Surgery for Malignant Acute Ischemic Stroke: A Narrative Review of the Knowns and Unknowns.

Malignant acute ischemic stroke (AIS) is characterized by acute neurological deterioration caused by progressive space-occupying brain edema, often occurring in the first hours to days after symptom onset. Without any treatment, the result is often fatal. Despite advances in treatment for AIS, up to 80% of patients with a large hemispheric stroke or cerebellar stroke are at risk of poor outcome. Decompressive surgery can be life-saving in a subgroup of patients with malignant AIS, but uncertainties exist on patient selection, predictors of malignant infarction, perioperative management, and timing of intervention. Although survivors are left disabled, most agree with the original decision to undergo surgery and would make the same decision again. In this narrative review, we focus on the clinical and radiological predictors of malignant infarction in AIS and outline the technical aspects of decompressive surgery as well as duraplasty and cranioplasty. We discuss the current evidence and recommendations for surgery in AIS, highlighting gaps in knowledge, and suggest directions for future studies. KEY POINTS: · Acute ischemic stroke from occlusion of a proximal intracranial artery can progress quickly to malignant edema, which can be fatal in 80% of patients despite medical management.. · Decompression surgery is life-saving within 48 hours of stroke onset, but the benefits beyond this time and in the elderly are unknown.. · Decompressive surgery is associated with high morbidity, particularly in the elderly. The decision to operate must be made after considering the individual's preference and expectations of quality of life in the context of the clinical condition.. · Further studies are needed to refine surgical technique including value of duraplasty and understand the role monitoring intracranial pressure during and after decompressive surgery.. · More studies are needed on the pathophysiology of malignant cerebral edema, prediction models including imaging and biomarkers to identify which subgroup of patients will benefit from decompressive surgery.. · More research is needed on factors associated with morbidity and mortality after cranioplasty, safety and efficacy of implants, and comparisons between them.. · Further studies are needed to assess the long-term effects of physical disability and quality of life of survivors after surgery, particularly those with severe neurological deficits..

Interventions for preventing and ameliorating cognitive deficits in adults treated with cranial irradiation.

BACKGROUND: Cognitive deficits are common in people who have received cranial irradiation and have a serious impact on daily functioning and quality of life. The benefit of pharmacological and non-pharmacological treatment of cognitive deficits in this population is unclear. This is an updated version of the original Cochrane Review published in Issue 12, 2014. OBJECTIVES: To assess the effectiveness of interventions for preventing or ameliorating cognitive deficits in adults treated with cranial irradiation. SEARCH METHODS: For this review update we searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Embase via Ovid, and PsycInfo via Ovid to 12 September 2022. SELECTION CRITERIA: We included randomised controlled (RCTs) trials that evaluated pharmacological or non-pharmacological interventions in cranial irradiated adults, with objective cognitive functioning as a primary or secondary outcome measure. DATA COLLECTION AND ANALYSIS: Two review authors (MK, JD) independently extracted data from selected studies and carried out a risk of bias assessment. Cognitive function, fatigue and mood outcomes were reported. No data were pooled. MAIN RESULTS: Eight studies met the inclusion criteria and were included in this updated review. Six were from the original version of the review, and two more were added when the search was updated. Nineteen further studies were assessed as part of this update but did not fulfil the inclusion criteria. Of the eight included studies, four studies investigated "prevention" of cognitive problems (during radiotherapy and follow-up) and four studies investigated "amelioration" (interventions to treat cognitive impairment as a late complication of radiotherapy). There were five pharmacological studies (two studies on prevention and three in amelioration) and three non-pharmacological studies (two on prevention and one in amelioration). Due to differences between studies in the interventions being evaluated, a meta-analysis was not possible.  Studies in early radiotherapy treatment phase (five studies) Pharmacological studies in the "early radiotherapy treatment phase" were designed to prevent or ameliorate cognitive deficits and included drugs used in dementia (memantine) and fatigue (d-threo-methylphenidate hydrochloride). Non-pharmacological studies in the "early radiotherapy treatment phase" included a ketogenic diet and a two-week cognitive rehabilitation and problem-solving programme.  In the memantine study, the primary cognitive outcome of memory at six months did not reach significance, but there was significant improvement in overall cognitive function compared to placebo, with similar adverse events across groups. The d-threo-methylphenidate hydrochloride study found no statistically significant difference between arms, with few adverse events. The study of a calorie-restricted ketogenic diet found no effect, although a lower than expected calorie intake in the control group complicates interpretation of the results.  The study investigating the utility of a rehabilitation program did not carry out a statistical comparison of cognitive performance between groups.  Studies in delayed radiation or late effect phase (four studies) The "amelioration" pharmacological studies to treat cognitive complications of radiotherapy included drugs used in dementia (donepezil) or psychostimulants (methylphenidate and modafinil). Non-pharmacological measures included cognitive rehabilitation and problem solving (Goal Management Training). These studies included patients with cognitive problems at entry who had "stable" brain cancer.  The donepezil study did not find an improvement in the primary cognitive outcome of overall cognitive performance, but did find improvement in an individual test of memory, compared to placebo; adverse events were not reported. A study comparing methylphenidate with modafinil found improvements in cognitive function in both the methylphenidate and modafinil arms; few adverse events were reported. Another  study comparing two different doses of modafinil combined treatment arms and found improvements across all cognitive tests, however, a number of adverse events were reported. Both studies were limited by a small sample size. The Goal Management Training study suggested a benefit of the intervention, a behavioural intervention that combined mindfulness and strategy training, on executive function and processing speed.  There were a number of limitations across studies and few were without high risks of bias. AUTHORS' CONCLUSIONS: In this update, limited additional evidence was found for the treatment or amelioration of cognitive deficits in adults treated with cranial irradiation. As concluded in the original review, there is supportive evidence that memantine may help prevent cognitive deficits for adults with brain metastases receiving cranial irradiation. There is supportive evidence that donepezil, methylphenidate and modafinil may have a role in treating cognitive deficits in adults with brain tumours who have been treated with cranial irradiation; patient withdrawal affected the statistical power of these studies. Further research that tries to minimise the withdrawal of consent, and subsequently reduce the requirement for imputation procedures, may offer a higher certainty of evidence. There is evidence from only a single small study to support non-pharmacological interventions in the amelioration of cognitive deficits. Further research is required.

Psychrobacter piechaudii shunt infection: first report of human infection.

Psychrobacter piechaudii is a recently described species of Gram-negative bacteria in the Moraxellaceae family. No cases of human infection due to this species have been described before. We report the case of an ex-premature infant girl with hydrocephalus secondary to intraventricular haemorrhage who underwent multiple cerebrospinal fluid (CSF) shunt operations. She ultimately developed Psychrobacter piechaudii meningitis, presenting as ventriculoperitoneal shunt dysfunction and wound leak, which necessitated removal of the shunt, a period of external ventricular drainage and antibiotics. We found this organism to be sensitive to intravenous ceftazidime (50 mg/kg) and ciprofloxacin, and a 7-10 day treatment course prior to shunt re-insertion (and 3 week total course) was sufficient. The patient is well post-operatively. To the best of our knowledge, this is the first reported case of Psychrobacter piechaudii infection in a human.

Beating a skullduggerous infantile hemispheric high-grade glioma.

A case of infantile hemispheric high grade glioma in a five-month-old boy is presented. Striking images of a 'beaten copper pot' skull were concerning at first, but with a successful surgical and oncological plan he is well three years later, displaying only minor signs of developmental delay.

Experience with awake throughout craniotomy in tumour surgery: technique and outcomes of a prospective, consecutive case series with patient perception data.

BACKGROUND: Awake craniotomy is the standard of care in surgery of tumours located in eloquent parts of the brain. However, high variability is recorded in multiple parameters, including anaesthetic techniques, mapping paradigms and technology adjuncts. The current study is focused primarily on patients' level of consciousness, surgical technique, and experience based on a cohort of 50 consecutive cases undergoing awake throughout craniotomy (ATC). METHODS: Data was collected prospectively for 46 patients undergoing 50 operations over 14-month period, by the senior author, including demographics, extent of resection (EOR), adverse intraoperative events, surgical morbidity, surgery duration, levels of O2 saturation and brain oedema. A prospective, patient experience questionnaire was delivered to 38 patients. RESULTS: The ATC technique was well tolerated in all patients. Once TCI stopped, all patients were immediately assessable for mapping. Despite > 75% of cases being considered inoperable/high risk, gross total resection (GTR) was achieved in 68% patients and subtotal resection in 20%. The average duration of surgery was 220 min with no episodes of hypoxia. Early and late severe deficits recorded in 12% and 2%, respectively. No stimulation-induced seizures or failed ATCs were recorded. Patient-recorded data showed absent/minimal pain during (1) clamp placement in 95.6% of patients; (2) drilling in 94.7% of patients; (3) surgery in 78.9% of patients. Post-operatively, 92.3% of patients reported willingness to repeat the ATC, if necessary. CONCLUSIONS: The current ATC paradigm allows immediate brain mapping, maximising patient comfort during self-positioning. Despite the cohort of challenging tumour location, satisfactory EOR was achieved with acceptable morbidity and no adverse intraoperative events.

Childhood medulloblastoma-a single institution's historical perspective on survival and functional morbidity.

PURPOSE: To compare results from a third (1995-2010) cohort of children with medulloblastoma with two previous series (J Neurosurg 86:13-21, 1997; Arch Dis Child 54:200-203, 1979) to analyse the effects of management changes aimed at improving both overall and event-free survivals (OS and EFS) and functional outcomes. METHODS: Review of neuro-oncology and imaging databases and previously published results. RESULTS: There was no statistically significant improvement in the 5-year OS for 104 children diagnosed 1995-2010, 61.5% (95% CI, 52.9, 71.6), compared with 50% of the 80 children presenting 1980-1990 (J Neurosurg 86:13-21, 1997) (difference 11.5%; 95% CI, 2.8, 25.4). Five-year OS for 96 children suitable for risk-stratification was overall 66% (95% CI, 57.9, 75.8); standard risk 77.8% (95% CI, 67.4, 89.7); high risk < 3 years 50.0% (95% CI, 32.3, 77.5); high risk ≥ 3 years 54.5% (95% CI, 37.2, 79.9); 5-year EFS were standard risk 68.5% (95% CI, 57.2, 82.1); high risk < 3 years 40.0% (95% CI, 23.4, 68.4); and high risk ≥ 3 years 36.4% (95% CI, 20.9, 63.2); overall 55.2% (95% CI, 46.1, 66.1). Of 62/63 ≥ 5-year survivor, 9 died later from tumour relapse and 4 from second malignancy. Functional outcomes of 62 of the 63 ≥ 5-year survivors: 67.7% had educational issues requiring remedial input; 18% restricted mobility indoors and outdoors; 59.7% hearing impairment (42% prescribed aids). CONCLUSIONS: 1. Comparison of this single-institution series with its predecessor found that revised chemotherapy and RT protocols and greater accuracy of risk stratification did not result in statistically significant improvements in either survival or treatment-related functional disability. 2. Extended (> 5-year) follow-up is essential if 20% of late deaths from relapse and second malignancies are not to be overlooked.

Endoscopic surgery for intraventricular arachnoid cysts in children: clinical presentation, radiological features, management, and outcomes over a 12-year period.

PURPOSE: Less than 0.5% of arachnoid cysts are intraventricular in origin. We review our experience with endoscopic surgery for intraventricular arachnoid cysts in children. METHODS: This is a retrospective review of children with intraventricular arachnoid cysts who underwent surgery between 2005 and 2016. Clinical notes and imaging were reviewed. RESULTS: Twenty-nine patients with endoscopically treated intraventricular arachnoid cysts were identified (M/F = 17:12; median age = 1.47 years, range = 7 days-13 years). All had hydrocephalus at presentation, many had symptoms/signs of raised intracranial pressure, and five (17%) were asymptomatic. Cysts were treated with fenestration into the ventricle alone (ventriculocystostomy [VC], n = 14), fenestration into the ventricle and cisternostomy (ventriculocystostomy plus cisternostomy [VC + C], n = 14), or endoscopic third ventriculostomy alone (n = 1). Six (21%) patients experienced transient and/or conservatively managed complications. Further surgery was required in 12 (41%). Revision-free survival was significantly shorter with VC compared to VC + C (log rank p = 0.049), and the majority of VC/VC + C revisions (n = 8 of 11, 73%) were required within 6 months of initial endoscopic surgery. One (3%) patient died during follow-up, from unrelated pathology. After a median follow-up of 67.5 months in survivors (range = 5.5-133.5 months), 24 (83%) cases were clinically and radiologically stable without a shunt in situ. CONCLUSIONS: Endoscopic fenestration is safe and effective in most intraventricular arachnoid cysts. Additional cisternostomy at the time of cyst fenestration into the ventricle significantly improved revision-free survival in our cohort. Endoscopic surgery should be the first-line therapy when considering intervention for symptomatic intraventricular arachnoid cysts and for asymptomatic cysts increasing in size on serial imaging.

Outcomes in children with central nervous system tumors disseminated at presentation: a large single-center experience.

PURPOSE: Children with disseminated central nervous system (CNS) tumors have worse outcomes than those with solitary disease, but outcomes of disease dissemination at initial presentation have not been systematically studied and compared across tumor groups to date. We evaluated the impact of tumor dissemination at presentation on management and clinical outcomes in a cohort of consecutively treated children in a single neurosurgical unit over a 14-year period. METHODS: Method used was a retrospective review of data on children presenting to Great Ormond Street Hospital, London, UK, with medulloblastoma, primitive neuroectodermal tumor, atypical teratoid rhabdoid tumor, pilocytic astrocytoma, and ependymoma between 2003 and 2016 inclusive. Uni- and multi-variate analyses were performed to evaluate a range of outcome measures. RESULTS: Three-hundred sixty-one children were identified in total, 53 with disease dissemination at presentation (M:F = 34:19, median age = 3.8 years, range = 7 days-15.6 years) and 308 with solitary tumors (M:F = 161:147, median age = 5.8 years, range = 1 day-16.9 years). Median follow-up was similar irrespective of dissemination status (disseminated tumor 64.0 months, range = 5.2-152.0 months; solitary tumor 74.5 months, range = 4.7-170.1 months; P > 0.05). In multivariate analyses, tumor type and dissemination status at presentation were significantly associated with overall survival (P < 0.0001), risk of recurrence/disease progression (P < 0.01), and event-free survival (P < 0.0001). Subtotal resection was associated with shorter time to recurrence/disease progression (P < 0.01) and worse event-free (P < 0.0001) but not overall survival, whereas treatment with chemotherapy and radiotherapy were associated with improved overall (Ps < 0.0001) and event-free survival (Ps < 0.05). Differences between tumor groups were evident. CONCLUSIONS: Dissemination status at initial presentation significantly affects outcomes in children with CNS tumors.

Clinical and Radiological Predictors of Malignant Middle Cerebral Artery Infarction Development and Outcomes.

BACKGROUND: Optic nerve sheath diameter (ONSD) can predict intracranial hypertension and outcomes in severe traumatic brain injury. Its utility in middle cerebral artery (MCA) stroke is unknown. AIMS: We reviewed serial radiological measurements, including ONSD, in patients with MCA stroke undergoing decompressive craniectomy (DC) for malignant MCA syndrome and compared demographic, clinical, and radiological data with an age- and gender-matched group of nonmalignant MCA stroke patients. METHODS: Patients admitted to a large tertiary hospital in London, UK, between April 2012 and October 2016 with MCA infarction were identified through 2 data sources. We quantified ONSD, eyeball transverse diameter (ETD), ONSD/ETD ratio, midline shift (MLS), and infarct volume on computed tomography (CT). RESULTS: We identified 19 patients (mean age = 49.8 years [standard deviation = 12.5]) with malignant MCA stroke and 19 patients (47.8 years [16.0]) with nonmalignant MCA stroke. Mean ONSD, ONSD/ETD ratio, MLS, and infarct volume on initial CT all significantly increased after developing malignant MCA syndrome and decreased (except infarct volume, which increased) following DC (all Ps <.05). ONSD and ONSD/ETD ratios in the malignant group did not correlate with functional outcomes but were significantly higher on initial CT compared with the nonmalignant group (mean ONSD: 5.66 mm [.6] versus 4.97 mm [.5], P = .001; mean ONSD/ETD ratio: .25 [.03] versus .22 [.02], P = .002). CONCLUSIONS: ONSD, ONSD/ETD ratio, MLS, and infarct volume change dynamically in patients with malignant MCA infarction who undergo DC. An ONSD of more than 5.25 mm and an ONSD/ETD ratio of more than .232 on initial CT may identify MCA stroke patients at high risk of developing malignant MCA syndrome.

Hyponatremia and brain injury: historical and contemporary perspectives.

Hyponatremia is common in neurocritical care patients and is associated with significant morbidity and mortality. Despite decades of research into the syndrome of inappropriate antidiuretic hormone (SIADH) and cerebral salt wasting (CSW), their underlying pathophysiological mechanisms are still not fully understood. This paper reviews the history behind our understanding of hyponatremia in patients with neurologic injury, including the first reports of CSW and SIADH, and current and future challenges to diagnosis and management in this setting. Such challenges include distinguishing CSW, SIADH, and hypovolemic hyponatremia due to a normal pressure natriuresis from the administration of large volumes of fluids, and hyponatremia due to certain medications used in the neurocritical care population. Potential treatments for hyponatremia include mineralocorticoids and vasopressin 2 receptor antagonists, but further work is required to validate their usage. Ultimately, a greater understanding of the pathophysiological mechanisms underlining hyponatremia in neurocritical care patients remains our biggest obstacle to optimizing patient outcomes in this challenging population.

Early years neurosurgical training in the era of the European Working Time Directive.

The past decade has seen significant changes to the face of neurosurgical training in the United Kingdom, driven in part by an increasing focus on patient safety and the introduction of Modernising Medical Careers and the European Working Time Directive (EWTD). Recent reforms to neurosurgical training over the past few years have resulted in creation of an 8-year 'run-through' training programme. In this programme, early years (ST1 and ST2) trainees often lack dedicated time for elective theatre lists and outpatient clinics. Further, any time spent in theatre and clinics is often with different teams. Here we describe a training model for early years trainees at the National Hospital for Neurology and Neurosurgery, who are given the responsibilities traditionally associated with a more senior trainee including dedicated weekly theatre and clinic time under the supervision of a single consultant, in addition to out of hours experience. The advantages and considerations for implementing this model are discussed, including the benefit of guidance under a single consultant in the early stages of training, along with key educational concepts necessary for understanding its utility. We feel that this is an effective model for junior neurosurgical training in the EWTD era, expediting the trainee's development of key technical and non-technical skills, with potentially significant rewards for patient, trainee and trainer. National implementation of this model should be considered.

A systematic review of cognitive interventions for adult patients with brain tumours.

BACKGROUND: Neurocognitive impairments are common in patients with current or previously treated brain tumours, and such impairments can negatively affect patient outcomes including quality of life and survival. This systematic review aimed to identify and describe interventions used to ameliorate (improve) or prevent cognitive impairments in adults with brain tumours. METHODS: We performed a literature search of the Ovid MEDLINE, PsychINFO and PsycTESTS databases from commencement until September 2021. RESULTS: In total, 9998 articles were identified by the search strategy; an additional 14 articles were identified through other sources. Of these, 35 randomised and nonrandomised studies were deemed to meet the inclusion/exclusion criteria of our review and were subsequently included for evaluation. A range of interventions were associated with positive effects on cognition, including pharmacological agents such as memantine, donepezil, methylphenidate, modafinil, ginkgo biloba and shenqi fuzheng, and nonpharmacological interventions such as general and cognitive rehabilitation, working memory training, Goal Management Training, aerobic exercise, virtual reality training combined with computer-assisted cognitive rehabilitation, hyperbaric oxygen therapy and semantic strategy training. However, most identified studies had a number of methodological limitations and were judged to be at moderate-to-high risk of bias. In addition, it remains unclear whether and to what extent the identified interventions lead to durable cognitive benefits after cessation of the intervention. CONCLUSION: The 35 studies identified in this systematic review have indicated potential cognitive benefits for a number of pharmacological and nonpharmacological interventions in patients with brain tumours. Study limitations were identified and further studies should focus on improved study reporting, methods to reduce bias and minimise participant drop-out and withdrawal where possible, and consider standardisation of methods and interventions across studies. Greater collaboration between centres could result in larger studies with standardised methods and outcome measures, and should be a focus of future research in the field.

A Reappraisal of the Pathophysiology of Cushing Ulcer: A Narrative Review.

In 1932, Harvey Cushing described peptic ulceration secondary to raised intracranial pressure and attributed this to vagal overactivity, causing excess gastric acid secretion. Cushing ulcer remains a cause of morbidity in patients, albeit one that is preventable. This narrative review evaluates the evidence pertaining to the pathophysiology of neurogenic peptic ulceration. Review of the literature suggests that the pathophysiology of Cushing ulcer may extend beyond vagal mechanisms for several reasons: (1) clinical and experimental studies have shown only a modest increase in gastric acid secretion in head-injured patients; (2) increased vagal tone is found in only a minority of cases of intracranial hypertension, most of which are related to catastrophic, nonsurvivable brain injury; (3) direct stimulation of the vagus nerve does not cause peptic ulceration, and; (4) Cushing ulcer can occur after acute ischemic stroke, but only a minority of strokes are associated with raised intracranial pressure and/or increased vagal tone. The 2005 Nobel Prize in Medicine honored the discovery that bacteria play key roles in the pathogenesis of peptic ulcer disease. Brain injury results in widespread changes in the gut microbiome in addition to gastrointestinal inflammation, including systemic upregulation of proinflammatory cytokines. Alternations in the gut microbiome in patients with severe traumatic brain injury include colonization with commensal flora associated with peptic ulceration. The brain-gut-microbiome axis integrates the central nervous system, the enteric nervous system, and the immune system. Following the review of the literature, we propose a novel hypothesis that neurogenic peptic ulcer may be associated with alterations in the gut microbiome, resulting in gastrointestinal inflammation leading to ulceration.

Does covid-19 impair endogenous neurogenesis?

Endogenous neural stem cells are thought to continue to generate new neurons throughout life in the human brain. Endogenous neurogenesis has been proposed to contribute to physiological roles in maintaining and regenerating olfaction, as well as promoting normal cognition, learning and memory. Specific impairments in these processes in COVID-19 - impaired olfaction and cognition - may implicate the SARS-CoV-2 virus in attenuating neurogenesis. Furthermore, neurogenesis has been linked with neuroregeneration; and impaired neuroregeneration has previously been linked with neurodegenerative diseases. Emerging evidence supports an association between COVID-19 infection and accelerated neurodegeneration. Also, structural changes indicating global reduction in brain size and specific reduction in the size of limbic structures - including orbitofrontal cortex, olfactory cortex and parahippocampal gyrus - as a result of SARS-CoV-2 infection have been demonstrated. This paper proposes the hypothesis that SARS-CoV-2 infection may impair endogenous neural stem cell activity. An attenuation of neurogenesis may contribute to reduction in brain size and/or neurodegenerative processes following SARS-CoV-2 infection. Furthermore, as neural stem cells are thought to be the cell of origin in glioma, better understanding of SARS-CoV-2 interaction with tumorigenic stem cells is indicated, with a view to informing therapeutic modulation. The subacute and chronic implications of attenuated endogenous neurogenesis are explored in the context of long COVID. Modulating endogenous neurogenesis may be a novel therapeutic strategy to address specific neurological manifestations of COVID-19 and potential applicability in tumour virotherapy.

Arterial and venous thrombotic stroke after ChAdOx1 nCoV-19 vaccine.

Vaccine-induced thrombosis with thrombocytopenia (VITT) is a recently-described condition associated with arterial and venous thrombosis following vaccination with the ChAdOx1 nCoV-19 (AstraZeneca) vaccine. This report describes two cases of stroke caused by arterial and venous thromboses presenting within 28 days of receiving the AstraZeneca vaccine. The patients were otherwise young and healthy with minimal risk factors for thrombosis yet developed a rapid, ultimately fatal neurological deterioration.The patients were significantly thrombocytopenic with disproportionately raised D-dimers, both of which are widely reported in this condition. Both cases had measurable immunoglobulin G platelet factor-4 antibodies detected via enzyme-linked immunosorbent assay, similar to those described in heparin-induced thrombocytopenia.These cases illustrate that physicians should be especially mindful of VITT in the context of evolving evidence on treatment and in view of the potentially rapid and catastrophic neurological deterioration, leading to fatality despite best supportive care.

Influences on cognitive outcomes in adult patients with gliomas: A systematic review.

People with brain tumors, including those previously treated, are commonly affected by a range of neurocognitive impairments involving executive function, memory, attention, and social/emotional functioning. Several factors are postulated to underlie this relationship, but evidence relating to many of these factors is conflicting and does not fully explain the variation in cognitive outcomes seen in the literature and in clinical practice. To address this, we performed a systematic literature review to identify and describe the range of factors that can influence cognitive outcomes in adult patients with gliomas. A literature search was performed of Ovid MEDLINE, PsychINFO, and PsycTESTS from commencement until September 2021. Of 9,998 articles identified through the search strategy, and an additional 39 articles identified through other sources, 142 were included in our review. The results confirmed that multiple factors influence cognitive outcomes in patients with gliomas. The effects of tumor characteristics (including location) and treatments administered are some of the most studied variables but the evidence for these is conflicting, which may be the result of methodological and study population differences. Tumor location and laterality overall appear to influence cognitive outcomes, and detection of such an effect is contingent upon administration of appropriate cognitive tests. Surgery appears to have an overall initial deleterious effect on cognition with a recovery in most cases over several months. A large body of evidence supports the adverse effects of radiotherapy on cognition, but the role of chemotherapy is less clear. To contrast, baseline cognitive status appears to be a consistent factor that influences cognitive outcomes, with worse baseline cognition at diagnosis/pre-treatment correlated with worse long-term outcomes. Similarly, much evidence indicates that anti-epileptic drugs have a negative effect on cognition and genetics also appear to have a role. Evidence regarding the effect of age on cognitive outcomes in glioma patients is conflicting, and there is insufficient evidence for gender and fatigue. Cognitive reserve, brain reserve, socioeconomic status, and several other variables discussed in this review, and their influence on cognition and recovery, have not been well-studied in the context of gliomas and are areas for focus in future research. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42017072976.

VCAM-1-targeted MRI Improves Detection of the Tumor-brain Interface.

PURPOSE: Despite optimal local therapy, tumor cell invasion into normal brain parenchyma frequently results in recurrence in patients with solid tumors. The aim of this study was to determine whether microvascular inflammation can be targeted to better delineate the tumor-brain interface through vascular cell adhesion molecule-1 (VCAM-1)-targeted MRI. EXPERIMENTAL DESIGN: Intracerebral xenograft rat models of MDA231Br-GFP (breast cancer) brain metastasis and U87MG (glioblastoma) were used to histologically examine the tumor-brain interface and to test the efficacy of VCAM-1-targeted MRI in detecting this region. Human biopsy samples of the brain metastasis and glioblastoma margins were examined for endothelial VCAM-1 expression. RESULTS: The interface between tumor and surrounding normal brain tissue exhibited elevated endothelial VCAM-1 expression and increased microvessel density. Tumor proliferation and stemness markers were also significantly upregulated at the tumor rim in the brain metastasis model. T2*-weighted MRI, following intravenous administration of VCAM-MPIO, highlighted the tumor-brain interface of both tumor models more extensively than gadolinium-DTPA-enhanced T1-weighted MRI. Sites of VCAM-MPIO binding, evident as hypointense signals on MR images, correlated spatially with endothelial VCAM-1 upregulation and bound VCAM-MPIO beads detected histologically. These findings were further validated in an orthotopic medulloblastoma model. Finally, the tumor-brain interface in human brain metastasis and glioblastoma samples was similarly characterized by microvascular inflammation, extending beyond the region detectable using conventional MRI. CONCLUSIONS: This work illustrates the potential of VCAM-1-targeted MRI for improved delineation of the tumor-brain interface in both primary and secondary brain tumors.

Perceptions Regarding the SARS-CoV-2 Pandemic's Impact on Neurocritical Care Delivery: Results From a Global Survey.

BACKGROUND: The SARS-CoV-2 (COVID-19) pandemic has impacted many facets of critical care delivery. METHODS: An electronic survey was distributed to explore the pandemic's perceived impact on neurocritical care delivery between June 2020 and March 2021. Variables were stratified by World Bank country income level, presence of a dedicated neurocritical care unit (NCCU) and experiencing a COVID-19 patient surge. RESULTS: Respondents from 253 hospitals (78.3% response rate) from 47 countries (45.5% low/middle income countries; 54.5% with a dedicated NCCU; 78.6% experienced a first surge) participated in the study. Independent of country income level, NCCU and surge status, participants reported reductions in NCCU admissions (67%), critical care drug shortages (69%), reduction in ancillary services (43%) and routine diagnostic testing (61%), and temporary cancellation of didactic teaching (44%) and clinical/basic science research (70%). Respondents from low/middle income countries were more likely to report lack of surge preparedness (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.8-5.8) and struggling to return to prepandemic standards of care (OR, 12.2; 95% CI, 4.4-34) compared with respondents from high-income countries. Respondents experiencing a surge were more likely to report conversion of NCCUs and general-mixed intensive care units (ICUs) to a COVID-ICU (OR 3.7; 95% CI, 1.9-7.3), conversion of non-ICU beds to ICU beds (OR, 3.4; 95% CI, 1.8-6.5), and deviations in critical care and pharmaceutical practices (OR, 4.2; 95% CI 2.1-8.2). Respondents from hospitals with a dedicated NCCU were less likely to report conversion to a COVID-ICU (OR, 0.5; 95% CI, 0.3-0.9) or conversion of non-ICU to ICU beds (OR, 0.5; 95% CI, 0.3-0.9). CONCLUSION: This study reports the perceived impact of the COVID-19 pandemic on global neurocritical care delivery, and highlights shortcomings of health care infrastructures and the importance of pandemic preparedness.

Native nephrectomy for autosomal dominant polycystic kidney disease: before or after kidney transplantation?

UNLABELLED: Study Type - Therapy (case series). LEVEL OF EVIDENCE: 4. What's known on the subject? and What does the study add? The indications and timing of native nephrectomy in patients with autosomal dominant polycystic kidney disease (ADPKD) is controversial, especially for those undergoing renal transplantation. Post-transplant unilateral native nephrectomy appears to be the preferred intervention compared to pre-transplant native nephrectomy. There seems to be substantial additive risk to bilateral over unilateral nephrectomy, especially prior to transplantation. Pre-transplant native nephrectomy should only be carried out when there are clear indications such as massive size preventing allograft placement, severe pain, early satiety, recurrent bleeding and infections, or suspected malignancy. OBJECTIVE: To analyse indications, timing and outcomes of native nephrectomy in autosomal dominant polycystic kidney disease (ADPKD) patients listed for kidney transplantation. PATIENTS AND METHODS: A retrospective analysis of all ADPKD patients who had a native nephrectomy prior to or following transplantation between January 2003 and December 2009 at a single centre, including those undergoing the sandwich technique (removal of the most severely affected native kidney prior to transplantation, and the other afterwards), was undertaken. RESULTS: There were 35 individuals in our cohort (M : F = 16 : 19), with a median age of 51.5 years (range 43-65). Twenty patients were in the pre-transplant nephrectomy group, 12 in the post-transplant group, and three underwent the sandwich technique. Indications for nephrectomy varied but were most commonly pain/discomfort, space for transplantation, ongoing haematuria, recurrent infections, and gastrointestinal pressure symptoms (early satiety). Seven individuals in the pre-transplant group and three in the post-transplant group required critical care admission after nephrectomy. Transient renal graft dysfunction occurred in two post-transplant bilateral nephrectomy patients. Two patients in the bilateral nephrectomy pre-transplant group and one in the bilateral nephrectomy post-transplant group died in the immediate post-operative period. No complications were noted in the sandwich technique group. CONCLUSION: Native nephrectomy in ADPKD is a major undertaking associated with significant morbidity especially in the pre-transplant group. Post-transplant unilateral nephrectomy appears to be the safest approach with fewest complications.