A pilot clinical study to estimate intracranial pressure utilising cerebral photoplethysmograms in traumatic brain injury patients.

PURPOSE: In this research, a non-invasive intracranial pressure (nICP) optical sensor was developed and evaluated in a clinical pilot study. The technology relied on infrared light to probe brain tissue, using photodetectors to capture backscattered light modulated by vascular pulsations within the brain's vascular tissue. The underlying hypothesis was that changes in extramural arterial pressure could affect the morphology of recorded optical signals (photoplethysmograms, or PPGs), and analysing these signals with a custom algorithm could enable the non-invasive calculation of intracranial pressure (nICP). METHODS: This pilot study was the first to evaluate the nICP probe alongside invasive ICP monitoring as a gold standard. nICP monitoring occurred in 40 patients undergoing invasive ICP monitoring, with data randomly split for machine learning. Quality PPG signals were extracted and analysed for time-based features. The study employed Bland-Altman analysis and ROC curve calculations to assess nICP accuracy compared to invasive ICP data. RESULTS: Successful acquisition of cerebral PPG signals from traumatic brain injury (TBI) patients allowed for the development of a bagging tree model to estimate nICP non-invasively. The nICP estimation exhibited 95% limits of agreement of 3.8 mmHg with minimal bias and a correlation of 0.8254 with invasive ICP monitoring. ROC curve analysis showed strong diagnostic capability with 80% sensitivity and 89% specificity. CONCLUSION: The clinical evaluation of this innovative optical nICP sensor revealed its ability to estimate ICP non-invasively with acceptable and clinically useful accuracy. This breakthrough opens the door to further technological refinement and larger-scale clinical studies in the future. TRIAL REGISTRATION: NCT05632302, 11th November 2022, retrospectively registered.

Serum amyloid P component accumulates and persists in neurones following traumatic brain injury.

The mechanisms underlying neurodegenerative sequelae of traumatic brain injury (TBI) are poorly understood. The normal plasma protein, serum amyloid P component (SAP), which is normally rigorously excluded from the brain, is directly neurocytotoxic for cerebral neurones and also binds to Aß amyloid fibrils and neurofibrillary tangles, promoting formation and persistence of Aß fibrils. Increased brain exposure to SAP is common to many risk factors for dementia, including TBI, and dementia at death in the elderly is significantly associated with neocortical SAP content. Here, in 18 of 30 severe TBI cases, we report immunohistochemical staining for SAP in contused brain tissue with blood-brain barrier disruption. The SAP was localized to neurofilaments in a subset of neurones and their processes, particularly damaged axons and cell bodies, and was present regardless of the time after injury. No SAP was detected on astrocytes, microglia, cerebral capillaries or serotoninergic neurones and was absent from undamaged brain. C-reactive protein, the control plasma protein most closely similar to SAP, was only detected within capillary lumina. The appearance of neurocytotoxic SAP in the brain after TBI, and its persistent, selective deposition in cerebral neurones, are consistent with a potential contribution to subsequent neurodegeneration.

Feasibility of comparing medical management and surgery (with neurosurgery or stereotactic radiosurgery) with medical management alone in people with symptomatic brain cavernoma - protocol for the Cavernomas: A Randomised Effectiveness (CARE) pilot trial.

INTRODUCTION: The top research priority for cavernoma, identified by a James Lind Alliance Priority setting partnership was 'Does treatment (with neurosurgery or stereotactic radiosurgery) or no treatment improve outcome for people diagnosed with a cavernoma?' This pilot randomised controlled trial (RCT) aims to determine the feasibility of answering this question in a main phase RCT. METHODS AND ANALYSIS: We will perform a pilot phase, parallel group, pragmatic RCT involving approximately 60 children or adults with mental capacity, resident in the UK or Ireland, with an unresected symptomatic brain cavernoma. Participants will be randomised by web-based randomisation 1:1 to treatment with medical management and with surgery (neurosurgery or stereotactic radiosurgery) versus medical management alone, stratified by prerandomisation preference for type of surgery. In addition to 13 feasibility outcomes, the primary clinical outcome is symptomatic intracranial haemorrhage or new persistent/progressive focal neurological deficit measured at 6 monthly intervals. An integrated QuinteT Recruitment Intervention (QRI) evaluates screening logs, audio recordings of recruitment discussions, and interviews with recruiters and patients/parents/carers to identify and address barriers to participation. A Patient Advisory Group has codesigned the study and will oversee its progress. ETHICS AND DISSEMINATION: This study was approved by the Yorkshire and The Humber-Leeds East Research Ethics Committee (21/YH/0046). We will submit manuscripts to peer-reviewed journals, describing the findings of the QRI and the Cavernomas: A Randomised Evaluation (CARE) pilot trial. We will present at national specialty meetings. We will disseminate a plain English summary of the findings of the CARE pilot trial to participants and public audiences with input from, and acknowledgement of, the Patient Advisory Group. TRIAL REGISTRATION NUMBER: ISRCTN41647111.

Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma.

BACKGROUND: Traumatic acute subdural hematomas frequently warrant surgical evacuation by means of a craniotomy (bone flap replaced) or decompressive craniectomy (bone flap not replaced). Craniectomy may prevent intracranial hypertension, but whether it is associated with better outcomes is unclear. METHODS: We conducted a trial in which patients undergoing surgery for traumatic acute subdural hematoma were randomly assigned to undergo craniotomy or decompressive craniectomy. An inclusion criterion was a bone flap with an anteroposterior diameter of 11 cm or more. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOSE) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 12 months. Secondary outcomes included the GOSE rating at 6 months and quality of life as assessed by the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L). RESULTS: A total of 228 patients were assigned to the craniotomy group and 222 to the decompressive craniectomy group. The median diameter of the bone flap was 13 cm (interquartile range, 12 to 14) in both groups. The common odds ratio for the differences across GOSE ratings at 12 months was 0.85 (95% confidence interval, 0.60 to 1.18; P = 0.32). Results were similar at 6 months. At 12 months, death had occurred in 30.2% of the patients in the craniotomy group and in 32.2% of those in the craniectomy group; a vegetative state occurred in 2.3% and 2.8%, respectively, and a lower or upper good recovery occurred in 25.6% and 19.9%. EQ-5D-5L scores were similar in the two groups at 12 months. Additional cranial surgery within 2 weeks after randomization was performed in 14.6% of the craniotomy group and in 6.9% of the craniectomy group. Wound complications occurred in 3.9% of the craniotomy group and in 12.2% of the craniectomy group. CONCLUSIONS: Among patients with traumatic acute subdural hematoma who underwent craniotomy or decompressive craniectomy, disability and quality-of-life outcomes were similar with the two approaches. Additional surgery was performed in a higher proportion of the craniotomy group, but more wound complications occurred in the craniectomy group. (Funded by the National Institute for Health and Care Research; RESCUE-ASDH ISRCTN Registry number, ISRCTN87370545.).

Risk of Aneurysm Rupture (ROAR) study: protocol for a long-term, longitudinal, UK multicentre study of unruptured intracranial aneurysms.

INTRODUCTION: Unruptured intracranial aneurysms (UIA) are common in the adult population, but only a relatively small proportion will rupture. It is therefore essential to have accurate estimates of rupture risk to target treatment towards those who stand to benefit and avoid exposing patients to the risks of unnecessary treatment. The best available UIA natural history data are the PHASES study. However, this has never been validated and given the known heterogeneity in the populations, methods and biases of the constituent studies, there is a need to do so. There are also many potential predictors not considered in PHASES that require evaluation, and the estimated rupture risk is largely based on short-term follow-up (mostly 1 year). The aims of this study are to: (1) test the accuracy of PHASES in a UK population, (2) evaluate additional predictors of rupture and (3) assess long-term UIA rupture rates. METHODS AND ANALYSIS: The Risk of Aneurysm Rupture study is a longitudinal multicentre study that will identify patients with known UIA seen in neurosurgery units. Patients will have baseline demographics and aneurysm characteristics collected by their neurosurgery unit and then a single aggregated national cohort will be linked to databases of hospital admissions and deaths to identify all patients who may have subsequently suffered a subarachnoid haemorrhage. All matched admissions and deaths will be checked against medical records to confirm the diagnosis of aneurysmal subarachnoid haemorrhage. The target sample size is 20 000 patients. The primary outcome will be aneurysm rupture resulting in hospital admission or death. Cox regression models will be built to test each of the study's aims. ETHICS AND DISSEMINATION: Ethical approval has been given by South Central Hampshire A Research Ethics Committee (21SC0064) and Confidentiality Advisory Group support (21CAG0033) provided under Section 251 of the NHS Act 2006. The results will be disseminated in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ISRCTN17658526.

Vagus nerve stimulation paired with rehabilitation for stroke: Implantation experience from the VNS-REHAB trial.

OBJECTIVE: Vagus Nerve Stimulation (VNS) paired with rehabilitation delivered by the Vivistim® Paired VNS™ System was approved by the FDA in 2021 to improve motor deficits in chronic ischemic stroke survivors with moderate to severe arm and hand impairment. Vagus nerve stimulators have previously been implanted in over 125,000 patients for treatment-resistant epilepsy and the surgical procedure is generally well-tolerated and safe. In this report, we describe the Vivistim implantation procedure, perioperative management, and complications for chronic stroke survivors enrolled in the pivotal trial. METHODS: The pivotal, multisite, randomized, triple-blind, sham-controlled trial (VNS-REHAB) enrolled 108 participants. All participants were implanted with the VNS device in an outpatient procedure. Thrombolytic agents were temporarily discontinued during the perioperative period. Participants were discharged within 48 hrs and started rehabilitation therapy approximately 10 days after the Procedure. RESULTS: The rate of surgery-related adverse events was lower than previously reported for VNS implantation for epilepsy and depression. One participant had vocal cord paresis that eventually resolved. There were no serious adverse events related to device stimulation. Over 90% of participants were taking antiplatelet drugs (APD) or anticoagulants and no adverse events or serious adverse events were reported as a result of withholding these medications during the perioperative period. CONCLUSIONS: This study is the largest, randomized, controlled trial in which a VNS device was implanted in chronic stroke survivors. Results support the use of the Vivistim System in chronic stroke survivors, with a safety profile similar to VNS implantations for epilepsy and depression.

Antioxidant Therapeutic Strategies in Neurodegenerative Diseases.

The distinguishing pathogenic features of neurodegenerative diseases include mitochondrial dysfunction and derived reactive oxygen species generation. The neural tissue is highly sensitive to oxidative stress and this is a prominent factor in both chronic and acute neurodegeneration. Based on this, therapeutic strategies using antioxidant molecules towards redox equilibrium have been widely used for the treatment of several brain pathologies. Globally, polyphenols, carotenes and vitamins are among the most typical exogenous antioxidant agents that have been tested in neurodegeneration as adjunctive therapies. However, other types of antioxidants, including hormones, such as the widely used melatonin, are also considered neuroprotective agents and have been used in different neurodegenerative contexts. This review highlights the most relevant mitochondrial antioxidant targets in the main neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and Huntington's disease and also in the less represented amyotrophic lateral sclerosis, as well as traumatic brain injury, while summarizing the latest randomized placebo-controlled trials.

Advances in Visualizing Microglial Cells in Human Central Nervous System Tissue.

Neuroinflammation has recently been identified as a fundamentally important pathological process in most, if not all, CNS diseases. The main contributor to neuroinflammation is the microglia, which constitute the innate immune response system. Accurate identification of microglia and their reactivity state is therefore essential to further our understanding of CNS pathophysiology. Many staining techniques have been used to visualise microglia in rodent and human tissue, and immunostaining is currently the most frequently used. Historically, identification of microglia was predominantly based on morphological structure, however, recently there has been a reliance on selective antigen expression, and microglia-specific markers have been identified providing increased certainty that the cells observed are in fact microglia, rather than the similar yet distinct macrophages. To date, the most microglia-specific markers are P2Y12 and TMEM119. However, other microglia-related markers can also be useful for demonstrating activation state, phagocytic state, and for neuroimaging purposes in longitudinal studies. Overall, it is important to be aware of the microglia-selectivity issues of the various stains and immunomarkers used by researchers to distinguish microglia in CNS tissue to avoid misinterpretation.

Characterisation of Severe Traumatic Brain Injury Severity from Fresh Cerebral Biopsy of Living Patients: An Immunohistochemical Study.

Traumatic brain injury (TBI) is an extremely complex disease and current systems classifying TBI as mild, moderate, and severe often fail to capture this complexity. Neuroimaging cannot resolve the cellular and molecular changes due to lack of resolution, and post-mortem tissue examination may not adequately represent acute disease. Therefore, we examined the cellular and molecular sequelae of TBI in fresh brain samples and related these to clinical outcomes. Brain biopsies, obtained shortly after injury from 25 living adult patients suffering severe TBI, underwent immunohistochemical analysis. There were no adverse events. Immunostaining revealed various qualitative cellular and biomolecular changes relating to neuronal injury, dendritic injury, neurovascular injury, and neuroinflammation, which we classified into 4 subgroups for each injury type using the newly devised Yip, Hasan and Uff (YHU) grading system. Based on the Glasgow Outcome Scale-Extended, a total YHU grade of ≤8 or ≥11 had a favourable and unfavourable outcome, respectively. Biomolecular changes observed in fresh brain samples enabled classification of this heterogeneous patient population into various injury severity categories based on the cellular and molecular pathophysiology according to the YHU grading system, which correlated with outcome. This is the first study investigating the acute biomolecular response to TBI.

Applying Convolutional Neural Networks to Neuroimaging Classification Tasks: A Practical Guide in Python.

In this chapter, we describe the process of obtaining medical imaging data and its storage protocol. The authors also explain in a step-by-step approach how to extract and prepare the medical imaging data for machine learning algorithms. And finally, the process of building and assessing a convolutional neural network for medical imaging data is illustrated.

Fifth Generation Cellular Networks and Neurosurgery: A Narrative Review.

Connectivity is a driving force for productivity across a wide variety of sectors in the 21st century, with health care being no exception. Fifth generation cellular technology (5G) is frequently alluded to in the mainstream media but understanding of the technology and its potential impact is not widespread in clinical communities. It promises unprecedented improvement in speed, bandwidth, reliability, and latency, all of which have significant implications for the way we use wireless data. 5G can be subdivided into 3 parallel technological architectures: extended mobile broadband (eMBB), ultra-reliable low latency communication (URLLC), and massive machine type communication (mMTC). These domains each present different and exciting prospects for the future of health care. This narrative review aims to elucidate the nature of 5G, its context within the development of telecommunications, and describe some of the notable opportunities it presents to the neurosurgical community. In many cases the requisite hardware has already been developed, but use has been limited by the requirements of a fast, reliable, and omnipresent network connection. Examples include telesurgical robots, remote supervision of procedures, integrated smart operating rooms, and clinician telepresence. The events of 2020 and the COVID-19 pandemic have brought the world's attention to digital transformation. The mechanics of 5G connectivity creates the capacity for these changes to be applied practically. An understanding of this technology is essential to appreciate the development and opportunities which will be part of our professional future.

Clinical Application of Shear Wave Elastography for Assisting Brain Tumor Resection.

BACKGROUND: The clinical outcomes for brain tumor resection have been shown to be significantly improved with increased extent of resection. To achieve this, neurosurgeons employ different intra-operative tools to improve the extent of resection of brain tumors, including ultrasound, CT, and MRI. Young's modulus (YM) of brain tumors have been shown to be different from normal brain but the accuracy of SWE in assisting brain tumor resection has not been reported. AIMS: To determine the accuracy of SWE in detecting brain tumor residual using post-operative MRI scan as "gold standard". METHODS: Thirty-four patients (aged 1-62 years, M:F = 15:20) with brain tumors were recruited into the study. The intraoperative SWE scans were performed using Aixplorer® (SuperSonic Imagine, France) using a sector transducer (SE12-3) and a linear transducer (SL15-4) with a bandwidth of 3 to 12 MHz and 4 to 15 MHz, respectively, using the SWE mode. The scans were performed prior, during and after brain tumor resection. The presence of residual tumor was determined by the surgeon, ultrasound (US) B-mode and SWE. This was compared with the presence of residual tumor on post-operative MRI scan. RESULTS: The YM of the brain tumors correlated significantly with surgeons' findings (ρ = 0.845, p < 0.001). The sensitivities of residual tumor detection by the surgeon, US B-mode and SWE were 36%, 73%, and 94%, respectively, while their specificities were 100%, 63%, and 77%, respectively. There was no significant difference between detection of residual tumor by SWE, US B-mode, and MRI. SWE and MRI were significantly better than the surgeon's detection of residual tumor (p = 0.001 and p < 0.001, respectively). CONCLUSIONS: SWE had a higher sensitivity in detecting residual tumor than the surgeons (94% vs. 36%). However, the surgeons had a higher specificity than SWE (100% vs. 77%). Therefore, using SWE in combination with surgeon's opinion may optimize the detection of residual tumor, and hence improve the extent of brain tumor resection.

The Exoscope versus operating microscope in microvascular surgery: A simulation non-inferiority trial.

BACKGROUND: The Exoscope is a novel high-definition digital camera system. There is limited evidence signifying the use of exoscopic devices in microsurgery. This trial objectively assesses the effects of the use of the Exoscope as an alternative to the standard operating microscope (OM) on the performance of experts in a simulated microvascular anastomosis. METHODS: Modus V Exoscope and OM were used by expert microsurgeons to perform standardized tasks. Hand-motion analyzer measured the total pathlength (TP), total movements (TM), total time (TT), and quality of end-product anastomosis. A clinical margin of TT was performed to prove non-inferiority. An expert performed consecutive microvascular anastomoses to provide the exoscopic learning curve until reached plateau in TT. RESULTS: Ten micro sutures and 10 anastomoses were performed. Analysis demonstrated statistically significant differences in performing micro sutures for TP, TM, and TT. There was statistical significance in TM and TT, however, marginal non-significant difference in TP regarding microvascular anastomoses performance. The intimal suture line analysis demonstrated no statistically significant differences. Non-inferiority results based on clinical inferiority margin (Δ) of TT=10 minutes demonstrated an absolute difference of 0.07 minutes between OM and Exoscope cohorts. A 51%, 58%, and 46% improvement or reduction was achieved in TT, TM, TP, respectively, during the exoscopic microvascular anastomosis learning curve. CONCLUSIONS: This study demonstrated that experts' Exoscope anastomoses appear non-inferior to the OM anastomoses. Exoscopic microvascular anastomosis was more time consuming but end-product (patency) in not clinically inferior. Experts' "warm-up" learning curve is steep but swift and may prove to reach clinical equality.

The Silk Vista Baby: Initial experience and report of two cases.

In this report, we present two cases using a novel flow diverter, the Silk Vista Baby, to treat aneurysms successfully, both ruptured and unruptured, that would have been difficult to treat using alternative flow diverters. We describe the clinical and radiological features, outcome and the unique features of the Silk Vista Baby flow diverter.

Further characterization of changes in axial strain elastograms due to the presence of slippery tumor boundaries.

Elastography measures tissue strain, which can be interpreted under certain simplifying assumptions to be representative of the underlying stiffness distribution. This is useful in cancer diagnosis where tumors tend to have a different stiffness to healthy tissue and has also shown potential to provide indication of the degree of bonding at tumor-tissue boundaries, which is clinically useful because of its dependence on tumor pathology. We consider the changes in axial strain for the case of a symmetrical model undergoing uniaxial compression, studied by characterizing changes in tumor contrast transfer efficiency (CTE), inclusion to background strain contrast and strain contrast generated by slip motion, as a function of Young's modulus contrast and applied strain. We present results from a finite element simulation and an evaluation of these results using tissue-mimicking phantoms. The simulation results show that a discontinuity in displacement data at the tumor boundary, caused by the surrounding tissue slipping past the tumor, creates a halo of "pseudostrain" across the tumor boundary. Mobile tumors also appear stiffer on elastograms than adhered tumors, to the extent that tumors that have the same Young's modulus as the background may in fact be visible as low-strain regions, or those that are softer than the background may appear to be stiffer than the background. Tumor mobility also causes characteristic strain heterogeneity within the tumor, which exhibits low strain close to the slippery boundary and increasing strain toward the center of the tumor. These results were reproduced in phantom experiments. In addition, phantom experiments demonstrated that when fluid lubrication is present at the boundary, these effects become applied strain-dependent as well as modulus-dependent, in a systematic and characteristic manner. The knowledge generated by this study is expected to aid interpretation of clinical strain elastograms by helping to avoid misinterpretation as well as provide additional diagnostic criteria stated in the paper and stimulate further research into the application of elastography to tumor mobility assessment.

Vessel wall MRI and intracranial aneurysms.

: Vessel wall magnetic resonance imaging (MRI) is a novel imaging technique that allows the intracranial vessel walls to be imaged directly. This state-of the art imaging modality may potentially change the way aneurysms are evaluated and managed. In this short review we discuss the current knowledge with illustrative cases.

A novel technique of detecting MRI-negative lesion in focal symptomatic epilepsy: intraoperative ShearWave elastography.

Focal symptomatic epilepsy is the most common form of epilepsy that can often be cured with surgery. A small proportion of patients with focal symptomatic epilepsy do not have identifiable lesions on magnetic resonance imaging (MRI). The most common pathology in this group is type II focal cortical dysplasia (FCD), which is a subtype of malformative brain lesion associated with medication-resistant epilepsy. We present a patient with MRI-negative focal symptomatic epilepsy who underwent invasive electrode recordings. At the time of surgery, a novel ultrasound-based technique called ShearWave Elastography (SWE) was performed. A 0.5 cc lesion was demonstrated on SWE but was absent on B-mode ultrasound and 3-T MRI. Electroencephalography (EEG), positron emission tomography (PET), and magnetoencephalography (MEG) scans demonstrated an abnormality in the right frontal region. On the basis of this finding, a depth electrode was implanted into the lesion. Surgical resection and histology confirmed the lesion to be type IIb FCD. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

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

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

A new method for the acquisition of ultrasonic strain image volumes.

This article presents a new method for acquiring three-dimensional (3-D) volumes of ultrasonic axial strain data. The method uses a mechanically-swept probe to sweep out a single volume while applying a continuously varying axial compression. Acquisition of a volume takes 15-20 s. A strain volume is then calculated by comparing frame pairs throughout the sequence. The method uses strain quality estimates to automatically pick out high quality frame pairs, and so does not require careful control of the axial compression. In a series of in vitro and in vivo experiments, we quantify the image quality of the new method and also assess its ease of use. Results are compared with those for the current best alternative, which calculates strain between two complete volumes. The volume pair approach can produce high quality data, but skillful scanning is required to acquire two volumes with appropriate relative strain. In the new method, the automatic quality-weighted selection of image pairs overcomes this difficulty and the method produces superior quality images with a relatively relaxed scanning technique.