Protocol for the development of a multidisciplinary clinical practice guideline for the care of patients with chronic subdural haematoma.

Introduction: A common neurosurgical condition, chronic subdural haematoma (cSDH) typically affects older people with other underlying health conditions. The care of this potentially vulnerable cohort is often, however, fragmented and suboptimal. In other complex conditions, multidisciplinary guidelines have transformed patient experience and outcomes, but no such framework exists for cSDH. This paper outlines a protocol to develop the first comprehensive multidisciplinary guideline from diagnosis to long-term recovery with cSDH. Methods: The project will be guided by a steering group of key stakeholders and professional organisations and will feature patient and public involvement. Multidisciplinary thematic working groups will examine key aspects of care to formulate appropriate, patient-centered research questions, targeted with evidence review using the GRADE framework. The working groups will then formulate draft clinical recommendations to be used in a modified Delphi process to build consensus on guideline contents. Conclusions: We present a protocol for the development of a multidisciplinary guideline to inform the care of patients with a cSDH, developed by cross-disciplinary working groups and arrived at through a consensus-building process, including a modified online Delphi.

FUTURE-GB: functional and ultrasound-guided resection of glioblastoma - a two-stage randomised control trial.

INTRODUCTION: Surgery remains the mainstay for treatment of primary glioblastoma, followed by radiotherapy and chemotherapy. Current standard of care during surgery involves the intraoperative use of image-guidance and 5-aminolevulinic acid (5-ALA). There are multiple other surgical adjuncts available to the neuro-oncology surgeon. However, access to, and usage of these varies widely in UK practice, with limited evidence of their use. The aim of this trial is to investigate whether the addition of diffusion tensor imaging (DTI) and intraoperative ultrasound (iUS) to the standard of care surgery (intraoperative neuronavigation and 5-ALA) impacts on deterioration free survival (DFS). METHODS AND ANALYSIS: This is a two-stage, randomised control trial (RCT) consisting of an initial non-randomised cohort study based on the principles of the IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up) stage-IIb format, followed by a statistically powered randomised trial comparing the addition of DTI and iUS to the standard of care surgery. A total of 357 patients will be recruited for the RCT. The primary outcome is DFS, defined as the time to either 10-point deterioration in health-related quality of life scores from baseline, without subsequent reversal, progressive disease or death. ETHICS AND DISSEMINATION: The trial was registered in the Integrated Research Application System (Ref: 264482) and approved by a UK research and ethics committee (Ref: 20/LO/0840). Results will be published in a peer-reviewed journal. Further dissemination to participants, patient groups and the wider medical community will use a range of approaches to maximise impact. TRIAL REGISTRATION NUMBER: ISRCTN38834571.

Intraoperative ultrasound in brain tumor surgery: A review and implementation guide.

Accurate and reliable intraoperative neuronavigation is crucial for achieving maximal safe resection of brain tumors. Intraoperative MRI (iMRI) has received significant attention as the next step in improving navigation. However, the immense cost and logistical challenge of iMRI precludes implementation in most centers worldwide. In comparison, intraoperative ultrasound (ioUS) is an affordable tool, easily incorporated into existing theatre infrastructure, and operative workflow. Historically, ultrasound has been perceived as difficult to learn and standardize, with poor, artifact-prone image quality. However, ioUS has dramatically evolved over the last decade, with vast improvements in image quality and well-integrated navigation tools. Advanced techniques, such as contrast-enhanced ultrasound (CEUS), have also matured and moved from the research field into actual clinical use. In this review, we provide a comprehensive and pragmatic guide to ioUS. A suggested protocol to facilitate learning ioUS and improve standardization is provided, and an outline of common artifacts and methods to minimize them given. The review also includes an update of advanced techniques and how they can be incorporated into clinical practice.

Acute bilateral serous retinal detachments with spontaneous resolution in a 6-year-old boy.

A healthy 6-year-old boy presented with acute bilateral vision loss, multiple serous retinal detachments between the vascular arcades and a thickened choroid. Spontaneous resolution occurred over several weeks. We hypothesize that the clinical constellation in our patient is suggestive of acute exudative polymorphous vitelliform maculopathy (AEPVM) or might be an atypical presentation of Vogt-Koyanagi-Harada (VKH) disease. We propose that it was caused by an autoimmune-mediated activation of inflammatory cells at the level of the choroid, induced by an unknown trigger.

Improved Prediction of Surgical Resectability in Patients with Glioblastoma using an Artificial Neural Network.

In managing a patient with glioblastoma (GBM), a surgeon must carefully consider whether sufficient tumour can be removed so that the patient can enjoy the benefits of decompression and cytoreduction, without impacting on the patient's neurological status. In a previous study we identified the five most important anatomical features on a pre-operative MRI that are predictive of surgical resectability and used them to develop a simple, objective, and reproducible grading system. The objective of this study was to apply an artificial neural network (ANN) to improve the prediction of surgical resectability in patients with GBM. Prospectively maintained databases were searched to identify adult patients with supratentorial GBM that underwent craniotomy and resection. Performance of the ANN was evaluated against logistic regression and the standard grading system by analysing their Receiver Operator Characteristic (ROC) curves; Area Under Curve (AUC) and accuracy were calculated and compared using Wilcoxon signed rank test with a value of p < 0.05 considered statistically significant. In all, 135 patients were included, of which 33 (24.4%) were found to have complete excision of all contrast-enhancing tumour. The AUC and accuracy were significantly greater using the ANN compared to the standard grading system (0.87 vs. 0.79 and 83% vs. 80% respectively; p < 0.01 in both cases). In conclusion, an ANN allows for the improved prediction of surgical resectability in patients with GBM.

Imaging and Tissue Biomarkers of Choline Metabolism in Diffuse Adult Glioma: 18F-Fluoromethylcholine PET/CT, Magnetic Resonance Spectroscopy, and Choline Kinase α.

The cellular and molecular basis of choline uptake on PET imaging and MRS-visible choline-containing compounds is not well understood. Choline kinase alpha (ChoKα) is an enzyme that phosphorylates choline, an essential step in membrane synthesis. We investigate choline metabolism through 18F-fluoromethylcholine (18F-FMC) PET, MRS, and tissue ChoKα in human glioma. Fourteen patients with a suspected diffuse glioma underwent multimodal 3T MRI and dynamic 18F-FMC PET/CT prior to surgery. Co-registered PET and MRI data were used to target biopsies to regions of high and low choline signal, and immunohistochemistry for ChoKα expression was performed. The 18F-FMC/PET differentiated WHO (World Health Organization) grade IV from grade II and III tumours, whereas MRS differentiated grade III/IV from grade II tumours. Tumoural 18F-FMC/PET uptake was higher than in normal-appearing white matter across all grades and markedly elevated within regions of contrast enhancement. The 18F-FMC/PET correlated weakly with MRS Cho ratios. ChoKα expression on IHC was negative or weak in all but one glioblastoma sample, and did not correlate with tumour grade or imaging choline markers. MRS and 18F-FMC/PET provide complimentary information on glioma choline metabolism. Tracer uptake is, however, potentially confounded by blood-brain barrier permeability. ChoKα overexpression does not appear to be a common feature in diffuse glioma.

Subarachnoid haemorrhage due to intracranial vertebral artery dissection presenting with atypical cauda equina syndrome features: case report.

BACKGROUND: Failing to recognise the signs and symptoms of subarachnoid haemorrhage (SAH) causes diagnostic delay and may result in poorer outcomes. We report a rare case of SAH secondary to a vertebral artery dissection (VAD) that initially presented with cauda equina-like features, followed by symptoms more typical of SAH. CASE PRESENTATION: A 55-year-old man developed severe lower back pain after sudden movement. Over the next 5 days he developed paraesthesiaes in the feet, progressing to the torso gradually, and reported constipation and reduced sensation when passing urine. On day six he developed left facial palsy, and later gradual-onset headache and intermittent confusion. Magnetic resonance imaging of the brain showed diffuse subarachnoid FLAIR hyperintensity, concerning for blood, including a focus of cortical/subcortical high signal in the left superior parietal lobule, which was confirmed by computed tomography. Digital subtraction angiography demonstrated a left VAD with a fusiform aneurysm. CONCLUSION: We present a very rare case of intracranial VAD with SAH initially presenting with spinal symptoms. The majority of subsequent clinical features were consistent with a parietal focus of cortical subarachnoid blood, as observed on neuroimaging.

Objective image analysis of real-time three-dimensional intraoperative ultrasound for intrinsic brain tumour surgery.

BACKGROUND: There is growing evidence that maximal surgical resection of primary intrinsic brain tumours is beneficial, both by improving progression free and overall survival and also by facilitating postoperative chemotherapy and radiotherapy. Hence, there has been an increase in the popularity of real-time intraoperative imaging in brain tumour surgery. The complex theatre arrangements, prohibitive cost and prolonged theatre time of intraoperative MRI have restricted its application. By comparison, intraoperative three-dimensional ultrasound (i3DUS) is user friendly, cost-effective and portable and adds little to surgical time. However, operator-dependent image quality and image interpretation remain limiting factors to the wider application of this technique. The aim of this study was to explore objective i3DUS image analysis and its potential therapeutic role in brain tumour surgery. METHODS: A prospective, observational study was undertaken (approved by the local Research and Ethics Committee prior to recruitment). Biopsies were taken from the solid, necrotic, periphery and brain/tumour interface of intrinsic primary brain tumours. Digital i3DUS images were analysed to extract quantitative parameters from these regions of interest (ROI) in the i3DUS images. These were then correlated with the histology of the relevant specimens. The histopathologist was blinded to the imaging findings. RESULTS: Ninety-seven patients (62 males; mean 54 years) with varying gliomas (84 high grade) were included. Two hundred and ninety regions of interest were analysed. Mean pixel brightness (MPB) and standard deviation (SD) were correlated with histological features. Close correlations were noted between MPB and cellularity, and SD and intrinsic cellular diversity. CONCLUSIONS: MPB and SD are objective measures reflecting the sensitivity of i3DUS in detecting the presence and extent of intrinsic brain tumours. They indirectly suggest heterogeneity, cellularity and invasiveness, providing information of the nature of the tumour, and also reflect the sensitivity of intraoperative US to detect the presence of residual intrinsic brain tumours. Development of this paradigm will enhance i3DUS use as an adjunct in brain tumour surgery. Optimizing its intraoperative application will impact surgical resection and, hence, patient outcome.

Predicting surgical outcome in patients with glioblastoma multiforme using pre-operative magnetic resonance imaging: development and preliminary validation of a grading system.

The lack of a simple, objective and reproducible system to describe glioblastoma multiforme (GBM) represents a major limitation in comparative effectiveness research. The objectives of this study were therefore to develop such a grading system and to validate it on patients who underwent surgical resection. A systematic review of the literature was performed to identify features on pre-operative magnetic resonance imaging (MRI) that predict the surgical outcome of patients with GBM. In all, the five most important features of GBM on pre-operative MRI were as follows: periventricular or deep location, corpus callosum or bilateral location, eloquent location, size and associated oedema. These were then used to develop a grading system. To validate this grading system, a retrospective cohort study of all adult patients with supratentorial GBM who underwent surgical resection between the 1 January 2014 and the 31 June 2015 was performed. There was a substantial agreement between the two neurosurgeons grading GBM (Cohen's κ was 0.625; standard error 0.066). High-complexity lesions were significantly less likely to result in complete resection of contrast-enhancing tumour than low-complexity lesions (50.0 versus 3.4%; p = 0.0007). The proposed grading system may allow for the standardised communication of anatomical features of GBM identified on pre-operative MRI.

Long-term follow-up of 123 patients with adenocarcinoma of the sinonasal tract treated with endoscopic resection and postoperative radiation therapy.

BACKGROUND: Most series about endoscopic resection of adenocarcinomas of the sinonasal tract present outcome data from a small heterogeneous group of patients with a relatively short follow-up period and a wide variety of histological subtypes and treatment protocols. This relatively large study with a very homogeneous study population updates our experience with a stable treatment protocol looking at survival rates, surgical technique, and prognostic factors. METHODS: We conducted a retrospective analysis of the medical records of 123 patients with adenocarcinoma of the intestinal type primarily treated with endoscopic resection and postoperative radiotherapy (RT) in a single tertiary referral center during the period 1992 to 2010. RESULTS: Mean follow-up was 66 months and median follow-up was 54 months. Mean and median follow-up of the subgroup of patients alive at the end of follow-up was 74 months and 61 months, respectively. At 5-years of follow-up, overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) were 68%, 82%, and 62% respectively. At 10-year follow-up, these numbers were 51%, 74%, and 45%, respectively. Prognostic factors for treatment outcome are predominantly local recurrence, development of distant metastasis, T classification, histopathological classification, and the center where the first surgery was performed. CONCLUSION: This large study of sinonasal adenocarcinoma primarily treated with endoscopic resection and RT confirms that this approach results in good oncologic and functional outcome.

Outcome evaluation of the dizziness handicap inventory in an outpatient vestibular clinic.

BACKGROUND: The DHI is a widely used questionnaire for the evaluation of the self-reported disability in patients with dizziness and balance problems. OBJECTIVE: To investigate the relationship between the DHI scores and demographic, symptomatic and diagnostic parameters. METHODS: Retrospective study in 568 patients with balance problems. RESULTS: We observed a total of 61.3% of patients with moderate (DHI total score between 30 and 59) to severe (DHI total score between 60 and 100) disability.Patients with long-standing complaints (lasting longer than 3 months) experience their self-reported disability to a greater extent than patients with new onset pathology (illness duration of one month and less). Moreover, patients suffering from continuous complaints have a larger DHI score than patients with shorter symptom duration. The first effect (new onset vs. long-standing pathology) is primarily caused by emotional factors, the latter effect (symptom duration) is attributable to functional and physical factors, not to emotional aspects. Patients with daily and weekly complaints have larger DHI scores than patients who reported only one episode. Female patients reported larger DHI scores than males. We found no effect of age, diagnostic group (no diagnosis, episodic, acute or chronic vestibular syndrome) or reported symptoms on the DHI scores. CONCLUSIONS: The information retrieved from the DHI questionnaire is complementary to the information obtained from clinical investigation and diagnostic tests and therefore is an essential tool in a vestibular clinic.

The Bony Obliteration Tympanoplasty in Pediatric Cholesteatoma: Long-term Safety and Hygienic Results.

OBJECTIVE: To present the safety and hygienic results of a 5-year longitudinal study in a pediatric population undergoing surgery for extensive cholesteatoma using a canal wall up approach with bony obliteration of the mastoid and epitympanic space. STUDY DESIGN: Retrospective consecutive study. PATIENTS: Thirty-three children (≤18 yr) undergoing surgery for cholesteatoma (34 ears) between 1997 and 2009. INTERVENTIONS: Therapeutic. SETTING: Tertiary referral center. MAIN OUTCOME MEASURES: 1) Residual and recurrent cholesteatoma rates at 5-year postsurgery, 2) postoperative waterproofing and hygienic status of the ear, and 3) required operation rate to achieve the safety and hygienic goals. RESULTS: At 5 years no patients were lost in follow-up. This consecutive series design is rare in chronical otitis media treatment reporting. The standard residual rate at 5 years was 5.8%, representing two residual cholesteatomas in the middle ear. The standard recurrence rate at 5 years was 2.9%, representing one recurrent cholesteatoma. At 5-year follow-up all ears were free of otorrhea and waterproof and all external ear canals were patent and self-cleaning. The operation rate to reach this safety and hygienic status was 1.5 operations per ear at 5-year follow-up. CONCLUSION: The use of a canal wall up approach with obliteration of the mastoid cavity and epitympanic space to surgically treat cholesteatoma in children results in low residual and recurrence rates and a high rate of trouble-free ears in the long term.

Validity and Test-Retest Reliability of the Dutch Version of the Chronic Otitis Media Questionnaire 12 (COMQ-12).

OBJECTIVE: To test the validity and test-retest reliability of the Dutch translation of the Chronic Otitis Media Questionnaire 12 (COMQ-12). MATERIALS AND METHODS: Thirty-five healthy individuals with no history of chronic otitis media (COM) received the questionnaire as well as a group of 35 patients with complaints of COM. The healthy participants had to complete the questionnaire twice (control group 1 and control group 2) to estimate the test-retest reliability, and their scores were compared with those of the patients (group 3) to test the validity. RESULTS: The overall COMQ-12 score in control group 1 ranged from 0 to 11, in control group 2 from 0 to 6, and in group 3 from 7 to 46. The mean score in control group 1 was 1.43 [standard deviation (SD) 2.30], 1.34 in control group 2 (SD 2.06), and 27.80 in group 3 (SD 10.51). A comparison of the absolute COMQ-12 scores of the two control groups and the patient group showed a significantly higher COMQ-12 score in patients with COM than in controls. The diagnostic accuracy was investigated, and a COMQ-12 cut-off score of 8 was found to have a near-perfect sensitivity and specificity in distinguishing between the presence and absence of COM. The single-measures intraclass correlation coefficient for absolute agreement (ICCAA) was 0.859 (with a 95% confidence interval from 0.738 to 0.926). This clearly exceeded the ICC threshold for acceptable reliability (ICC≥0.75) and therefore confirmed that there was reasonable test-retest reliability when applying the questionnaire to control subjects. CONCLUSION: The Dutch version of the COMQ-12 has good validity, diagnostic accuracy, and test-retest reliability.

Intracerebral multifocal Rosai-Dorfman disease.

We report a rare occurrence of intracranial Rosai-Dorfman disease (RDD), in a young patient with multiple bilateral intracerebral lesions, and discuss her management. RDD is an histiocytic proliferative disorder, which seldom presents with intracranial pathology. Intraparenchymal RDD without concurrent systemic features is rare. This 31-year old woman presented with two focal seizures, but no peripheral lymphadenopathy, and no significant systemic abnormalities. Preoperative imaging showed intrinsic space-occupying lesions in the left frontal lobe, and right parietal and right inferior frontal white matter. She underwent excision of the peripherally located left frontal lesion, and aside from a five-day course of postoperative dexamethasone, received no further active treatment. Histopathological analysis revealed the characteristic features of RDD. Postoperative imaging, taken at 10 weeks and 12 months, demonstrated resolution of all three lesions. This patient had a rare multifocal, bilateral, intracerebral RDD, illustrating that although a histological diagnosis is necessary, further treatment may not be required.

Diagnostic implications of histological analysis of neurosurgical aspirate in addition to routine resections.

Many neurosurgical centers use surgical aspirators to remove brain tumor tissue. The resulting aspirate consists of fragmented viable tumor, normal or tumor-infiltrated brain tissue as well as necrotic tissue, depending on the type of tumor. Typically, such fragmented aspirate material is collected but discarded and not included when making the histopathological diagnosis. Whereas the general suitability of surgical aspirate for histological diagnosis and immunohistochemical staining has been reported previously, we have systematically investigated whether the collection and histological examination of surgical aspirate has an impact on diagnosis, in particular on the tumor grading, by providing additional features. Surgical and aspirate specimens from 85 consecutive neurosurgical procedures were collected and routinely processed. Sixty-five of the 85 specimens were intrinsic brain tumors and the remainder consisted of metastatic tumors, meningiomas, schwannomas and lymphomas. Important diagnostic features seen in surgical aspirate were microvascular proliferation (n = 3), more representative necrosis (n = 2), and gemistocytic component (n = 2). In one case, microvasular proliferations were seen in the aspirate only, leading to a change of diagnosis. Collection of surgical aspirate also generates additional archival material which can be microdissected and used for tissue microarrays or for molecular studies.

External ventricular drain insertion accuracy: is there a need for change in practice?

OBJECTIVE: Free-hand insertion of an external ventricular drain (EVD) is a common emergency neurosurgical procedure, mostly performed for critically ill patients. Although EVD complications have been studied thoroughly, the accuracy of EVD positioning has been audited only occasionally. METHODS: Post-EVD insertion computed tomographic scans performed in our unit over a 2-year period were analyzed for EVD tip location and intracranial catheter length. RESULTS: A total of 183 post-EVD insertion scans were reviewed. Of those, 73 EVD tips (39.9%) were in the ipsilateral frontal horn of the lateral ventricle (the desired target); of those, 18 (25%) required EVD revision/reinsertion. Of the others, 35 (19.1%) were in the third ventricle, 33 (18%) in the body of the lateral ventricle, 19 (10.4%) in the subarachnoid space, 5 (2.7%) in the contralateral frontal horn, and 18 (9.8%) within the brain parenchyma. When the EVD tip was outside the desired target, 44 of the patients (40%) required EVD revision/reinsertion procedure (P = 0.0383). CONCLUSION: Free-hand insertion of an EVD is an inaccurate procedure, and further studies are required to assess the accuracy and feasibility of the routine use of neuronavigation, ultrasonography, or other guidance techniques and the possible implication of the decreasing revision rate, complications, and length of hospital stay.