Introduction
Despite evidence of correspondence with intraoperative stimulation, there remains limited data on MRI diffusion tractography (DT)’s sensitivity to predict morbidity after neurosurgical ...oncology treatment. Our aims were: (1) evaluate DT against subcortical stimulation mapping and performance changes during and after awake neurosurgery; (2) evaluate utility of early post-operative DT to predict recovery from post-surgical deficits.
Methods
We retrospectively reviewed our first 100 awake neurosurgery procedures using DT- neuronavigation. Intra-operative stimulation and performance outcomes were assessed to classify DT predictions for sensitivity and specificity calculations. Post-operative DT data, available in 51 patients, were inspected for tract damage.
Results
91 adult brain tumor patients (mean 49.2 years, 43 women) underwent 100 awake surgeries with subcortical stimulation between 2014 and 2019. Sensitivity and specificity of pre-operative DT predictions were 92.2% and 69.2%, varying among tracts. Post-operative deficits occurred after 41 procedures (39%), but were prolonged (> 3 months) in only 4 patients (4%). Post-operative DT in general confirmed surgical preservation of tracts. Post-operative DT anticipated complete recovery in a patient with supplementary motor area syndrome, and indicated infarct-related damage to corticospinal fibers associated with delayed, partial recovery in a second patient.
Conclusions
Pre-operative DT provided very accurate predictions of the spatial location of tracts in relation to a tumor. As expected, however, the presence of a tract did not inform its functional status, resulting in variable DT specificity among individual tracts. While prolonged deficits were rare, DT in the immediate post-operative period offered additional potential to monitor neurological deficits and anticipate recovery potential.
Gait disturbance and postural instability are some the most disabling symptoms of idiopathic Parkinson's disease and in late stage disease can be resistant to both medical and surgical therapies. We ...implanted bilateral deep brain stimulation electrodes into the pedunculopontine nucleus in two patients with advanced Parkinson's disease. We demonstrate for the first time that low frequency (20-25 Hz) stimulation of this nucleus significantly improves gait dysfunction and postural instability in both the 'on' and 'off' medication states. Their combined total Unified Parkinson's Disease Rating Scale score improved by 53% and motor score by 57%. No procedure or stimulation-related complications were observed. If these findings are replicated in a larger number of patients, pedunculopontine nucleus stimulation may provide the means to alleviate these disabling and otherwise treatment-resistant symptoms of advanced Parkinson's disease.
Better understanding of breathlessness perception addresses an unmet clinical need for more effective treatments for intractable dyspnoea, a prevalent symptom of multiple medical conditions. The ...insular-cortex is predominantly activated in brain-imaging studies of dyspnoea, but its precise role remains unclear. We measured experimentally-induced hypercapnic air-hunger in three insular-glioma patients before and after surgical resection. Tests involved one-minute increments in inspired CO
, raising end-tidal
CO
to 7.5 mmHg above baseline (38.5 ± 5.7 mmHg), whilst ventilation was constrained (10.7 ± 2.3 L/min). Patients rated air-hunger on a visual analogue scale (VAS). Patients had lower stimulus-response (2.8 ± 2 vs. 11 ± 4 %VAS/mmHg;
= 0.004), but similar threshold (40.5 ± 3.9 vs. 43.2 ± 5.1 mmHg), compared to healthy individuals. Volunteered comments implicated diminished affective valence. After surgical resection; sensitivity increased in one patient, decreased in another, and other was unable to tolerate the ventilatory limit before any increase in inspired CO
.We suggest that functional insular-cortex is essential to register breathlessness unpleasantness and could be targeted with neuromodulation in chronically-breathless patients. Neurological patients with insula involvement should be monitored for blunted breathlessness to inform clinical management.
We have shown previously that intraparenchymal infusion of glial cell line–derived neurotrophic factor (GDNF) continuously into the posterior putamen in five Parkinson's disease patients is safe and ...may represent a new treatment option. Here, we report a continuation of this phase I study. After 2 years of continual GDNF infusion, there were no serious clinical side effects and no significant detrimental effects on cognition. Patients showed a 57% and 63% improvement in their off‐medication motor and activities of daily living subscores of the Unified Parkinson's Disease Rating Scale, respectively, and health‐related quality‐of‐life measures (Parkinson's Disease Questionnaire–39 and Short Form–36) showed general improvement over time. Ann Neurol 2005;57:298–302
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.
Introduction5-aminolevulinic acid (5-ALA) is a proagent developed for fluorescent-guided surgery for high-grade glioma patients associated with a significant increase in resection conferring ...survival. 5-ALA was shown to penetrate the blood–brain barrier accumulating in malignant glioma cells with high selectivity, sensitivity and positive predictive value. However, those have yet to be explored aiding diagnosis for tumours of the central nervous system (CNS) other than high-grade gliomas (HGG). No up-to-date systematic review exists reporting the major surgical outcomes and diagnostic accuracy. We sought to conduct a systematic review of the literature summarising surgical outcomes, evaluate the quality of diagnostic accuracy reported in the literature and qualitatively assess the evidence to inform future studies.Methods and analysisWe will search electronic databases (Medline, Embase) with subsequent interrogation of references lists of articles reporting the use of 5-ALA for brain tumours other than high-grade glioma adult patients, which also report the extent of resection and/or survival. Prospective and retrospective cohort and case–control studies with more than five patients will be included. Two independent reviewers will screen the abstracts and full articles, with a third reviewer resolving any conflicts. The data will be extracted in a standardised template and outcomes will be reported using descriptive statists. The quality of non-randomised studies will be appraised.Ethics and disseminationThe study will summarise the available evidence on the effect of the clinical utility of 5-ALA in achieving resection and improving survival and its diagnostic accuracy for tumours of the CNS other than HGG. The data will be presented nationally and internationally and the manuscript will be published in a peer-reviewed journal. No ethical approvals were needed. The aim is to inform prospective studies minimising reporting bias allowing for more reliable, reproducible and generalisable results. The study has been registered in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.PROSPERO registration numberCRD42021260542.
Objective To report a minimally invasive, nontubular endoscopic technique to resect intraparenchymal brain tumors and assess the feasibility, safety, and surgical resection margins achievable by this ...novel technique. Methods Over a 21-month period, 48 patients underwent 50 consecutive endoscopic intraparenchymal tumor resections. Data on surgical morbidity and mortality and length of stay were collected prospectively. The percentage of surgical resection and residual tumor volumes were calculated using preoperative and postoperative volume computed tomography or magnetic resonance imaging. All tumors were resected through a 2-cm minicraniotomy using a high-definition rigid endoscope with a 30-degree viewing angle. Bimanual resection was performed using standard microsurgical technique. Results Mean patient age was 53 years. There were 42 supratentorial (19 frontal, 17 temporal, 3 occipital, 1 parietal, and 2 parafalcine) tumors and 8 infratentorial tumors. Mean tumor volume was 41 cm3 . There were 12 metastases, 24 glioblastomas, 4 World Health Organization grade III gliomas, 5 World Health Organization grade I–II gliomas, 3 meningiomas, and 2 hemangioblastomas. On volumetric analysis, the overall mean percent resection was 96%. In 70% of cases, >95% resection was achieved; total resection was achieved in 48% of cases. At 30 days postoperatively, there was 1 new postoperative neurologic deficit; there were no deaths during this period. Conclusions Our experience demonstrates that resection of intraparenchymal tumors using a minimally invasive endoscopic technique is technically feasible and safe, achieves good tumor resection margins, and has some potential advantages over a traditional microscopic technique.
•FMRI connectivity fingerprints represent patient-unique language networks.•Fingerprints can be statistically tested to detect reorganisation in individuals.•Connectivity fingerprints track ...surgery-related adaptations in individual patients.•Network-level changes appear related to presence of language symptoms.
Large individual differences in how brain networks respond to treatment hinder efforts to personalise treatment in neurological conditions. We used a brain network fingerprinting approach to longitudinally track re-organisation of complementary phonological and semantic language networks in 19 patients before and after brain-tumour surgery. Patient task fingerprints were individually compared to normal networks established in 17 healthy controls. Additionally, pre- and post-operative patient fingerprints were directly compared to assess longitudinal network adaptations. We found that task networks remained stable over time in healthy controls, whereas treatment induced reorganisation in 47.4% of patient fluency networks and 15.8% of semantic networks. How networks adapted after surgery was highly unique; a subset of patients (10%) showed ‘normalisation’ while others (21%) developed newly atypical networks after treatment. The strongest predictor of adaptation of the fluency network was the presence of clinically reported language symptoms. Our findings indicate a tight coupling between processes disrupting performance and neural network adaptation, the patterns of which appear to be both task- and individually-unique. We propose that connectivity fingerprinting offers potential as a clinical marker to track adaptation of specific functional networks across treatment interventions over time.
Pressures on healthcare systems due to COVID-19 has impacted patients without COVID-19 with surgery disproportionally affected. This study aims to understand the impact on the initial management of ...patients with brain tumours by measuring changes to normal multidisciplinary team (MDT) decision making.
A prospective survey performed in UK neurosurgical units performed from 23 March 2020 until 24 April 2020.
Regional neurosurgical units outside London (as the pandemic was more advanced at time of study).
Representatives from all units were invited to collect data on new patients discussed at their MDT meetings during the study period. Each unit decided if management decision for each patient had changed due to COVID-19.
Primary outcome measures included number of patients where the decision to undergo surgery changed compared with standard management usually offered by that MDT. Secondary outcome measures included changes in surgical extent, numbers referred to MDT, number of patients denied surgery not receiving any treatment and reasons for any variation across the UK.
18 units (75%) provided information from 80 MDT meetings that discussed 1221 patients. 10.7% of patients had their management changed-the majority (68%) did not undergo surgery and more than half of this group not undergoing surgery had no active treatment. There was marked variation across the UK (0%-28% change in management). Units that did not change management could maintain capacity with dedicated oncology lists. Low volume units were less affected.
COVID-19 has had an impact on patients requiring surgery for malignant brain tumours, with patients receiving different treatments-most commonly not receiving surgery or any treatment at all. The variations show dedicated cancer operating lists may mitigate these pressures.
This study was registered with the Royal College of Surgeons of England's COVID-19 Research Group (https://www.rcseng.ac.uk/coronavirus/rcs-covid-research-group/).
IntroductionSurgery 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 analysisThis 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 disseminationThe 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 numberISRCTN38834571.
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