Anaesthesia for mechanical thrombectomy: a narrative review.

Stroke is a leading cause of death and disability, and is associated with a huge societal and economic burden. Interventions for the immediate treatment of ischaemic stroke due to large vessel occlusion are dependent on recanalisation of the occluded vessel. Trials have provided evidence supporting the efficacy of mechanical thrombectomy in ischaemic stroke due to large vessel occlusion. This has resulted in changes in management and organisation of stroke care worldwide. Major determinants of effectiveness of thrombectomy include: time between stroke onset and reperfusion; location of occlusion and local collateral perfusion; adequacy of reperfusion; patient age; and stroke severity. The role of anaesthetic technique on outcome remains controversial with published research showing conflicting results. As a result, choice of conscious sedation or general anaesthesia for mechanical thrombectomy is often dependent on individual operator choice or institutional preference. More recent randomised controlled trials have suggested that protocol-driven general anaesthesia is no worse than conscious sedation and may even be associated with better outcomes. These and other studies have highlighted the importance of optimal blood pressure management as a major determinant of patient outcome. Anaesthetic management should be tailored to the individual patient and circumstances. Acute ischaemic stroke is a neurological emergency; clinicians should focus on minimising door-to-groin puncture time and the provision of high-quality periprocedural care with a particular emphasis on the maintenance of an adequate blood pressure.

Guidelines for safe transfer of the brain-injured patient: trauma and stroke, 2019: Guidelines from the Association of Anaesthetists and the Neuro Anaesthesia and Critical Care Society.

The location of care for many brain-injured patients has changed since 2012 following the development of major trauma centres. Advances in management of ischaemic stroke have led to the urgent transfer of many more patients. The basis of care has remained largely unchanged, however, with emphasis on maintaining adequate cerebral perfusion as the key to preventing secondary injury. Organisational aspects and training for transfers are highlighted, and we have included an expanded section on paediatric transfers. We have also provided a table with suggested blood pressure parameters for the common types of brain injury but acknowledge that there is little evidence for many of our recommendations. These guidelines remain a mix of evidence-based and consensus-based statements. We have received assistance from many organisations representing clinicians who care for these patients, and we believe our views represent the best of current thinking and opinion. We encourage departments to review their own practice using our suggestions for audit and quality improvement.

Access to assistive technology for people with intellectual disabilities: a systematic review to identify barriers and facilitators.

BACKGROUND: The World Health Organisation has launched a programme to promote Global Cooperation on Assistive Technology. Its aim is to increase access to high-quality affordable assistive products (AP) for everybody in need. People with intellectual disabilities (ID) are a specific group that could benefit from AP, but use less AP compared to their non-intellectual disabled peers. METHOD: A systematic literature search was carried out to identify barriers and potential facilitators for access to AP for people with ID globally. The search strategy terms were 'Intellectual Disability' and 'Assistive Technology' with the following electronic literature databases PubMed, Embase, ASSIA, Web of Science, Medline, CINAHL complete, PsycInfo, Scopus and ERIC. The quality and relevance of the studies were assessed. Factors associated with access were identified thematically, categorised into barriers and facilitators and mapped into themes. RESULTS: In all, 22 key studies were retrieved, describing 77 barriers and 56 facilitators. The most frequently reported barriers were related to lack of funding and cost of AP, lack of awareness about AP and inadequate assessment. An increase of knowledge and awareness about AP and the need of AP for people with ID were most often extracted as factors that could potentially facilitate access. CONCLUSIONS: This review proposes actions linked to the barriers and facilitators that have a particular importance for people with ID to access AP. Yet, only limited research is available describing factors that influence access to AP for people with ID in low and middle income countries and rural areas.

Transplanted xenogeneic neural cells in neurodegenerative disease models exhibit remarkable axonal target specificity and distinct growth patterns of glial and axonal fibres.

Clinical trials are under way using fetal cells to repair damaged neuronal circuitry. However, little is known about how transplanted immature neurons can grow anatomically correct connections in the adult central nervous system (CNS). We transplanted embryonic porcine neural cells in vivo into adult rat brains with neuronal and axonal loss typical of Parkinson's or Huntington's disease. Using complementary species-specific cellular markers, we found donor axons and CD44+ astroglial fibres in host white matter tracts up to 8 mm from CNS transplant sites, although only donor axons were capable of reaching correct gray matter target regions. This work demonstrates that adult host brain can orient growth of transplanted neurons and that there are differences in transplant donor glial and axonal growth patterns in cellular repair of the mature CNS.

Histological evidence of fetal pig neural cell survival after transplantation into a patient with Parkinson's disease.

The movement disorder in Parkinson's disease results from the selective degeneration of a small group of dopaminergic neurons in the substantia nigra pars compacta region of the brain. A number of exploratory studies using human fetal tissue allografts have suggested that transplantation of dopaminergic neurons may become an effective treatment for patients with Parkinson's disease and the difficulty in obtaining human fetal tissue has generated interest in finding corresponding non-human donor cells. Here we report a post-mortem histological analysis of fetal pig neural cells that were placed unilaterally into the caudate-putamen brain region of a patient suffering from Parkinson's disease. Long-term (over seven months) graft survival was found and the presence of pig dopaminergic neurons and other pig neural and glial cells is documented. Pig neurons extended axons from the graft sites into the host brain. Furthermore, other graft derived cells were observed several millimeters from the implantation sites. Markers for human microglia and T-cells showed only low reactivity in direct proximity to the grafts. This is the first documentation of neural xenograft survival in the human brain and of appropriate growth of non-human dopaminergic neurons for a potential therapeutic response in Parkinson's disease.

Hyperglycaemia and cerebral oedema in a patient with a meningioma receiving dexamethasone.

Dexamethasone is prescribed routinely to reduce cerebral oedema in neurosurgical patients undergoing craniotomy for tumour and is used increasingly as an anti-emetic. Dexamethasone, however, has been shown to cause hyperglycaemia. We describe a case of hyperglycaemic crisis, cerebral oedema and death secondary to dexamethasone in a patient with a frontal meningioma. We highlight the risks of peri-operative dexamethasone and discuss the diagnosis, treatment and complications of hyperglycaemic crises and cerebral oedema.

Comparison of droplet spread in standard and laminar flow operating theatres: SPRAY study group.

BACKGROUND: Reducing COVID-19 transmission relies on controlling droplet and aerosol spread. Fluorescein staining reveals microscopic droplets. AIM: To compare the droplet spread in non-laminar and laminar air flow operating theatres. METHODS: A 'cough-generator' was fixed to a theatre trolley at 45°. Fluorescein-stained 'secretions' were projected on to a series of calibrated targets. These were photographed under UV light and 'source detection' software measured droplet splatter size and distance. FINDINGS: The smallest droplet detected was ∼120 µm and the largest ∼24,000 µm. An average of 25,862 spots was detected in the non-laminar theatre, compared with 11,430 in the laminar theatre (56% reduction). The laminar air flow mainly affected the smaller droplets (<1000 µm). The surface area covered with droplets was: 6% at 50 cm, 1% at 2 m, and 0.5% at 3 m in the non-laminar air flow; and 3%, 0.5%, and 0.2% in the laminar air flow, respectively. CONCLUSION: Accurate mapping of droplet spread in clinical environments is possible using fluorescein staining and image analysis. The laminar air flow affected the smaller droplets but had limited effect on larger droplets in our 'aerosol-generating procedure' cough model. Our results indicate that the laminar air flow theatre requires similar post-surgery cleaning to the non-laminar, and staff should consider full personal protective equipment for medium- and high-risk patients.

Transplantation of embryonic porcine mesencephalic tissue in patients with PD.

OBJECTIVE: To assess the safety and the effect on standardized clinical rating measures of transplanted embryonic porcine ventral mesencephalic (VM) tissue in advanced PD. METHODS: Twelve patients with idiopathic PD underwent unilateral implantation of embryonic porcine VM tissue; six received cyclosporine immunosuppression and six received tissue treated with a monoclonal antibody directed against major histocompatibility complex class I. Patients were followed for 12 months and assessed by clinical examination, MRI, and 18F-levodopa PET. Porcine endogenous retrovirus testing was conducted by PCR-based method on peripheral blood mononuclear cells. RESULTS: Cell implantation occurred without serious adverse events in all patients. Cultures were negative for bacterial and unknown viral contamination. No porcine endogenous retrovirus DNA sequences were found. MRI demonstrated cannula tracts within the putamen and caudate, with minimal or no edema and no mass effect at the transplant sites. In the medication-off state, total Unified Parkinson's Disease Rating Scale scores improved 19% (p = 0.01). Three patients improved over 30%. There were two patients with improved gait. 18F-levodopa PET failed to show changes on the transplanted side. CONCLUSIONS: Unilateral transplantation of porcine embryonic VM cells into PD patients was well tolerated with no evidence of transmission of porcine endogenous retrovirus. Changes in standardized clinical PD rating measures were variable, similar to the results of the first trials of unilateral human embryonic allografts that transplanted small amounts of tissue.

No evidence for infection of human cells with porcine endogenous retrovirus (PERV) after exposure to porcine fetal neuronal cells.

BACKGROUND: Recent demonstration of human cell infection in vitro with porcine endogenous retrovirus (PERV) has raised safety concerns for new therapies that involve transplantation of pig cells or organs to humans. To assess better the specific risk that may be associated with the transplantation of fetal pig neuronal cells to the central nervous system of patients suffering from intractable neurologic disorders (Parkinson's disease, Huntington's disease, and epilepsy), we have performed studies to determine whether there is evidence for in vivo or in vitro transmission of PERV from fetal pig neuronal cells to human cells. METHODS: Ventral mesencephalon (VM) and lateral ganglionic eminence cells were isolated from fetal pigs and transplanted into patients with neurological conditions as part of clinical studies. Blood samples taken from patients at various time points posttransplant were tested for evidence of PERV. In vitro studies to test for PERV infection of human cells after cocultivation with either fetal porcine ventral mesencephalon or porcine fetal lateral ganglionic eminence cells were also performed. RESULTS: We found no evidence of PERV provirus integration in the DNA from PBMC of 24 neuronal transplant recipients. In addition, no PERV was released from cultured fetal porcine neuronal cultures, and there was no transfer of PERV from fetal pig neuronal cells to human cells in vitro. CONCLUSIONS: Our results demonstrate by both examination of transplant patient blood samples and in vitro studies that there is no evidence for transmission of PERV from porcine fetal neural cells to human cells.

A novel mode of immunoprotection of neural xenotransplants: masking of donor major histocompatibility complex class I enhances transplant survival in the central nervous system.

To determine the role of major histocompatibility complex (MHC) class I in immunological rejection of neural xenotransplants, F(ab')2 fragments of a monoclonal antibody to porcine MHC class I were used to mask this complex on porcine fetal striatal cells transplanted into rat striata previously lesioned with quinolinic acid. Presence of MHC class I on the surface of porcine striatal cells was confirmed by fluorescence-activated cell sorting prior to F(ab')2 treatment. At three to four months post-transplantation, survival of F(ab')2-treated xenografts was assessed by means of donor-specific immunostaining and compared to that of untreated xenografts in non-immunosuppressed rats and in rats immunosuppressed with cyclosporine A. In this study, masking of donor MHC class I by F(ab')2 treatment resulted in enhanced xenografts survival compared to the non-immunosuppressed controls (graft survival rates, 52% and 7%, respectively; P < 0.005) at survival times up to four months. While xenograft survival in F(ab')2-treated animals was not significantly different from that in cyclosporine-treated rats (74% graft survival), mean graft volume in F(ab')2-treated animals was smaller than that in cyclosporine-treated animals (1.07 +/- 0.30 mm3 versus 3.14 +/- 0.51 mm3; P < 0.005). The cytoarchitectonic organization of the xenografts was similar in F(ab')2- and cyclosporine-treated animals, and grafts in both groups exhibited long distance target-directed axonal outgrowth. The pattern of immunoreactivity to porcine MHC class I in the xenografts corresponded to the regional distribution of donor glia. In xenografts undergoing rejection, infiltration with host inflammatory cells was restricted to necrotic graft remnants and spared the nearby host structures. We conclude that MHC class-I-restricted immune mechanisms play an important role in neural xenograft rejection and that masking of this complex on donor cells may provide a useful strategy for immunoprotection of neural xenografts.

Xenogeneic cell therapy: current progress and future developments in porcine cell transplantation.

The multitude of distinct cell types present in mature and developing tissues display unique physiologic characteristics. Cellular therapy is a novel technology with the promise of utilizing this diversity to treat a wide range of human degenerative diseases. Intractable diseases, disorders, and injuries are characterized by cell death or aberrant cellular function. Cell transplantation can replace diseased or lost tissue to provide restorative therapy for these conditions. The limited use of cell transplants as a basis for current therapy can, in part, be attributed to the lack of available human cells suitable for transplantation. This has prevented further realization of the promise of cell transplantation as a platform technology. Accordingly, cell-based therapies such as blood transfusions, for which the cells are readily available, are a standard part of current medical practice. Despite numerous attempts to expand primary human cells in tissue culture, current technological limitations of this approach in regard to proliferative capacity and maintenance of the differentiated phenotype has prevented their use for transplantation. Further, use of human stem cells for the derivation of specific cell types for transplantation is an area of future application with great potential, but hurdles remain in regard to deriving and sufficiently expanding these multipotential cells. Thus, it appears that primary cells are at present a superior source for transplantation. This review focuses on pigs as a source of a variety of primary cells to advance cell therapy to the clinic and implement achievement of its full potential. We outline the advantages and disadvantages of xenogeneic cell therapy while underscoring the utility of transplantable porcine cells for the treatment of human disease.

Extensive axonal and glial fiber growth from fetal porcine cortical xenografts in the adult rat cortex.

Axonal growth from cortically placed fetal neural transplants to subcortical targets in adult hosts has been difficult to demonstrate and is assumed to be minimal; however, experiments using xenogeneic neural grafts of either human or porcine fetal tissues into the adult rat striatum, mesencephalon, and spinal cord have demonstrated the capability for long-distance axonal growth. This study reports similar results for porcine cortical xenografts placed in the adult rat cerebral cortex and compares these findings with results from cortical allografts. Adult rats that previously received unilateral cortical lesions by an oblique intracortical stereotaxic injection of quinolinic acid, were implanted with suspensions of either E14 rat or E38 xenogeneic porcine fetal cortical cells. Xenografted rats were immunosuppressed by cyclosporin A. The corpus callosum was intact in all cases and grafts were confined to the overlying cortex. After a 31-34 wk posttransplant survival period, acetylcholinesterase (AChE) staining and tyrosine hydroxylase (TH) immunocytochemistry revealed that both allo- and xenografts received host afferents. Retrograde tracer injections into the ipsilateral striatum and cerebral peduncle in allografted animals failed to show any axonal growth to either subcortical target. Using a porcine-specific axonal marker in xenografted animals, we found graft axons in white matter tracts (corpus callosum, internal capsule, cingulum bundle, and medial forebrain bundle) and within the caudate-putamen and both the ipsilateral and contralateral cerebral cortex. Graft axons were not found in the thalamus, midbrain, or spinal cord. In addition, using an antibody to porcine glial fibers, we observed more extensive graft glial fiber growth into the same host fiber tracts, as far caudally as the cerebral peduncle, but not into gray matter targets outside the cortex. These results demonstrate that porcine cortical xenograft axons and glia can extend from lesioned cerebral cortex to cortical and subcortical targets in the adult rat brain. These findings are relevant for prospects of repairing cortical damage and obtaining functional recovery.