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The Nuffield Department of Surgical Sciences is the academic department of surgery at the University of Oxford, and hosts a multidisciplinary team of senior clinical academic surgeons, senior scientists, junior clinicians and scientists in training.
Thalamic deep brain stimulation for post-traumatic neuropathic limb pain: Efficacy at five years' follow-up and effective volume of activated brain tissue.
Chronic neuropathic pain affects 7%-10% of the population. Deep brain stimulation (DBS) has shown variable but promising results in its treatment. This study prospectively assessed the long-term effectiveness of DBS in a series of patients with chronic neuropathic pain, correlating clinical results with neuroimaging. Sixteen patients received 5 years' post-surgical follow-up in a single center. Six had phantom limb pain after amputation and 10 had deafferentation pain after traumatic brachial plexus injury. Patient-reported outcome measures were completed before and after surgery, using VAS, UWNPS, BPI and SF-36 scores. Neuroimaging evaluated electrode location and effective volumes of activated tissue (VAT). Two subgroups were created based on the percentage of VAT superimposed upon the ventroposterolateral thalamic nucleus (eVAT), and clinical outcomes were compared. Analgesic effect was assessed at 5 years and compared to preoperative pain, with an improvement on VAS of 76.4% (p=0.0001), on UW-NPS of 35.2% (p=0.3582), on BPI of 65.1% (p=0.0505) and on SF-36 of 5% (p=0.7406). Eight patients with higher eVAT showed improvement on VAS of 67.5% (p=0.0017) while the remaining patients, with lower eVAT, improved by 50.6% (p=0.03607). DBS remained effective in improving chronic neuropathic pain after 5 years. While VPL-targeting contributes to success, analgesia is also obtained by stimulating surrounding posterior ventrobasal thalamic structures and related spinothalamocortical tracts.
Group II Metabotropic Glutamate Receptors Mediate Presynaptic Inhibition of Excitatory Transmission in Pyramidal Neurons of the Human Cerebral Cortex.
Group II metabotropic glutamate receptor (mGluR) ligands are potential novel drugs for neurological and psychiatric disorders, but little is known about the effects of these compounds at synapses of the human cerebral cortex. Investigating the effects of neuropsychiatric drugs in human brain tissue with preserved synaptic circuits might accelerate the development of more potent and selective pharmacological treatments. We have studied the effects of group II mGluR activation on excitatory synaptic transmission recorded from pyramidal neurons of cortical layers 2-3 in acute slices derived from surgically removed cortical tissue of people with epilepsy or tumors. The application of a selective group II mGluR agonist, LY354740 (0.1-1 μM) inhibited the amplitude and frequency of action potential-dependent spontaneous excitatory postsynaptic currents (sEPSCs). This effect was prevented by the application of a group II/III mGluR antagonist, CPPG (0.1 mM). Furthermore, LY354740 inhibited the frequency, but not the amplitude, of action potential-independent miniature EPSCs (mEPSCs) recorded in pyramidal neurons. Finally, LY354740 did slightly reduce cells' input resistance without altering the holding current of the neurons recorded in voltage clamp at -90 mV. Our results suggest that group II mGluRs are mainly auto-receptors that inhibit the release of glutamate onto pyramidal neurons in layers 2-3 in the human cerebral cortex, thereby regulating network excitability. We have demonstrated the effect of a group II mGluR ligand at human cortical synapses, revealing mechanisms by which these drugs could exert pro-cognitive effects and treat human neuropsychiatric disorders.
No turning back: a long-term retrospective analysis of urgent magnetic resonance imaging (MRI) performed for suspected cauda equina compression in a tertiary referral centre
AIM: Cauda equina syndrome is a rare but potentially serious condition for which diagnosis is time-critical for the best outcomes. Magnetic resonance imaging (MRI) is the imaging modality of choice, but the diagnostic pathway is challenging as availability of 24/7 urgent MRI is mostly limited to tertiary centres. We present a 13-year experience at one such tertiary centre. MATERIALS AND METHODS: All lumbar spine MRIs performed for suspected cauda equina between 2011 and 2023 were identified retrospectively from trust-wide information technology (IT) systems. Data including time from request to scan acquisition and reporting times were analysed using automated methods with manual validation. RESULTS: At our institution, there has been a 10-fold increase in demand for MRI to exclude cauda equina compression over the last decade. In recent years, the mean duration from request to MRI acquisition was within the 4-hour national target in approximately 90% of cases, and time from MRI acquisition to first verified report met the 1-hour national target in just over half of cases (51.1% in 2023). In 2023, 90.0% of reports were verified within 4 hours and 77.5 % within 2 hours, satisfying locally defined standards. Since 2012, 377 patients with clinical suspicion of cauda equina syndrome and positive MRI proceeded to spinal surgery within a week. The mean 5.1% operative rate between 2012 and 2023 corresponds well to previous literature. CONCLUSION: There is a rising demand for urgent MRI to exclude cauda equina compression with consequent logistical and financial considerations required to meet new national guidance on scan acquisition and reporting targets.
Dynamic changes in rhythmic and arrhythmic neural signatures in the subthalamic nucleus induced by anaesthesia and tracheal intubation.
BACKGROUND: Subcortical structures, including the basal ganglia, have been proposed to be crucial for arousal, consciousness, and behavioural responsiveness. How the basal ganglia contribute to the loss and recovery of consciousness during anaesthesia has, however, not yet been well characterised. METHODS: Twelve patients with advanced Parkinson's disease, who were undergoing deep brain stimulation (DBS) electrode implantation in the subthalamic nucleus (STN), were included in this study. Local field potentials (LFPs) were recorded from the DBS electrodes and EEG was recorded from the scalp during induction of general anaesthesia (with propofol and sufentanil) and during tracheal intubation. Neural signatures of loss of consciousness and of the expected arousal during intubation were sought in the STN and EEG recordings. RESULTS: Propofol-sufentanil anaesthesia resulted in power increases in delta, theta, and alpha frequencies, and broadband power decreases in higher frequencies in both STN and frontal cortical areas. This was accompanied by increased STN-frontal cortical coherence only in the alpha frequency band (119 [68]%; P=0.0049). We observed temporal activity changes in STN after tracheal intubation, including power increases in high-beta (22-40 Hz) frequency (98 [123]%; P=0.0064) and changes in the power-law exponent in the power spectra at lower frequencies (2-80 Hz), which were not observed in the frontal cortex. During anaesthesia, the dynamic changes in the high-gamma power in STN LFPs correlated with the power-law exponent in the power spectra at lower frequencies (2-80 Hz). CONCLUSIONS: Apart from similar activity changes in both STN and cortex associated with anaesthesia-induced unresponsiveness, we observed specific neuronal activity changes in the STN in response to the anaesthesia and tracheal intubation. We also show that the power-law exponent in the power spectra in the STN was modulated by tracheal intubation in anaesthesia. Our results support the hypothesis that subcortical nuclei may play an important role in the loss and return of responsiveness.
Rechargeable vs. nonrechargeable internal pulse generators in the management of dystonia.
OBJECTIVE: To test if deep brain stimulation (DBS) treatment of dystonia was similar in patients before and after implantation of rechargeable internal pulse generators (IPGs). MATERIALS AND METHODS: The Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) severity and disability scores were compared in patients before DBS insertion, 24 months after DBS insertion with a nonrechargeable IPG, and after implantation of a rechargeable IPG. RESULTS: No significant differences were observed between dystonia control in patients before and after implantation of a rechargeable IPG. CONCLUSIONS: Rechargeable IPGs should be the IPGs of choice for dystonic patients receiving DBS as IPGs offer similar treatment efficacy to nonrechargeable IPGs with advantages in terms of costs and reductions in reimplantation frequency.
Everything to gain: Sir Hugh Cairns' treatment of central nervous system infection at Oxford and abroad.
Antibiotics have revolutionized survival from central nervous system (CNS) infections. Sixty years after the death of Sir Hugh Cairns, we present archive material of historical interest from the Radcliffe Infirmary in Oxford from the time of his first trials of penicillin for CNS infection. We discuss Cairns' important wartime and subsequent contributions to antibiosis in CNS infection and include drawings by Audrey Arnott illustrating the surgical techniques used to treat abscesses at the time.
Deep brain stimulation in multiple system atrophy mimicking idiopathic Parkinson's disease.
Deep brain stimulation (DBS) is approved for idiopathic Parkinson's disease (IPD) but has a poor evidence base in Parkinson-plus syndromes such as multiple system atrophy (MSA). We describe the clinical and neuropathological findings in a man who was initially diagnosed with IPD, in whom DBS was unsuccessful, and in whom MSA was unexpectedly diagnosed at a subsequent autopsy. This case report highlights that DBS is often unsuccessful in MSA and also demonstrates that MSA can masquerade as IPD, which may explain treatment failure in a small group of patients apparently suffering from Parkinson's disease. Additionally, it also presents a case with an unusually long duration of disease prior to death, comparable only to a handful of other cases in the literature.
Dorsal Anterior Cingulate Cortices Differentially Lateralize Prediction Errors and Outcome Valence in a Decision-Making Task.
The dorsal anterior cingulate cortex (dACC) is proposed to facilitate learning by signaling mismatches between the expected outcome of decisions and the actual outcomes in the form of prediction errors. The dACC is also proposed to discriminate outcome valence-whether a result has positive (either expected or desirable) or negative (either unexpected or undesirable) value. However, direct electrophysiological recordings from human dACC to validate these separate, but integrated, dimensions have not been previously performed. We hypothesized that local field potentials (LFPs) would reveal changes in the dACC related to prediction error and valence and used the unique opportunity offered by deep brain stimulation (DBS) surgery in the dACC of three human subjects to test this hypothesis. We used a cognitive task that involved the presentation of object pairs, a motor response, and audiovisual feedback to guide future object selection choices. The dACC displayed distinctly lateralized theta frequency (3-8 Hz) event-related potential responses-the left hemisphere dACC signaled outcome valence and prediction errors while the right hemisphere dACC was involved in prediction formation. Multivariate analyses provided evidence that the human dACC response to decision outcomes reflects two spatiotemporally distinct early and late systems that are consistent with both our lateralized electrophysiological results and the involvement of the theta frequency oscillatory activity in dACC cognitive processing. Further findings suggested that dACC does not respond to other phases of action-outcome-feedback tasks such as the motor response which supports the notion that dACC primarily signals information that is crucial for behavioral monitoring and not for motor control.
Direct neurophysiological evidence for a role of the human anterior cingulate cortex in central command.
INTRODUCTION: The role of the anterior cingulate cortex (ACC) is still controversial. The ACC has been implicated in such diverse functions as cognition, arousal and emotion in addition to motor and autonomic control. Therefore the ACC is the ideal candidate to orchestrate cardiovascular performance in anticipation of perceived skeletal activity. The aim of this experiment was to investigate whether the ACC forms part of the neural network of central command whereby cardiovascular performance is governed by a top-down mechanism. METHODS & RESULTS: Direct local field potential (LFP) recordings were made using intraparenchymal electrodes in six human ACC's to measure changes in neuronal activity during performance of a motor task in which anticipation of exercise was uncoupled from skeletal activity itself. Parallel cardiovascular arousal was indexed by electrocardiographic changes in heart rate. During anticipation of exercise, ACC LFP power within the 25-60 Hz frequency band increased significantly by 21% compared to rest (from 62.7 μV2/Hz (±SE 4.94) to 76.0μV2/Hz (±SE 7.24); p = 0.004). This 25-60 Hz activity increase correlated with a simultaneous heart rate increase during anticipation (Pearson's r = 0.417, p = 0.016). CONCLUSIONS/SIGNIFICANCE: We provide the first invasive electrophysiological evidence to support the role of the ACC in both motor preparation and the top-down control of cardiovascular function in exercise. This further implicates the ACC in the body's response to the outside world and its possible involvement in such extreme responses as emotional syncope and hyperventilation. In addition we describe the frequency at which the neuronal ACC populations perform these tasks in the human.
Role of diffusion-weighted imaging in monitoring treatment response following high-intensity focused ultrasound ablation of recurrent sacral chordoma.
Chordoma is the most common malignant tumor of the sacrum and is associated with significant neurologic morbidity. Local recurrence is very common, and the long-term prognosis is poor. High-intensity focused ultrasound (HIFU) is a noninvasive and nonionising ablative therapy that has been successful in treating other tumor types and is being evaluated as a new therapy for sacral chordoma. Contrast-enhanced magnetic resonance imaging is typically used to evaluate tumor perfusion following HIFU; however, its utility is limited in poorly perfused tumors. Diffusion-weighted imaging (DWI) provides tissue contrast based on differences in the diffusion of extracellular water without using gadolinium-based contrast agents. We present novel DWI findings following a planned partial HIFU ablation of a large sacral chordoma which had recurred after radiotherapy. Following HIFU, the treated tumor volume demonstrated loss of restriction on DWI correlating with photopenia on positron emission tomography. This suggests successful ablation and tumor necrosis. This novel finding may provide guidance for sequence selection when evaluating HIFU therapy for sacral chordoma and other tumor types for which contrast-enhanced magnetic resonance imaging may have limited utility.
Effect of a Laparoscopic Donor Nephrectomy in Healthy Living Kidney Donors on the Acute Phase Response Using Either Propofol or Sevoflurane Anesthesia
Surgical trauma elicits a complex inflammatory stress response, contributing to postoperative morbidity and recovery variability. This response is influenced by patient-specific factors and surgical and anesthetic techniques. To isolate the impact of anesthesia on the acute phase response, we investigated plasma proteomic changes in a uniquely homogeneous cohort of healthy, living kidney donors (n = 36; propofol = 19; sevoflurane = 17) undergoing laparoscopic donor nephrectomy. Proteomic profiling of plasma samples collected preoperatively and at 2 and 24 h postoperatively revealed 633 quantifiable proteins, of which 22 showed significant perioperative expression changes. Eight proteins exhibited over two-fold increases, primarily related to the acute phase response (CRP, SAA1, SAA2, LBP), tissue repair (FGL1, A2GL), and anti-inflammatory regulation (AACT). These changes were largely independent of anesthetic type, though SAA2 and MAN1A1 showed anesthetic-specific expression. The upregulation of these proteins implicates the activation of immune pathways involved in host defense, tissue remodeling, and inflammation resolution. Our findings provide a molecular reference for the surgical stress response in healthy individuals and highlight candidate biomarkers for predicting and managing postoperative outcomes. Understanding these pathways may support the development of strategies to mitigate surgical stress and enhance recovery, particularly in vulnerable patient populations.
Size Matters: Micro v. Nanobubbles in Ultrasound Imaging and Therapy Dataset
This data was created using a mix of theoretical modelling, computational analysis of images, sizing instruments and ultrasound data. Full details are in the associated paper.
Associations Between Lactate Thresholds and 2000 m Rowing Ergometer Performance: Implications for Prediction-A Systematic Review.
BACKGROUND: Various exercise thresholds have been evaluated to predict athlete performance. However, a systematic review of the literature assessing the association between lactate-based exercise thresholds and 2000 m rowing ergometer performance is still lacking. These may have utility in the prediction of 2000 m rowing ergometer performance due to the close relationship between metabolic parameters and development of endurance capacity. The aim of the present study is to review and assess the extent, quality, and reliability of lactate-based exercise testing and methodologies in their association with 2000 m rowing ergometer performance, and to discuss the potential implications for performance prediction. METHODS: The systematic review was performed following PRISMA 2020 guidelines. The databases searched were EMBASE, MEDLINE and SPORTDiscus. The initial search took place in July 2022, with an update search performed in September 2023, and again in August 2024. Studies which reported a lactate test and its correlation to 2000 m ergometer performance were included. No meta-analysis was performed. RESULTS: Twenty-four studies comprising 797 athletes (513 male, 257 female, 27 not stated) met the eligibility criteria for inclusion in the review. The most commonly used testing protocol involved the use of incremental step-tests. A range of exercise intensity parameters, lactate-based exercise thresholds and interpretation methodologies were employed. Of these, the power or velocity at a blood lactate concentration of 4 mmol l-1 was the most common test, with correlation coefficients ranging from 0.53 to 0.96 suggesting that 28-92% of the variance in rowing performance can be explained by this metric. Six studies that rated as GOOD on the risk of bias assessment found very strong correlations > 0.85 (p
The 6 Minute Walk Test as a predictor of mortality in idiopathic pulmonary fibrosis: A systematic review.
BACKGROUND: The 6-min walk test (6MWT) is frequently used in pulmonary fibrosis (PF) research. It evaluates an individual's sub-maximal exercise performance by measuring the distance they walk and their vital signs across 6 min. In research studies, the 6-min walk distance (6MWD) is often used as a surrogate marker for disease progression. The aim of this study was to systematically assess the association between 6MWT parameters and mortality in PF. METHODS: MEDLINE, EMBASE, CINAHL, and CENTRAL databases were searched for studies reporting mortality and 6MWD in patients with PF. Study quality was assessed using a modified Newcastle-Ottawa Scale. Studies were included if they reported associations between the 6MWT in pulmonary fibrosis and mortality. Results were presented as a narrative synthesis. RESULTS: 2312 studies were identified, 22 studies met the pre-defined inclusion criteria, comprising 5940 Idiopathic PF patients. Baseline 6MWD was found to be loosely associated with mortality (Ranges: univariate HR 0.89-4.72, multivariate HR 0.96-2.65), while a decrease in 6MWD across 24-weeks was correlated with a higher risk of mortality (Ranges: univariate HR 2.25-4.81, multivariate HR 1.72-4.3). DISCUSSION: This review found that a low baseline 6MWD, and a 6-month decrease in 6MWD were strongly correlated with increased mortality in Idiopathic PF patients. As the 6MWT is a safe, easy-to-conduct test, it is appropriate for use as a marker of patient prognosis, in both clinical and research settings. OPEN SCIENCE FRAMEWORK PROTOCOL REGISTRATION: DOI 10.17605/OSF.IO/3D7BV.