Survival and complications following supra- and infratentorial brain metastasis resection.

OBJECTIVE: 15-30% of primary cancers metastasise to the brain. Of these, 10-25% involve the posterior fossa. It remains unclear whether patients undergoing resection for infratentorial brain metastases experience poorer prognosis than those with supratentorial lesions. We compare the post-operative outcomes of these two groups. METHODS: We searched the electronic health records of all patients undergoing brain metastases resection at our regional neurosurgical centre between February 2014 and August 2019. Clinical data was collected on 85 consecutive patients (61 supratentorial, 24 infratentorial metastases). Outcome measures included overall survival, post-operative complications, and performance status. Patients were followed up until 21/04/2020. RESULTS: Median post-operative survival of patients with supratentorial metastases was 323 days (95% CI 235-411), compared to 277 days (95% CI 195-359) for those with infratentorial metastases. These two groups experienced comparable survival (log rank = 0.276, p = 0.60) on univariate analysis. Infratentorial metastasis location was not associated with a change in survival using a Cox proportional hazards model incorporating age, sex and extracranial disease activity (HR = 1.39, 95% CI 0.777-2.486) (p = 0.27). However, neurological and non-neurological post-operative complications were more frequent in patients with infratentorial metastases (neurological = 21% vs 13%, non-neurological = 25% vs 2%, p = 0.002). CONCLUSION: Patients with supra- and infratentorial metastases experienced comparable post-operative survival but posterior fossa metastasis location was associated with a 2.5 times higher risk of neurological and/or non-neurological post-operative complications. A better understanding of the precise indications for safe and effective surgical intervention for posterior fossa metastases is required.

Presentation, management, and outcomes of cauda equina syndrome up to one year after surgery, using clinician and participant reporting: A multi-centre prospective cohort study.

Background: Cauda equina syndrome (CES) results from nerve root compression in the lumbosacral spine, usually due to a prolapsed intervertebral disc. Evidence for management of CES is limited by its infrequent occurrence and lack of standardised clinical definitions and outcome measures. Methods: This is a prospective multi-centre observational cohort study of adults with CES in the UK. We assessed presentation, investigation, management, and all Core Outcome Set domains up to one year post-operatively using clinician and participant reporting. Univariable and multivariable associations with the Oswestry Disability Index (ODI) and urinary outcomes were investigated. Findings: In 621 participants with CES, catheterisation for urinary retention was required pre-operatively in 31% (191/615). At discharge, only 13% (78/616) required a catheter. Median time to surgery from symptom onset was 3 days (IQR:1-8) with 32% (175/545) undergoing surgery within 48 h. Earlier surgery was associated with catheterisation (OR:2.2, 95%CI:1.5-3.3) but not with admission ODI or radiological compression. In multivariable analyses catheter requirement at discharge was associated with pre-operative catheterisation (OR:10.6, 95%CI:5.8-20.4) and one-year ODI was associated with presentation ODI (r = 0.3, 95%CI:0.2-0.4), but neither outcome was associated with time to surgery or radiological compression. Additional healthcare services were required by 65% (320/490) during one year follow up. Interpretation: Post-operative functional improvement occurred even in those presenting with urinary retention. There was no association between outcomes and time to surgery in this observational study. Significant healthcare needs remained post-operatively. Funding: DCN Endowment Fund funded study administration. Castor EDC provided database use. No other study funding was received.

Demographics of Cauda Equina Syndrome: A Population-Based Incidence Study.

INTRODUCTION: Cauda equina syndrome (CES) has significant medical, social, and legal consequences. Understanding the number of people presenting with CES and their demographic features is essential for planning healthcare services to ensure timely and appropriate management. We aimed to establish the incidence of CES in a single country and stratify incidence by age, gender, and socioeconomic status. As no consensus clinical definition of CES exists, we compared incidence using different diagnostic criteria. METHODS: All patients presenting with radiological compression of the cauda equina due to degenerative disc disease and clinical CES requiring emergency surgical decompression during a 1-year period were identified at all centres performing emergency spinal surgery across Scotland. Initial patient identification occurred during the emergency hospital admission, and case ascertainment was checked using ICD-10 diagnostic coding. Clinical information was reviewed, and incidence rates for all demographic and clinical groups were calculated. RESULTS: We identified 149 patients with CES in 1 year from a total population of 5.4 million, giving a crude incidence of 2.7 (95% CI: 2.3-3.2) per 100,000 per year. CES occurred more commonly in females and in the 30-49 years age range, with an incidence per year of 7.2 (95% CI: 4.7-10.6) per 100,000 females age 30-39. There was no association between CES and socioeconomic status. CES requiring catheterization had an incidence of 1.1 (95% CI: 0.8-1.5) per 100,000 adults per year. The use of ICD-10 codes alone to identify cases gave much higher incidence rates, but was inaccurate, with 55% (117/211) of patients with a new ICD-10 code for CES found not to have CES on clinical notes review. CONCLUSION: CES occurred more commonly in females and in those between 30 and 49 years and had no association with socioeconomic status. The incidence of CES in Scotland is at least four times higher than previous European estimates of 0.3-0.6 per 100,000 population per year. Incidence varies with clinical diagnostic criteria. To enable comparison of rates of CES across populations, we recommend using standardized clinical and radiological criteria and standardization for population structure.

Neurorobotic Models of Neurological Disorders: A Mini Review.

Modeling is widely used in biomedical research to gain insights into pathophysiology and treatment of neurological disorders but existing models, such as animal models and computational models, are limited in generalizability to humans and are restricted in the scope of possible experiments. Robotics offers a potential complementary modeling platform, with advantages such as embodiment and physical environmental interaction yet with easily monitored and adjustable parameters. In this review, we discuss the different types of models used in biomedical research and summarize the existing neurorobotics models of neurological disorders. We detail the pertinent findings of these robot models which would not have been possible through other modeling platforms. We also highlight the existing limitations in a wider uptake of robot models for neurological disorders and suggest future directions for the field.

Are we neglecting sexual function assessment in suspected cauda equina syndrome?

OBJECTIVES: We assessed the documentation rates of signs and symptoms, including sexual function, in patients with suspected cauda equina syndrome and whether they can be improved by increasing local awareness. PATIENTS AND METHODS: We reviewed all electronic records of patients referred with suspected CES who required urgent MRI to our regional service over a 2 month period. We recorded the documentation rates of clinical signs and symptoms. The results were presented locally to increase awareness. A further 2 month period was then re-audited. 120 patients in total were included across both time periods. Chi-squared was used to compare documentation rates between time periods. RESULTS: 25 of 120 patients had radiological cauda equina compression. Lower limb neurology, urinary function and saddle sensation were almost universally documented. After the intervention, there was a significant increase (p < 0.05) in the documentation of bowel function and post-void residual but not sexual function. Sexual function was poorly documented with rates of 3% and 11% throughout the two audited periods. CONCLUSION: Certain clinical features of CES are well documented. Increasing awareness may improve documentation of certain symptoms/signs in patients with suspected cauda equina syndrome. Sexual function was poorly documented and increasing awareness alone is an inadequate intervention.

Does a history of lumbar spine surgery predict radiological cauda equina compression in patients undergoing MRI for suspected cauda equina syndrome?

Background: The clinical symptoms and signs of Cauda equina syndrome (CES) are non specific and poorly predictive of cauda equina compression on MRI. We aimed to establish whether a history of lumbar spine surgery predicts cauda equina compression on MRI in those presenting with suspected CES.Methods: A retrospective electronic record review was undertaken of 276 patients referred with clinically suspected CES who underwent a lumbosacral spine MRI. Those with a history of prior lumbar surgery were compared to those without. The likelihood of cauda equina compression was compared between the two groups.Results: About 78/276 (28%) patients with suspected CES had radiological compression of the cauda equina and went on to surgical decompression. A total of 54 (20%) patients had undergone prior lumbar surgery. Patients with a history of lumbar surgery were less likely to have cauda equina compression on MRI (χ2 - p = .035). Twenty six (9%) patients presented more than once with suspected CES. Patients with a history of lumbar surgery were more likely to re-present with suspected CES (χ2 - p = .002).Conclusions: Prior lumbar surgery was associated with a higher frequency of re-presentation with clinically suspected CES but a lower frequency of radiological cauda equina compression.

Compressive Pressure Versus Time in Cauda Equina Syndrome: A Systematic Review and Meta-Analysis of Experimental Studies.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To examine the relationship between compressive pressure and its duration in cauda equina compression, and the effects of subsequent decompression, on neurophysiological function, and pathophysiology in animal studies. We further aim to investigate these relationships with systemic blood pressure to assess whether a vascular component in the underlying mechanism may contribute to the clinical heterogeneity of this disease. SUMMARY OF BACKGROUND DATA: The complex relationship between preoperative factors and outcomes in cauda equina syndrome (CES) suggests heterogeneity within CES which may inform better understanding of pathophysiological process, their effect on neurological function, and prognosis. METHODS: Systematic review identified 17 relevant studies including 422 animals and reporting electrophysiological measures (EP), histopathology, and blood flow. Modeling using meta-regression analyzed the relationship between compressive pressure, duration of compression, and electrophysiological function in both compression and decompression studies. RESULTS: Modeling suggested that electrophysiological dysfunction in acute cauda equina compression has a sigmoidal response, with particularly deterioration when mean arterial blood pressure is exceeded and, additionally, sustained for approximately 1 hour. Accounting for pressure and duration may help risk-stratify patients pre-decompression. Outcomes after decompression appeared to be related more to the degree of compression, where exceeding systolic blood pressure tended to result in an irreversible lesion, rather than duration of compression. Prognosis was most strongly associated with residual pre-decompression function. CONCLUSION: Compressive pressure influences effects and outcomes of cauda equina compression. We suggest the presence of two broad phenotypic groups within CES defined by the degree of ischaemia as a potential explanatory pathophysiological mechanism. LEVEL OF EVIDENCE: 1.

Understanding cauda equina syndrome: protocol for a UK multicentre prospective observational cohort study.

INTRODUCTION: Cauda equina syndrome (CES) is a potentially devastating condition caused by compression of the cauda equina nerve roots. This can result in bowel, bladder and sexual dysfunction plus lower limb weakness, numbness and pain. CES occurs infrequently, but has serious potential morbidity and medicolegal consequences. This study aims to identify and describe the presentation and management of patients with CES in the UK. METHODS AND ANALYSIS: Understanding Cauda Equina Syndrome (UCES) is a prospective and collaborative multicentre cohort study of adult patients with confirmed CES managed at specialist spinal centres in the UK. Participants will be identified using neurosurgical and orthopaedic trainee networks to screen referrals to spinal centres. Details of presentation, investigations, management and service usage will be recorded. Both patient-reported and clinician-reported outcome measures will be assessed for 1 year after surgery. This will establish the incidence of CES, current investigation and management practices, and adherence to national standards of care. Outcomes will be stratified by clinical presentation and patient management. Accurate and up to date information about the presentation, management and outcome of patients with CES will inform standards of service design and delivery for this important but infrequent condition. ETHICS AND DISSEMINATION: UCES received a favourable ethical opinion from the South East Scotland Research Ethics Committee 02 (Reference: 18/SS/0047; IRAS ID: 233515). All spinal centres managing patients with CES in the UK will be encouraged to participate in UCES. Study results will be published in medical journals and shared with local participating sites. TRIAL REGISTRATION NUMBER: ISRCTN16828522; Pre-results.

Cytotoxicity of ultraviolet-C radiation on a heterogeneous population of human glioblastoma multiforme cells: Meta-analysis.

INTRODUCTION: Current treatment strategies for glioblastoma multiforme are limited due to early recurrence and heterogeneity of the cell population that causes a varied response to treatment. Ultraviolet-C (UVC) radiation may be a potential adjuvant treatment that could theoretically be delivered locally by implantable micro-electromechanical systems that sense and kill early recurrence and/or minimally residual cancer. in vitro irradiation experiments are limited because they commonly use a single cell line. Therefore other methods are required to investigate cytotoxicity across a heterogeneous population of GBM. METHODS: A meta-analysis was conducted to assess the cytotoxic effects of UVC radiation on human GBM cell lines, with or without genetic modification, in monolayer to simulate a heterogeneous model. 16 publications were included using 14 different cell lines and 19 gene vectors. Effect sizes were calculated for cell survival, viability, apoptosis and proliferation. Univariate meta-regression was used to investigate the effects of radiant exposure (J/m2) and timing on cytotoxicity. RESULTS: UVC resulted in a 70.9% (CI: 63.6%-78.2%) reduction in survival, 16.6% (CI: 10.8%-22.4%) increase in apoptosis, 32.0% (CI: 9.95%-54.2%) reduction in viability, and 413.8% (CI: 95.7%-731.9%) reduction in proliferation of GBM cell lines compared to controls. Radiant exposure was significantly associated with survival (R2 = 0.486, p < 0.0001) but not with apoptosis or viability. CONCLUSIONS: This study provides more data on the therapeutic translational potential of UVC to a more clinically-realistic context. Overall, UVC is cytotoxic to GBM cell lines in aggregate and may be clinically useful when combined with genetic modification or other adjuvant treatments.

The clinical features and outcome of scan-negative and scan-positive cases in suspected cauda equina syndrome: a retrospective study of 276 patients.

BACKGROUND: The majority of patients presenting with suspected clinical cauda equina syndrome (CES) have no identifiable structural cause for their symptoms ('scan-negative' CES). Understanding these patients aids clinical differentiation and management in CES. METHODS: A retrospective electronic note review was undertaken of patients presenting with suspected CES, defined as ≥ 1 of acute bladder, bowel, sexual dysfunction or saddle numbness, to a regional neurosciences centre. We investigated radiology, clinical features, psychiatric and functional disorder comorbidities and outcome of patients with 'scan-negative' CES and patients with MRI confirmed compression of the cauda equina ('scan-positive' CES). RESULTS: 276 patients were seen over 16 months. There were three main radiologically defined patient groups: (1) 'scan-positive' CES (n = 78, mean age 48 years, 56% female), (2) 'scan-negative' CES without central canal stenosis but with lumbosacral nerve root compression not explaining the clinical presentation (n = 87, mean age 43 years, 68% female) and (3) 'scan-negative' CES without neural compromise (n = 104, mean age 42 years, 70% female). In the two 'scan-negative' groups (no neural compromise and nerve root compression), there were higher rates of functional disorders (37% and 29% vs. 9%), functional neurological disorders (12% and 11% vs 0%) and psychiatric comorbidity (53% and 40% vs 20%). On follow-up (mean 13-16 months), only 1 of the 191 patients with 'scan-negative' CES was diagnosed with an explanatory neurological disorder (transverse myelitis). CONCLUSIONS: The data support a model in which scan-negative cauda equina syndrome arises as an end pathway of acute pain, sometimes with partly structural findings and vulnerability to functional disorders.

The Influence of Corneal Biomechanical Properties on Intraocular Pressure Measurements Using a Rebound Self-tonometer.

PURPOSE: The purpose of this study was to examine the effect of corneal biomechanical properties on intraocular pressure (IOP) measurements obtained using a rebound self-tonometer (Icare HOME) compared with Goldmann applanation tonometry (GAT). METHODS: An observational study of 100 patients with glaucoma or ocular hypertension. All had a comprehensive ophthalmic examination and standard automated perimetry. IOP was assessed by GAT, Icare HOME and Ocular Response Analyzer, which was also used to assess corneal hysteresis (CH) and corneal resistance factor (CRF). Central corneal thickness (CCT) was recorded. RESULTS: Mean (±SD) IOP measurements were 14.3±3.9 and 11.7±4.7 mm Hg using GAT and Icare HOME, respectively. Average CCT, CRF, and CH were 534.5±37.3 µm, 9.0±1.7 mm Hg, and 9.4±1.5 mm Hg, respectively. The mean difference between Icare HOME and GAT was -2.66±3.13 mm Hg, with 95% limits of agreement of -8.80 to 3.48 mm Hg, however, there was evidence of proportional bias. There was negative correlation between IOP and CH [5.17 mm Hg higher Icare HOME IOP (P=0.041, R=0.029) and 7.23 mm Hg higher GAT IOP (P=0.008, R=0.080) for each 10 mm Hg lower CH], whereas thinner CCT was significantly associated with lower IOP (P<0.001, R=0.14 for Icare HOME and P<0.001, R=0.08 for GAT). In multivariable analysis, although CRF and CH remained associated with IOP measured using either GAT or Icare HOME, CCT was no longer significant. CONCLUSION: IOP measurements obtained using a self-tonometer, similar to GAT, were more influenced by overall corneal biomechanics than CCT.

Chondroitinase ABC for neurological recovery after acute brain injury: systematic review and meta-analyses of preclinical studies.

OBJECTIVES: Damage to critical brain regions causes deficits in important neurological functions. Chondroitinase ABC (ChABC) has been shown to promote neuroplasticity and may ameliorate neurological deficits caused by disease or trauma. This systematic review identifies and evaluates preclinical studies of ChABC as a treatment for acute brain injury. METHODS: Four databases were searched for studies relating to ChABC and brain or brain injuries. Controlled studies in mammals with acute brain injuries treated with ChABC were included in meta-analyses of neurobehavioural outcomes. Means and standard deviations from the fifth day of treatment were extracted, and normalised mean differences were calculated. RESULTS: Of 775 identified records, 16 studies administered ChABC after acute brain injury, of which 9 reported neurobehavioural outcomes. The estimated treatment effect on neurological recovery over the duration of included studies was 49.4% (CI: 30.3-68.4% with Hartung-Knapp-Sidik-Jonkman adjustment, p = 0.0002). The mechanisms of action may involve decreasing astroglial scar formation, promoting neuronal sprouting, and selective synaptic strengthening of sprouting neurites and activated neural pathways. CONCLUSIONS: The summary of published evidence suggests that ChABC treatment is effective in improving neurological outcomes in preclinical models of acute brain injury. However, more studies are needed for better assessment of the specific translational potential of ChABC. ABBREVIATIONS: AVM - Arteriovenous Malformation; ChABC - Chondroitinase ABC; CI - Confidence Interval; CSPG - Chondroitin Sulphate Proteoglycans; HKSJ - Hartung-Knapp-Sidik-Jonkman; MCA - Middle Cerebral Artery; NMD - Normalised Mean Difference; NSPC - Neural Stem/Progenitor Cells; PI - Prediction Interval; SD - Standard Deviation; SMD - Standardised Mean Difference; TBI - Traumatic Brain Injury.

Measurement of Intraocular Pressure by Patients With Glaucoma.

Importance: The ability of patients to measure their own intraocular pressure (IOP) would allow more frequent measurements and better appreciation of peak IOP and IOP fluctuation. Objective: To examine whether patients with glaucoma can perform self-tonometry using a rebound tonometer and examine patient acceptability. Design, Setting, and Participants: An observational study in which IOP was assessed using Goldmann applanation tonometry and a rebound tonometer. Consecutive patients were provided with a patient information sheet and those consenting to take part in the study received standardized self-tonometry training and were then instructed to measure their own IOP under observation. This study was conducted at a glaucoma clinic at a university hospital from March 1, 2016, to December 30, 2016, and included both eyes of 100 patients with glaucoma or ocular hypertension. Main Outcomes and Measures: The percentage of patients who could successfully perform self-tonometry. Complete success was defined by a good technique and an IOP reading within 5 mm Hg of that obtained by a clinician using the same device. A 3-item questionnaire was used to examine perceptions of self-tonometry among patients. Results: Among the 100 patients, the mean (SD) age was 67.5 (10.9) years (53% female). A total 73 of 100 patients (73%) met the complete success criteria. An additional 6 patients could use the device but had IOP readings greater than 5 mm Hg different from those obtained by the clinician. On average, IOP by the rebound tonometer was 2.66 mm Hg lower than Goldmann applanation tonometry (95% limits of agreement, -3.48 to 8.80 mm Hg). The IOPs with the rebound tonometer were similar whether obtained by self-tonometry or investigator, with excellent reproducibility with an intraclass correlation coefficient of 0.903 (95% CI, 0.867-0.928). A total of 56 of 79 successful or partially successful patients (71%) felt self-tonometry was easy, with 73 of 79 (92%) reporting self-tonometry to be comfortable, and a similar number happy to perform self-tonometry in the future. Conclusions and Relevance: Most patients could perform self-tonometry and the method was acceptable to patients. Self-tonometry has the potential to improve patient engagement, while also providing a more complete picture of IOP changes over time.

Effects of Ultraviolet Radiation on Glioma: Systematic Review.

Glioblastoma multiforme is the most aggressive primary brain tumor. Treatment is largely palliative, with current strategies unable to prevent inevitable tumor recurrence. Implantable micro-electromechanical systems are becoming more feasible for the management of several human diseases. These systems may have a role in detecting tumor recurrence and delivering localized therapies. One potential therapeutic tool is ultraviolet (UV) light. This systematic review assesses the effects of UV light on glioma cells. A total of 47 publications are included. The large majority were in vitro experiments conducted on human glioblastoma cell lines in monolayer. In these cells, UV light was shown to induce apoptosis and the expression of genes or activation of proteins that modulate cell death, repair, and proliferation. The nature and magnitude of cellular response varied by UV wavelength, dose, cell line, and time after irradiation. UVC (wavelength 100-280 nm) was most effective at inducing apoptosis, and this effect was dose dependent. The included studies had varied methodologies, complicating reconciliation of results. Further work will be required to determine the best regime of UV irradiation for therapeutic use. J. Cell. Biochem. 118: 4063-4071, 2017. © 2017 Wiley Periodicals, Inc.

A national survey of the use of pachymeters by optometrists in Scotland: experience, views and barriers to use.

PURPOSE: Thin central corneal thickness (CCT) is a risk factor for glaucoma. In 2016 all optometry practices in Scotland were provided with pachymeters aiming to improve risk assessment and accuracy of referrals to secondary care. We examined optometrists' experience and views of pachymetry, including perceived barriers to pachymetry in primary care. METHODS: A questionnaire was sent using the REDCap electronic data capture tool to all 1264 optometrists registered with NHS Education for Scotland (NES). The questionnaire evaluated year of qualification, previous pachymetry training, confidence performing and interpreting pachymetry, and perceived indications for and barriers to use. RESULTS: Respondents numbered 418 out of 1264 (33%) optometrists, of whom 56% had previous training in pachymetry. Those that had previous training were significantly more likely to report pachymetry to be useful, with median (inter-quartile range) usefulness score of 86 (71-98) where 0 indicated not at all useful, and 100 extremely useful, vs 76 (58-90), Wilcoxon-Mann-Whitney test, z = -4.67, p < 0.01. There are no valid scales for adjusting intraocular pressure (IOP) using CCT, however 45% of respondents reported using a scale. Optometrists planned to use pachymetry when assessing patients with ocular hypertension or suspected glaucoma. The greatest perceived barrier was the process of decontaminating or cleaning the pachymeter between patients, followed by lack of time and lack of training. CONCLUSIONS: Although the majority of optometrists were interested in performing pachymetry, many lacked confidence in performing and interpreting the results. Forty-one percent of those who reported training in pachymetry still used non-validated scales to convert IOP measurements illustrating the need for further training.