 for week 24. PRO measures showed good sensitivity to change (effect size >0.8) at weeks 12 and 24 for responders. No variations in measurement properties were noted between the subpopulations., Conclusion: This study indicates that both content validity and measurement properties of PRO instruments utilized in AS are preserved in the broad axSpA population., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Dysregulation of ribosome biogenesis or translation can promote cancer, but the underlying mechanisms remain unclear. UTP18 is a component of the small subunit processome, a nucleolar multi-protein complex whose only known function is to cleave pre-ribosomal RNA to yield the 18S ribosomal RNA component of 40S ribosomal subunits. Here, we show that UTP18 also alters translation to promote stress resistance and growth, and that UTP18 is frequently gained and overexpressed in cancer. We observed that UTP18 localizes to the cytoplasm in a subset of cells, and that serum withdrawal increases cytoplasmic UTP18 localization. Cytoplasmic UTP18 associates with the translation complex and Hsp90 to upregulate the translation of IRES-containing transcripts such as HIF1a, Myc and VEGF, thereby inducing stress resistance. Hsp90 inhibition decreases cytoplasmic UTP18 and UTP18-induced increases in translation. Importantly, elevated UTP18 expression correlates with increased aggressiveness and decreased survival in numerous cancers. Enforced UTP18 overexpression promotes transformation and tumorigenesis, whereas UTP18 knockdown inhibits these processes. This stress adaptation mechanism is thus co-opted for growth by cancers, and its inhibition may represent a promising new therapeutic target.

Objective: To compare the diagnostic yield and safety profiles of intraoperative magnetic resonance imaging (MRI)-guided needle brain biopsy with 2 traditional brain biopsy methods: frame-based and frameless stereotactic brain biopsy., Methods: A retrospective analysis was performed of 288 consecutive needle brain biopsies in 277 patients undergoing stereotactic brain biopsy with any of the 3 biopsy methods at Brigham and Women's Hospital from 2000-2008. Variables including age, sex, history of radiation and previous surgery, pathology results, complications, and postoperative length of hospital stay were analyzed., Results: Over the course of 8 years, 288 brain biopsies were performed. Of these, 253 (87.8%) biopsies yielded positive diagnostic tissue. Young age (<40 years old) and history of brain radiation or surgery were significant negative predictors for a positive biopsy diagnostic yield. Excluding patients with prior radiation or surgeries, no significant difference in diagnostic yield was detected among the 3 groups, with frame-based biopsies yielding 96.9%, frameless biopsies yielding 91.8%, and intraoperative MRI-guided needle biopsies yielding 89.9% positive diagnostic yield. Serious adverse events occurred 19 biopsies (6.6%). Intraoperative MRI-guided brain biopsies were associated with less serious adverse events and the shortest postoperative hospital stay., Conclusions: Frame-based, frameless stereotactic, and intraoperative MRI-guided brain needle biopsy techniques have comparable diagnostic yield for patients with no prior treatments (either radiation or surgery). Intraoperative MRI-guided brain biopsy is associated with fewer serious adverse events and shorter hospital stay., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Hemispherectomy is a surgical procedure used to treat medically intractable epilepsy in children with severe unilateral cortical disease secondary to acquired brain or congenital lesions. The major surgical approaches for hemispherectomy are anatomic hemispherectomy, traditional functional hemispherectomy, and peri-insular hemispherotomy. We describe the epilepsy outcome, including the need for reoperation, after hemispherectomy in patients with brain malformations or acquired brain lesions who underwent hemispherectomy for refractory epilepsy., Methods: We conducted a retrospective observational study at Children's Hospital Boston. Cases were ascertained from a research database of patients who underwent epilepsy surgery from 1997 to 2011. Data were obtained from electronic medical records and office charts. Outcome after surgery was defined as improvement in seizures (quantity and severity) represented by the Engel classification score measured at last follow-up, with a minimum of 12 months of follow-up. The need for reoperation for completion of hemispheric disconnection. We also examined whether placement of ventriculoperitoneal shunt was required after hemispherectomy was a secondary outcome., Results: We identified 36 patients who underwent hemispherectomy for severe, medically intractable epilepsy. Group 1 (n = 14) had static acquired lesions, and group 2 (n = 22) had malformations of cortical development. Mean age at surgery for group 1 was 9 years (S.D. 5.5) and 2.77 years for group 2 (S.D. 4.01; P < 0.001). The seizure outcome was good in both groups (Engel score I for 25, II for three, III for six, and IV for two patients) and did not differ between the two groups. In group 1, five patients underwent anatomic hemispherectomy (one had prior focal resection), four underwent functional hemispherectomy, and five underwent peri-insular hemispherotomy; none required a second procedure. In group 2, a total of 14 patients had anatomic hemispherectomy (of these, three had had limited prior focal resection), five had functional hemispherectomy, and three had peri-insular hemispherotomy. Among the patients in group 2 who had had functional hemispherectomy, one required reoperation to complete the disconnection and one required peri-insular hemispherotomy because of persistent seizures. In group 1, three patients underwent a ventriculoperitoneal shunt, and from these patients two underwent anatomic hemispherectomy and one had functional hemispherectomy. In group 2, 12 patients had ventriculoperitoneal shunt, and all of them had anatomic hemispherectomy as a first or second procedure., Conclusion: Seizure outcome after hemispherectomy is good in patients with acquired lesions and with developmental malformations. Although the seizure outcome was similar in the three procedures, the complication rate was higher with anatomic hemispherectomy than with the more recent functional hemispherectomy and peri-insular hemispherotomy. The group with cortical malformations generally had surgery at a younger age; two patients with malformations of cortical development who underwent functional hemispherectomy required second surgeries. The need for reoperation in these cases may reflect the anatomic complexity of developmental hemispheric malformations, which may lead to incomplete disconnection., (Copyright © 2014. Published by Elsevier Inc.)

Objective: Postcraniotomy infections have generally been treated by debridement of infected tissues, disposal of the bone flap, and delayed cranioplasty several months later to repair the resulting skull defect. Debridement followed by retention of the bone flap has also been advocated. Here we propose an alternative operative strategy for the treatment of postcraniotomy infections., Methods: Two patients presenting with clinical and radiographic signs and symptoms of postcraniotomy infections were treated by debridement, bone flap disposal, and immediate titanium mesh cranioplasty. The patients were subsequently administered antibiotics, and their clinical courses were followed., Results: The patients treated in this fashion did not have recurrence of their infections during 3-year follow-up periods., Conclusions: Surgical debridement, bone flap disposal, and immediate titanium mesh cranioplasty may be a suitable option for the treatment of postcraniotomy infections. This treatment strategy facilitates the eradication of infectious sources and obviates the risks and costs associated with a second surgical procedure., (Published by Elsevier Inc.)

Hemimegalencephaly (HMG) is a developmental brain disorder characterized by an enlarged, malformed cerebral hemisphere, typically causing epilepsy that requires surgical resection. We studied resected HMG tissue to test whether the condition might reflect somatic mutations affecting genes critical to brain development. We found that two out of eight HMG samples showed trisomy of chromosome 1q, which encompasses many genes, including AKT3, a gene known to regulate brain size. A third case showed a known activating mutation in AKT3 (c.49G→A, creating p.E17K) that was not present in the patient's blood cells. Remarkably, the E17K mutation in AKT3 is exactly paralogous to E17K mutations in AKT1 and AKT2 recently discovered in somatic overgrowth syndromes. We show that AKT3 is the most abundant AKT paralog in the brain during neurogenesis and that phosphorylated AKT is abundant in cortical progenitor cells. Our data suggest that somatic mutations limited to the brain could represent an important cause of complex neurogenetic disease., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Human mesenchymal stromal cells (hMSC) can be used as a drug delivery vehicle for the treatment of GBM. However, tracking the migration and distribution of these transplanted cells is necessary to interpret therapeutic efficacy. We compared three labeling techniques for their ability to track the migration of transplanted hMSC in an orthotopic mouse xenograft model. hMSC were labeled with three different imaging tags (fluorescence, luciferase or ferumoxide) for imaging by fluorescence, bioluminescence or magnetic resonance imaging (MRI), respectively. hMSC were labeled for all imaging modalities without the use of transfection agents. The labeling efficacy of the tags was confirmed, followed by in vitro and in vivo migration assays to track hMSC migration towards U87 glioma cells. Our results confirmed that the labeled hMSC retained their migratory ability in vitro, similar to unlabeled hMSC. In addition, labeled hMSC migrated towards the U87 tumor site, demonstrating their retention of tumor tropism. hMSC tumor tropism was confirmed by all three imaging modalities; however, MRI provides both real time assessment and the high resolution needed for clinical studies. Our findings suggest that ferumoxide labeling of hMSC is feasible, does not alter their migratory ability and allows detection by MRI. Non invasive tracking of transplanted therapeutic hMSC in the brain will allow further development of human cell based therapies.

Objective: The most common neurological symptom of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) is early life refractory epilepsy. As previous studies have shown enhanced excitatory glutamatergic neurotransmission in TSC and FCD brains, we hypothesized that neurons associated with these lesions may also express altered γ-aminobutyric acid (GABA)(A) receptor (GABA(A)R)-mediated inhibition., Methods: Expression of the GABA(A)R subunits α1 and α4, and the Na(+)-K(+)-2Cl(-) (NKCC1) and the K(+)-Cl(-) (KCC2) transporters, in human TSC and FCD type II specimens were analyzed by Western blot and double label immunocytochemistry. GABA(A) R responses in dysplastic neurons from a single case of TSC were measured by perforated patch recording and compared to normal-appearing cortical neurons from a non-TSC epilepsy case., Results: TSC and FCD type IIb lesions demonstrated decreased expression of GABA(A)R α1, and increased NKCC1 and decreased KCC2 levels. In contrast, FCD type IIa lesions showed decreased α4, and increased expression of both NKCC1 and KCC2 transporters. Patch clamp recordings from dysplastic neurons in acute slices from TSC tubers demonstrated excitatory GABA(A)R responses that were significantly attenuated by the NKCC1 inhibitor bumetanide, in contrast to hyperpolarizing GABA(A)R-mediated currents in normal neurons from non-TSC cortical slices., Interpretation: Expression and function of GABA(A)Rs in TSC and FCD type IIb suggest the relative benzodiazepine insensitivity and more excitatory action of GABA compared to FCD type IIa. These factors may contribute to resistance of seizure activity to anticonvulsants that increase GABAergic function, and may justify add-on trials of the NKCC1 inhibitor bumetanide for the treatment of TSC and FCD type IIb-related epilepsy., (Copyright © 2012 American Neurological Association.)

Mutations of the NF2 gene on chromosome 22q are thought to initiate tumorigenesis in nearly 50% of meningiomas, and 22q deletion is the earliest and most frequent large-scale chromosomal abnormality observed in these tumors. In aggressive meningiomas, 22q deletions are generally accompanied by the presence of large-scale segmental abnormalities involving other chromosomes, but the reasons for this association are unknown. We find that large-scale chromosomal alterations accumulate during meningioma progression primarily in tumors harboring 22q deletions, suggesting 22q-associated chromosomal instability. Here we show frequent codeletion of the DNA repair and tumor suppressor gene, CHEK2, in combination with NF2 on chromosome 22q in a majority of aggressive meningiomas. In addition, tumor-specific splicing of CHEK2 in meningioma leads to decreased functional Chk2 protein expression. We show that enforced Chk2 knockdown in meningioma cells decreases DNA repair. Furthermore, Chk2 depletion increases centrosome amplification, thereby promoting chromosomal instability. Taken together, these data indicate that alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas.

Meningioma, the most frequent tumor in the central nervous system, has few recognized risk factors. We explored the role of allergies in a population-based case-control consortium study of meningioma in five geographic areas. We also studied serum levels of a marker of atopic allergy (IgE) in a subset of study participants, a first for a study on meningioma. Participants (N = 1,065) with surgically resected, pathologically confirmed meningioma and controls (N = 634) selected via random-digit dialing were recruited and interviewed. Cases were less likely than controls to report history of physician-diagnosed allergy [odds ratio (OR) = 0.64; 95% confidence interval (95% CI): 0.51-0.80]. Also, cases (N = 295) had lower total serum IgE than controls [N = 192; OR = 0.85, 95% CI: 0.75-0.98 for each unit of Ln(IgE)]. Similar to glioma and cancers at several other sites, meningioma appears to have an inverse relationship with history of allergies and a biomarker of atopic allergy. As some common opposing predisposition or developmental processes for allergy and meningioma may exist, further research into immune processes that can affect the incidence and natural history of meningioma is warranted., (Copyright © 2011 UICC.)

Objective: To determine the complexity and diversity of the neurosurgery certification and recertification process in member societies of the World Federation of Neurosurgical Societies., Material and Methods: A 13-item survey was sent to 88 national and regional societies that are members of the World Federation of Neurosurgical Societies. Variables included in the survey covered a wide range of aspects pertaining to the certification process achieved by cognitive and oral examinations. The data received from 40 responding societies (response rate 45%) were tabulated, and an individual and comparative (global) analysis was performed for all categories, including eligibility and requirements for certification, examination components, use of computer-assisted technology and imaging, performance, validation of foreign degrees, recertification, and maintenance of certification., Results: We present here the global analysis, which is comparative of all participating societies. Although there is high variability in the structure of certification programs worldwide, performance in knowledge-based examinations is similar. Recertification and maintenance of certification are still under development in many societies., Conclusion: With the onset of globalization, we anticipate that efforts will be made in the future to obtain homogeneity in the structure of certification, recertification, and in criteria for international reciprocity of postgraduate neurosurgical training. Peer-Review Article., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: This study sought to compare objectively the complexity and diversity of the certification process in neurological surgery in member societies of the World Federation of Neurosurgical Societies (WFNS) in the African and Middle Eastern regions., Methods: This report centers on two geographic regions: Africa and the Middle East. We provide a subgroup analysis based on the responses provided to the 13-item survey sent in Part I of this study. The data received were analyzed, and three Regional Complexity Scores (RCS) were designed. To compare national board experience, eligibility requirements to access the certification process, and the obligatory nature of the examinations, a RCS-Organizational score was created (RCS-O, 20 points maximum). To analyze the complexity of the examination, a RCS-Components was designed (RCS-C, 20 points maximum). The sum of both is presented in a global RCS (RCS-G). In addition, a descriptive summary of the certification process per responding society is also provided., Results: Based on the data provided by our RCS system, the highest RCS-G was obtained by South Africa (19 of 40 points), followed by Egypt (18 of 40 points), countries of the Gulf Neurosurgical Society (16 of 40 points), and the Neurosurgical Society of East and Central Africa (16 of 40 points)., Conclusions: This grading system allows societies to compare their process of certification within their continental region and worldwide, potentially identifying aspects for further improvement or development., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Few studies have examined the relationship between human leukocyte antigen (HLA) polymorphisms and adult glioma, particularly at class II loci. We evaluated the association between selected HLA class II polymorphisms and adult glioma in a large, hospital-based case-control study, using unconditional logistic regression. DQB1 06 (OR=1.67, 95% CI=1.17-2.39) and DRB1 13 (OR=1.69, 95% CI=1.08-2.64) alleles were associated with an increased risk of glioma, while the DQB1 05 allele showed an inverse association (OR=0.63, 95% CI=0.43-0.93). These results, which were of borderline significance once controlled for the false discovery rate, suggest a potential role for the DQB1 06, DQB1 05, and DRB1 13 alleles in glioma susceptibility., (Copyright © 2010. Published by Elsevier B.V.)

Recent advents in magnetic resonance spectroscopy (MRS) techniques permit subsequent microarray analysis over the entire human transcriptome in the same tissue biopsies. However, extracting information from such immense quantities of data is limited by difficulties in recognizing and evaluating the relevant patterns of apparent gene expression in the context of the existing knowledge of phenotypes by histopathology. Using a quantitative approach derived from a knowledge base of pathology findings, we present a novel methodology used to process genome-wide transcription and MRS data. This methodology was tested to examine metabolite and genome-wide profiles in MRS and RNA in 55 biopsies from human subjects with brain tumors with ~100% certainty. With the guidance of histopathology and clinical outcome, 15 genes with the assistance of 15 MRS metabolites were able to be distinguished by tumor categories and the prediction of survival was better than when either method was used alone. This new method, combining MRS, genomics, statistics and biological content, improves the typing and understanding of the complexity of human brain tumors, and assists in the search for novel tumor biomarkers. It is an important step for novel drug development, it generates testable hypotheses regarding neoplasia and promises to guide human brain tumor therapy provided improved in vivo methods for monitoring response to therapy are developed.

Objective: To objectively compare the complexity and diversity of the certification process in neurological surgery in member societies of the World Federation of Neurosurgical Societies., Methods: This study centers in continental Asia. We provide here an analysis based on the responses provided to a 13-item survey. The data received were analyzed, and three Regional Complexity Scores (RCS) were designed. To compare national board experience, eligibility requirements for access to the certification process, and the obligatory nature of the examinations, an RCS-Organizational score was created (20 points maximum). To analyze the complexity of the examination, an RCS-Components score was designed (20 points maximum). The sum of both is presented in a Global RCS score. Only those countries that responded to the survey and presented nationwide homogeneity in the conduction of neurosurgery examinations could be included within the scoring system. In addition, a descriptive summary of the certification process per responding society is also provided., Results and Conclusion: On the basis of the data provided by our RCS system, the highest global RCS was achieved by South Korea and Malaysia (21/40 points) followed by the joint examination of Singapore and Hong-Kong (FRCS-Ed) (20/40 points), Japan (17/40 points), the Philippines (15/40 points), and Taiwan (13 points). The experience from these leading countries should be of value to all countries within Asia., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Change detection is a critical component in the diagnosis and monitoring of many slowly evolving pathologies., Objective: This article describes a semiautomatic monitoring approach using longitudinal medical images. We test the method on brain scans of patients with meningioma, which experts have found difficult to monitor because the tumor evolution is very slow and may be obscured by artifacts related to image acquisition., Methods: We describe a semiautomatic procedure targeted toward identifying difficult-to-detect changes in brain tumor imaging. The tool combines input from a medical expert with state-of-the-art technology. The software is easy to calibrate and, in less than 5 minutes, returns the total volume of tumor change in mm. We test the method on postgadolinium, T1-weighted magnetic resonance images of 10 patients with meningioma and compare our results with experts' findings. We also perform benchmark testing with synthetic data., Results: Our experiments indicated that experts' visual inspections are not sensitive enough to detect subtle growth. Measurements based on experts' manual segmentations were highly accurate but also labor intensive. The accuracy of our approach was comparable to the experts' results. However, our approach required far less user input and generated more consistent measurements., Conclusion: The sensitivity of experts' visual inspection is often too low to detect subtle growth of meningiomas from longitudinal scans. Measurements based on experts' segmentation are highly accurate but generally too labor intensive for standard clinical settings. We described an alternative metric that provides accurate and robust measurements of subtle tumor changes while requiring a minimal amount of user input.

The diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is still challenging. Alzheimer's disease (AD), along with vascular dementia, the most important differential diagnosis for iNPH, has several potential cerebrospinal fluid (CSF) biomarkers which might help in the selection of patients for shunt treatment. The aim of this study was to compare a battery of CSF biomarkers including well-known AD-related proteins with CSF from patients with suspected iNPH collected from the external lumbar drainage test (ELD). A total of 35 patients with suspected iNPH patients were evaluated with ELD. CSF was collected in the beginning of the test, and the concentrations of total tau, ptau(181), Aβ(42), NFL, TNF-α, TGFβ1, and VEGF were analysed by ELISA. Twenty-six patients had a positive ELD result-that is, their gait symptoms improved; 9 patients had negative ELD. The levels of all analyzed CSF biomarkers were similar between the groups and none of them predicted the ELD result in these patients. Contrary to expectations lumbar CSF TNF-α concentration was low in iNPH patients.

Objective: To objectively compare the complexity and diversity of the certification process in Neurological Surgery in European member societies of the World Federation of Neurosurgical Societies., Materials and Methods: The attention of this study centers on Europe. We provide here a subgroup analysis based on the responses provided to a 13-item survey. The data received were analyzed and three regional complexity scores (RCS) were designed. To compare national board experience as well as eligibility requirements to access the certification process and obligatory nature of the examinations, a RCS Organizational score was created (RCS-O, 20 points maximum). To analyze the complexity of the examination a RCS Components score was designed (RCS-C, 20 points maximum). The sum of both is presented in a Global RCS score (RCS-G). In addition, a descriptive summary of the certification process per responding society is also provided., Results and Conclusions: Based on the data provided by our RCS system, the highest RCS-G was obtained by the United Kingdom (19/40 points) followed by European Association of Neurosurgical Societies, Poland, and Sweden (16/40 points each), Portugal (15/40 points), and Switzerland (14/40 points). The experience from these leading countries should be of value to all countries of the European Union., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Purpose: Despite initial treatment with surgical resection, radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) virtually always recurs. Surgery is sometimes recommended to treat recurrence. In this study, we sought to devise a preoperative scale that predicts survival after surgery for recurrent glioblastoma multiforme., Patients and Methods: The preoperative clinical and radiographic data of 34 patients who underwent re-operation of recurrent GBM tumors were analyzed using Kaplan-Meier survival analysis and Cox proportional hazards regression modeling. The factors associated with decreased postoperative survival (P < .05) were used to devise a prognostic scale which was validated with a separate cohort of 109 patients., Results: The factors associated with poor postoperative survival were: tumor involvement of prespecified eloquent/critical brain regions (P = .021), Karnofsky performance status (KPS) < or = 80 (P = .030), and tumor volume > or = 50 cm(3) (P = .048). An additive scale (range, 0 to 3 points) comprised of these three variables distinguishes patients with good (0 points), intermediate (1 to 2 points), and poor (3 points) postoperative survival (median survival, 10.8, 4.5, and 1.0 months, respectively; P < .001). The scale identified three statistically distinct groups within the validation cohort as well (median survival, 9.2, 6.3, and 1.9 months, respectively; P < .001)., Conclusion: We devised and validated a preoperative scale that identifies patients likely to have poor, intermediate, and good relative outcomes after surgical resection of a recurrent GBM tumor. Application of this simple scale may be useful in counseling patients regarding their treatment options and in designing clinical trials.