Imaging incidence and type in primary care patients with low back pain: a cross-sectional study on new referrals to an Australian specialist spinal surgical centre.

Introduction Low back pain (LBP) is common and a significant cause of morbidity. Many patients receive inappropriate imaging for LBP in primary care. Aim To explore the incidence and type of spinal imaging conducted for LBP patients referred from general practice for specialist surgical opinion, and evaluate whether imaging conformed to clinical guidelines. Methods Audit of a sequential cohort (n = 100) of new LBP patients referred from primary care for specialist opinion at a suburban Australian capital city independent Spinal Centre. Results In the 6 months before referral, 90% (95% CI 83-95%) of patients underwent spinal imaging. Imaging was performed in 95% of those who did and 79% of those who did not meet guidelines for radiological investigation. 35% of patients were inappropriately imaged and 3% inappropriately not imaged. Spinal computed tomography (CT) imaging was used in 52% of patients, magnetic resonance imaging (MRI) in 42% and image-guided lumbar spinal interventional procedures in 28%. Discussion Most patients with LBP referred for surgical opinion have diagnostic radiological investigations whether or not it is indicated by clinical guidelines. The more frequent use of spinal CT compared to MRI may be due to idiosyncrasies of the Australian Medicare Benefits Schedule (MBS) rebate system. The findings of this pilot study provide support for the changes recommended by the 2016 MBS Review Taskforce on LBP that permit GP access to subsidised lumbar MRI, while constraining access to lumbar CT, and provide novel data about spinal imaging and practice in this cohort of patients.

Using general practitioners with an extended role in spinal practice for the initial assessment of patients referred to spinal surgeons: preliminary experience and challenges.

AIM: To describe experience using general practitioners (GPs), with an extended role (GPwER) in spinal medicine, to expedite assessment, triage, and management of patients referred from primary care for specialist spinal surgical opinion. BACKGROUND: Low back and neck pain are common conditions in primary care. Indiscriminate or inappropriate referral to a spinal surgeon contributes to long waiting times. Previous attempts at triaging patients who really require a surgical opinion have used practice nurses, physiotherapists, clinical algorithms, and interdisciplinary screening clinics. METHODS: Within the setting of an independent spinal care centre, we have used GPs specially trained in spinal practice to expedite the assessment and triage of new referrals between 2015 and 2021. We reviewed feedback from a Patient Satisfaction Questionnaire and the postgraduate backgrounds, training, practice with regard to triage of new referrals, and experiences of the GPs who were recruited. FINDINGS: Six GPwER had a mean of 26 years of postgraduate experience before appointment (range 10-44 years). The first four GPwER, appointed between 2015 and 2018, underwent an ad hoc in-house, interdisciplinary training programme and saw 2994 new patients between 2016 and 2020. After GPwER, assessment in only 18.9% (range 12.6 to 22.7%) of these patients was a spinal surgical opinion deemed necessary. Waiting times to see the spinal surgeon remained at 6-8 weeks despite a three-fold annual increase (from 340 to 1058) in new referrals. A Patient Satisfaction Questionnaire revealed high levels of satisfaction with the performances of the GPwER across seven dimensions. A dedicated training programme was designed in 2020, and the last two appointees underwent 20 h of clinical teaching prior to practice. Initial experience using GPwER, here termed 'Spinal Clinicians', suggests they are efficient at screening for patients needing spinal surgical referral. Establishing a recognised training programme, assessment, and certification for these practitioners are the next challenges.

Clinical utility and reproducibility of surface electromyography in individuals with chronic low back pain: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Chronic low back pain (CLBP) is one of the most common disorders presenting in primary healthcare. Kinematic studies of low lumbar pelvic mobility allied with surface electromyography (sEMG) may assist in the assessment and management of CLBP. However, the applicability in the use of sEMG in the clinical setting remains uncertain. In this protocol, we aim to review the clinical utility and reproducibility of the sEMG component of these kinematic studies in patients with CLBP. METHODS AND ANALYSIS: This protocol was informed by the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) and results will be reported in line with the PRISMA. Searches will be conducted on PubMed, Scopus, Web of Science, Embase, CINAHL and Google Scholar databases, along with a comprehensive review of grey literature. Two reviewers will conduct the searches and independently screen them, according to title and abstract. Two independent reviewers will then assess the full-text versions of those selected articles and assess the risk of bias using the defined protocol inclusion criteria. The risk of bias within the studies included will be assessed via the Quality Assessment of Diagnostic Accuracy Studies tool, V.2 and the Grading of Recommendations Assessment, Development and Evaluation guidelines will be used to assess certainty of evidence for recommendations based on the risk of bias findings. Meta-analysis will be conducted where appropriate on groups of studies with low heterogeneity. In instances of higher heterogeneity, meta-synthesis will instead be completed, comparing results in terms of increased or decreased clinical utility and/or reproducibility of sEMG. ETHICS AND DISSEMINATION: Ethics approval was not required for this research. It is anticipated that the results will influence the use, interpretation and further development of sEMG in management and assessment of these patients. PROSPERO REGISTRATION NUMBER: CRD42021273936.

A structural and functional magnetic resonance imaging dataset of brain tumour patients.

We collected high resolution structural (T1, T2, DWI) and several functional (BOLD T2*) MRI data in 22 patients with different types of brain tumours. Functional imaging protocols included a motor task, a verb generation task, a word repetition task and resting state. Imaging data are complemented by demographics (age, sex, handedness, and pathology), behavioural results to motor and cognitive tests and direct cortical electrical stimulation data (pictures of stimulation sites with outcomes) performed during surgery. Altogether, these data are suited to test functional imaging methods for single subject analyses, in particular methods that focus on locating eloquent cortical areas, critical functional and/or structural network hubs, and predict patient status based on imaging data (presurgical mapping).

Evaluation of a pre-surgical functional MRI workflow: From data acquisition to reporting.

PURPOSE: Present and assess clinical protocols and associated automated workflow for pre-surgical functional magnetic resonance imaging in brain tumor patients. METHODS: Protocols were validated using a single-subject reliability approach based on 10 healthy control subjects. Results from the automated workflow were evaluated in 9 patients with brain tumors, comparing fMRI results to direct electrical stimulation (DES) of the cortex. RESULTS: Using a new approach to compute single-subject fMRI reliability in controls, we show that not all tasks are suitable in the clinical context, even if they show meaningful results at the group level. Comparison of the fMRI results from patients to DES showed good correspondence between techniques (odds ratio 36). CONCLUSION: Providing that validated and reliable fMRI protocols are used, fMRI can accurately delineate eloquent areas, thus providing an aid to medical decision regarding brain tumor surgery.

Imaging signatures of meningioma and low-grade glioma: a diffusion tensor, magnetization transfer and quantitative longitudinal relaxation time MRI study.

Differentiation of cerebral tumor pathology currently relies on interpretation of conventional structural MRI and in some cases histology. However, more advanced MRI methods may provide further insight into the organization of cerebral tumors and have the potential to aid diagnosis. The objective of this study was to use multimodal quantitative MRI to measure the imaging signatures of meningioma and low-grade glioma (LGG). Nine adults with meningioma and 11 with LGG were identified, and underwent standard structural, quantitative longitudinal relaxation time (T1) mapping, magnetization transfer and diffusion tensor MRI. Maps of mean (〈D〉), axial (λAX) and radial (λRAD) diffusivity, fractional anisotropy (FA), magnetization transfer ratio (MTR) and T1 were generated on a voxel-by-voxel basis. Using structural and echo-planar T2-weighted MRI, manual region-of-interest segmentation of brain tumor, edema, ipsilateral and contralateral normal-appearing white matter (NAWM) was performed. Differences in imaging signatures between the different tissue types, both absolute mean values and ratios relative to contralateral NAWM, were assessed using t-tests with statistical significance set at p<0.05. For both absolute mean values and ratios relative to contralateral NAWM, there were significant differences in 〈D〉, λAX, λRAD, FA, MTR and T1 between meningioma and LGG tumor tissue, respectively. Only T1 and FA differed significantly between edematous tissue associated with the two tumor types. These results suggest that multimodal MRI biomarkers are significantly different, particularly in tumor tissue, between meningioma and LGG. By using quantitative multimodal MRI it may be possible to identify tumor pathology non-invasively.

Initial experience using awake surgery for glioma: oncological, functional, and employment outcomes in a consecutive series of 25 cases.

BACKGROUND: Awake glioma surgery aims to maximize resection to optimize prognosis while minimizing the risk of postoperative deficits. OBJECTIVE: To evaluate oncological, functional, and employment outcomes in the first cohort of patients having this type of surgery at our institution and to determine the effects of any learning curve. METHODS: All cases of awake adult (>18 years of age) glioma surgery were recorded between the introduction of this technique in 2011 until the end of 2013. Extent of tumor resection was quantified on magnetic resonance imaging and compared with the objective prediction from a resection probability map. Cognitive status was assessed preoperatively and at 3 months postoperatively. Patients were questioned about their job and capability of working before and after surgery. RESULTS: Twenty-five patients were included in the analysis. No new motor or language deficits were noted at 6 weeks after surgery. Postoperative magnetic resonance imaging showed complete resection in 11 of 13 patients with glioblastoma and >98% resection in the other 2 patients. For patients with World Health Organization grade II glioma, 3 had total, 4 had subtotal, and 3 had partial resections. Comparison between cognitive levels before and after surgery showed no change in 4 patients, improvement in some tests in 2 patients, and deterioration in some tests in 3 patients. Of 20 patients working at the time of diagnosis, 16 returned to work. CONCLUSION: These oncological and functional results of awake glioma surgery during the learning curve are comparable to results from established centers. The use and utility of resection probability maps are well demonstrated. The return to work level is high.

Human post-mortem synapse proteome integrity screening for proteomic studies of postsynaptic complexes.

BACKGROUND: Synapses are fundamental components of brain circuits and are disrupted in over 100 neurological and psychiatric diseases. The synapse proteome is physically organized into multiprotein complexes and polygenic mutations converge on postsynaptic complexes in schizophrenia, autism and intellectual disability. Directly characterising human synapses and their multiprotein complexes from post-mortem tissue is essential to understanding disease mechanisms. However, multiprotein complexes have not been directly isolated from human synapses and the feasibility of their isolation from post-mortem tissue is unknown. RESULTS: Here we establish a screening assay and criteria to identify post-mortem brain samples containing well-preserved synapse proteomes, revealing that neocortex samples are best preserved. We also develop a rapid method for the isolation of synapse proteomes from human brain, allowing large numbers of post-mortem samples to be processed in a short time frame. We perform the first purification and proteomic mass spectrometry analysis of MAGUK Associated Signalling Complexes (MASC) from neurosurgical and post-mortem tissue and find genetic evidence for their involvement in over seventy human brain diseases. CONCLUSIONS: We have demonstrated that synaptic proteome integrity can be rapidly assessed from human post-mortem brain samples prior to its analysis with sophisticated proteomic methods. We have also shown that proteomics of synapse multiprotein complexes from well preserved post-mortem tissue is possible, obtaining structures highly similar to those isolated from biopsy tissue. Finally we have shown that MASC from human synapses are involved with over seventy brain disorders. These findings should have wide application in understanding the synaptic basis of psychiatric and other mental disorders.

Clinical and methodological confounders in assessing the cerebellar cognitive affective syndrome in adult patients with posterior fossa tumours.

The cerebellar cognitive affective syndrome (CCAS) was first described by Schmahmann and Sherman as a constellation of symptoms including dysexecutive syndrome, spatial cognitive deficit, linguistic deficits and behavioural abnormalities in patients with a lesion in the cerebellum with otherwise normal brain. Neurosurgical patients with cerebellar tumours constitute one of the cohorts in which the CCAS has been described. In this paper, we present a critical review of the literature of this syndrome in neurosurgical patients. Thereafter, we present a prospective clinical study of 10 patients who underwent posterior fossa tumour resection and had a detailed post-operative neuropsychological, neuropsychiatric and neuroradiological assessment. Because our findings revealed a large number of perioperative neuroradiological confounding variables, we reviewed the neuroimaging of a further 20 patients to determine their prevalence. Our literature review revealed that study design, methodological quality and sometimes both diagnostic criteria and findings were inconsistent. The neuroimaging study (pre-operative, n = 10; post-operative, n = 10) showed very frequent neuroradiological confounding complications (e.g. hydrocephalus; brainstem compression; supratentorial lesions and post-operative subdural hygroma); the impact of such features had largely been ignored in the literature. Findings from our clinical study showed various degree of deficits in neuropsychological testing (n = 1, memory; n = 3, verbal fluency; n = 3, attention; n = 2, spatial cognition deficits; and n = 1, behavioural changes), but no patient had full-blown features of CCAS. Our study, although limited, finds no robust evidence of the CCAS following surgery. This and our literature review highlight a need for guidelines regarding study design and methodology when attempting to evaluate neurosurgical cases with regard to the potential CCAS.

The proteomic response in glioblastoma in young patients.

Increasing age is an important prognostic variable in glioblastoma (GBM). We have defined the proteomic response in GBM samples from 7 young patients (mean age 36 years) compared to peritumoural-control samples from 10 young patients (mean age 32 years). 2-Dimensional-gel-electrophoresis, image analysis, and protein identification (LC/MS) were performed. 68 proteins were significantly altered in young GBM samples with 29 proteins upregulated and 39 proteins downregulated. Over 50 proteins are described as altered in GBM for the first time. In a parallel analysis in old GBM (mean age 67 years), an excellent correlation could be demonstrated between the proteomic profile in young GBM and that in old GBM patients (r(2) = 0.95) with only 5 proteins altered significantly (p < 0.01). The proteomic response in young GBM patients highlighted alterations in protein-protein interactions in the immunoproteosome, NFkB signalling, and mitochondrial function and the same systems participated in the responses in old GBM patients.

Interactions among mitochondrial proteins altered in glioblastoma.

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥ 2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein-protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology.

Assessment of a brain-tumour-specific Patient Concerns Inventory in the neuro-oncology clinic.

PURPOSE: Brain tumour patients may struggle to express their concerns in the outpatient clinic, creating a physician-focused rather than a shared agenda. We created a simple, practical brain-tumour-specific holistic needs assessment (HNA) tool for use in the neuro-oncology outpatient clinic. METHODS: We posted the brain tumour Patient Concerns Inventory (PCI) to a consecutive sample of adult brain tumour attendees to a neuro-oncology outpatient clinic. Participants brought the completed PCI to their clinic consultation. Patients and staff provided feedback. RESULTS: Seventy seven patients were eligible and 53 participated (response rate = 68%). The PCI captured many problems absent from general cancer checklists. The five most frequent concerns were fatigue, fear of tumour coming back, memory, concentration, and low mood. Respondents used the PCI to formulate 105 specific questions, usually about the meaning of physical or psychological symptoms. Patients and staff found the PCI to be useful, and satisfaction with the instrument was high. CONCLUSIONS: This study demonstrates the clinical utility of the brain tumour PCI in a neuro-oncology clinic. The combination of a brain-tumour-specific concerns checklist and an intervention to focus patient agenda creates a simple and efficient HNA tool.

A test-retest fMRI dataset for motor, language and spatial attention functions.

BACKGROUND: Since its inception over twenty years ago, functional magnetic resonance imaging (fMRI) has been used in numerous studies probing neural underpinnings of human cognition. However, the between session variance of many tasks used in fMRI remains understudied. Such information is especially important in context of clinical applications. A test-retest dataset was acquired to validate fMRI tasks used in pre-surgical planning. In particular, five task-related fMRI time series (finger, foot and lip movement, overt verb generation, covert verb generation, overt word repetition, and landmark tasks) were used to investigate which protocols gave reliable single-subject results. Ten healthy participants in their fifties were scanned twice using an identical protocol 2-3 days apart. In addition to the fMRI sessions, high-angular resolution diffusion tensor MRI (DTI), and high-resolution 3D T1-weighted volume scans were acquired. FINDINGS: Reliability analyses of fMRI data showed that the motor and language tasks were reliable at the subject level while the landmark task was not, despite all paradigms showing expected activations at the group level. In addition, differences in reliability were found to be mostly related to the tasks themselves while task-by-motion interaction was the major confounding factor. CONCLUSIONS: Together, this dataset provides a unique opportunity to investigate the reliability of different fMRI tasks, as well as methods and algorithms used to analyze, de-noise and combine fMRI, DTI and structural T1-weighted volume data.

Tolerance of awake surgery for glioma: a prospective European Low Grade Glioma Network multicenter study.

BACKGROUND: Gross total removal of glioma is limited by proximity to eloquent brain. Awake surgery allows for intraoperative monitoring to safely identify eloquent regions. However, data on adverse psychological effects induced in these patients is limited. OBJECTIVE: This study explored patients' perception of awake surgery for glioma, with special focus on intraoperative pain and anxiety. METHODS: This study was conducted at five neurosurgical centers within the European Low Grade Glioma Network. Patients underwent awake surgery for glioma according to the protocol of the individual center. Pain and discomfort were measured during the awake phase. Postoperatively, patients answered a questionnaire on aspects of their operation. RESULTS: One hundred five patients were enrolled. Pain levels on a 10-cm visual analogue scale were 1.3 cm at the beginning, 1.9 cm the middle, and 2.1 cm at the end of awake phase. Levels of anxiety were 2.2 cm, 2.5 cm and 2.6 cm, respectively. Women and patients younger than 60 years exhibited highest mean anxiety levels. The patient questionnaire revealed that the majority of patients feel comfortable with the procedure. Discomfort resulted from head fixation or positioning on the operating table. CONCLUSIONS: We demonstrate that awake surgery is well tolerated, as neither intraoperative nor postoperative assessment revealed major disadvantages. Concerning practical lessons learned from this study, we emphasize the importance of minimizing pain and preparing patients thoroughly to reduce anxiety and maximize cooperation. Awake surgery is an excellent treatment modality for brain tumors with very positive perception by patients.

Single subject fMRI test-retest reliability metrics and confounding factors.

While the fMRI test-retest reliability has been mainly investigated from the point of view of group level studies, here we present analyses and results for single-subject test-retest reliability. One important aspect of group level reliability is that not only does it depend on between-session variance (test-retest), but also on between-subject variance. This has partly led to a debate regarding which reliability metric to use and how different sources of noise contribute to between-session variance. Focusing on single subject reliability allows considering between-session only. In this study, we measured test-retest reliability in four behavioural tasks (motor mapping, covert verb generation, overt word repetition, and a landmark identification task) to ensure generalisation of the results and at three levels of data processing (time-series correlation, t value variance, and overlap of thresholded maps) to understand how each step influences the other and how confounding factors influence reliability at each of these steps. The contributions of confounding factors (scanner noise, subject motion, and coregistration) were investigated using multiple regression and relative importance analyses at each step. Finally, to achieve a fuller picture of what constitutes a reliable task, we introduced a bootstrap technique of within- vs. between-subject variance. Our results show that (i) scanner noise and coregistration errors have little contribution to between-session variance (ii) subject motion (especially correlated with the stimuli) can have detrimental effects on reliability (iii) different tasks lead to different reliability results. This suggests that between-session variance in fMRI is mostly caused by the variability of underlying cognitive processes and motion correlated with the stimuli rather than technical limitations of data processing.

Overcoming fear and anxiety during awake resection of brain tumours: family support can be pivotal to a successful outcome.

Patient anxiety and fear about an awake craniotomy can affect the patient's choice about having an operation despite comprehensive pre-operative counselling. We report three cases in which a family member came into theatre during the procedure to support the patient during surgery. All three cases, which involved intra-operative cortical and subcortical stimulations and intra-operative patient testing, were successfully completed with major tumour resections and no post-operative complications. We suggest that family support should be considered in patients who have extreme fear and anxiety about awake surgery.

NICE guidance on the use of carmustine wafers in high grade gliomas: a national study on variation in practice.

BACKGROUND: Multidisciplinary team (MDT) working in oncology aims to improve outcomes for patients with cancer. One role is to ensure the implementation of best practice and National Institute for Health and Clinical Excellence (NICE) guidance. In this study, we have assessed the role of MDT in implementing the TA121 appraisal of the use of carmustine wafers in high grade gliomas. METHODS: 296 patients with high-grade glioma suitable for maximal resection were recruited from 17 Neurosurgical Centres. The number of patients treated with carmustine wafers and reasons for not using this were recorded. Complications at 48 hours post-operatively and at 6 weeks post-radiotherapy were recorded. RESULTS: 94/296 (32%) of suitable patients received carmustine wafers. In 55% of cases carmustine was not used due to either surgeon preference or a lack of an MDT decision. There was no increased complication rate with carmustine use at either 48 hours post-surgery or at 6 weeks post radiotherapy. Use of carmustine wafers did not decrease access to and use of chemoradiotherapy. CONCLUSIONS: One third of patients suitable for carmustine wafers received them. Their use was neither associated with more frequent complications, nor decreased use of chemoradiotherapy. Implementation of NICE TA121 Guidance is extremely variable in different MDTs across the United Kingdom.

A propensity-matched comparison of survival after lung resection in patients with a high versus low body mass index.

OBJECTIVES: An inverse relationship between body mass index (BMI) and the risk of lung cancer has been reported in several studies. In this study, we aimed to assess whether BMI can affect survival after lung resection for cancer. METHODS: We reviewed patient data for a 10-year period; 337 patients with BMI ≥ 30 who underwent lung resection for non-small cell lung cancer were identified. This group of patients was matched at a ratio of 1:1 to a group with BMI <30 and with similar characteristics such as sex, age, lung function test, history of smoking, diabetes, peripheral vascular disease, stroke, myocardial infarction, chronic obstructive pulmonary disease (COPD), procedure type, histology and stage of tumour. We also used the Kaplan-Meier survival curves before and after matching for the above mentioned patient characteristics. RESULTS: Before adjusting for the preoperative and operative characteristics, despite more history of diabetes, hypertension and renal impairment in patients with BMI ≥ 30 compared to those with BMI <30 (BMI = 18.5-30 and < 8.5), the survival rate was found to be significantly higher when analysed univariately (P = 0.02). This difference remained significant after adjusting for all the characteristics, suggesting a significantly higher survival rate in the group with BMI ≥ 30 (P = 0.04). CONCLUSIONS: Unlike in breast cancer, a high BMI in lung cancer patients after resection has protective effects. This may be due to the better nutritional status of the patient, a less aggressive cancer type that has not resulted in weight loss at the time of presentation or it may be due to certain hormones released from the adipose tissue. BMI can be a predictor of outcome after lung resection in cancer patients.