Are Dynamic Arterial Spin-Labeling MRA and Time-Resolved Contrast-Enhanced MRA Suited for Confirmation of Obliteration following Gamma Knife Radiosurgery of Brain Arteriovenous Malformations?

BACKGROUND AND PURPOSE: Intra-arterial DSA has been traditionally used for confirmation of cure following gamma knife radiosurgery for AVMs. Our aim was to evaluate whether 4D arterial spin-labeling MRA and contrast-enhanced time-resolved MRA in combination can be an alternative to DSA for confirmation of AVM obliteration following gamma knife radiosurgery. MATERIALS AND METHODS: In this prospective study, 30 patients undergoing DSA for confirmation of obliteration following gamma knife radiosurgery for AVMs (criterion standard) also underwent MRA, including arterial spin-labeling MRA and contrast-enhanced time-resolved MRA. One dataset was technically unsatisfactory, and the case was excluded. The DSA and MRA datasets of 29 patients were independently and blindly evaluated by 2 observers regarding the presence/absence of residual AVMs. RESULTS: The mean time between gamma knife radiosurgery and follow-up DSA/MRA was 53 months (95% CI, 42-64 months; range, 22-168 months). MRA total scanning time was 9 minutes and 17 seconds. Residual AVMs were detected on DSA in 9 subjects (obliteration rate = 69%). All residual AVMs were detected on at least 1 MRA sequence. Arterial spin-labeling MRA and contrast-enhanced time-resolved MRA showed excellent specificity and positive predictive values individually (100%). However, their sensitivity and negative predictive values were suboptimal due to 1 false-negative with arterial spin-labeling MRA and 2 with contrast-enhanced time-resolved MRA (sensitivity = 88% and 77%, negative predictive values = 95% and 90%, respectively). Both sensitivity and negative predictive values increased to 100% if a composite assessment of both MRA sequences was performed. Diagnostic accuracy (receiver operating characteristic) and agreement (κ) are maximized using arterial spin-labeling MRA and contrast-enhanced time-resolved MRA in combination (area under receiver operating characteristic curve = 1, P < .001; κ = 1, P < .001, respectively). CONCLUSIONS: Combining arterial spin-labeling MRA with contrast-enhanced time-resolved MRA holds promise as an alternative to DSA for confirmation of obliteration following gamma knife radiosurgery for brain AVMs, having provided 100% sensitivity and specificity in the study. Their combined use also enables reliable characterization of residual lesions.

Implementation of duty of candour within neurosurgery: a national survey and framework for improved application in clinical practice.

INTRODUCTION: Statutory duty of candour was introduced in November 2014 for NHS bodies in England. Contained within the regulation were definitions regarding the threshold for what constitutes a notifiable patient safety incident. However, it can be difficult to determine when the process should be implemented. The aim of this survey was to evaluate the interpretation of these definitions by British neurosurgeons. MATERIALS AND METHODS: All full (consultant) members of the Society of British Neurological Surgeons were electronically invited to participate in an online survey. Surgeons were presented with 15 cases and asked to decide in the case of each one whether they would trigger the process of duty of candour. Cases were stratified according to their likelihood and severity. RESULTS: In all, 106/357 (29.7%) members participated in the survey. Responses varied widely, with almost no members triggering the process of duty of candour in cases where adverse events were common (greater than 10% likelihood) and required only outpatient follow-up (7/106; 6.6%), and almost all members doing so in cases where adverse events were rare (less than 0.1% likelihood) and resulted in death (102/106; 96.2%). However, there was clear equipoise in triggering the process of duty of candour in cases where adverse events were uncommon (0.1-10% likelihood) and resulted in moderate harm (38/106; 35.8%), severe harm (57/106; 53.8%) or death (49/106; 46.2%). CONCLUSION: There is considerable nationwide variation in the interpretation of definitions regarding the threshold for duty of candour. To this end, we propose a framework for the improved application of duty of candour in clinical practice.

Long-term agroecosystem research in the central Mississippi river basin: dissolved nitrogen and phosphorus transport in a high-runoff-potential watershed.

Long-term monitoring data from agricultural watersheds are needed to determine if efforts to reduce nutrient transport from crop and pasture land have been effective. Goodwater Creek Experimental Watershed (GCEW), located in northeastern Missouri, is a high-runoff-potential watershed dominated by claypan soils. The objectives of this study were to: (i) summarize dissolved NH-N, NO-N, and PO-P flow-weighted concentrations (FWC), daily loads, and yields (unit area loads) in GCEW from 1992 to 2010; (ii) assess time trends and relationships between precipitation, land use, and fertilizer inputs and nutrient transport; and (iii) provide context to the GCEW data by comparisons with other Corn Belt watersheds. Significant declines in annual and quarterly FWCs and yields occurred for all three nutrient species during the study, and the decreases were most evident for NO-N. Substantial decreases in first- and fourth-quarter NO-N FWCs and daily loads and modest decreases in first-quarter PO-P daily loads were observed. Declines in NO-N and PO-P transport were attributed to decreased winter wheat ( L.) and increased corn ( L.) production that shifted fertilizer application from fall to spring as well as to improved management, such as increased use of incorporation. Regression models and correlation analyses indicated that precipitation, land use, and fertilizer inputs were critical factors controlling transport. Within the Mississippi River Basin, NO-N yields in GCEW were much lower than in tile-drained areas, but PO-P yields were among the highest in the basin. Overall, results demonstrated that reductions in fall-applied fertilizer and improved fertilizer management reduced N and P transport in GCEW.

Long-term agroecosystem research in the central Mississippi river basin: goodwater creek experimental watershed and regional nutrient water quality data.

We document the 20-yr-long research effort to study the transport of N and P to surface and groundwater in Goodwater Creek Experimental Watershed. We also document related efforts in nearby claypan watersheds and watersheds with contrasting soil and hydrologic conditions across the northern Missouri-southern Iowa region. Details of the analytical methods, instrumentation, method detection limits, and quality assurance program used to generate the data are described along with a brief overview of significant findings. Nutrient concentrations in streams were in the range associated with nuisance algal growth and presumed loss of aquatic invertebrate diversity. Incorporation of fertilizers was shown to be the most effective practice for reducing nutrient transport in runoff. Despite the claypan soils, NO leaching was a major fate for fertilizer N, and significant contamination of the glacial till aquifer has occurred when long-term fertilizer and manure N inputs exceeded crop N requirements. A key finding of these studies was that field areas with the poorest crop growth were also the most vulnerable to nutrient as well as sediment and herbicide transport.

Angiogram negative subarachnoid haemorrhage: outcomes and the role of repeat angiography.

BACKGROUND: Angiogram negative sub-arachnoid haemorrhage (SAH) is generally considered to have a more benign course than SAH of known cause. There is also variability from centre to centre as to what proportion of angiogram negative SAH patients undergo repeat Digital Subtraction Angiography (DSA). We performed a retrospective study looking at the last four years' of SAH patients at our institution in order to ascertain the clinical course, the nature and results of repeat imaging. METHODS: Retrospective analysis of clinical records and imaging of all patients presenting to our institution with non-traumatic SAH between April 2008 and February 2012 was performed. Results were analysed for presenting grades, blood distribution, complications, outcomes, repeat imaging modalities and findings. RESULTS: 459 patients with proven non-traumatic SAH of which 50 (11%) had no vascular cause identified on their initial angiogram were identified. The blood distribution was perimesencephalic in 17, non-perimesencephalic in 23, and 10 patients were computed tomography (CT) Negative with a positive lumbar puncture. Eight (16%) patients were complicated by hydrocephalus and 2 (4%) were complicated by vasospasm. Eight patients (16%) underwent repeat cranial DSA with a high suspicion in a multi-disciplinary team setting. None of the repeat angiograms showed an underlying aetiology for the SAH. 76% of patients had a Glasgow Outcome Score of 5 at 6 months. There were no rebleeds. CONCLUSIONS: While generally more benign, angiogram negative subarachnoid haemorrhage can have a complicated clinical course. In our experience repeat DSA should be reserved for cases in which there is significant suspicion of occult vascular lesion. However, evidence-based guidelines are needed to aid the development of management protocols for angiogram-negative SAH and ensuring optimal patient outcomes.

Spontaneous pneumocephalus presenting with alien limb phenomena.

BACKGROUND: Spontaneous pneumocephalus is a rare condition that has been reported infrequently. Alien limb syndrome is an uncommon phenomenon most often seen in patients with frontal and callosal lesions. METHOD: Case report of a patient with pneumocephalus presenting with alien limb syndrome. The patient underwent successful surgical management. A literature review and discussion of aspects of this presentation are also included. CONCLUSION: In this case, a spontaneous pneumocephalus has formed a frontal space-occupying lesion and presented with alien limb phenomena.

The longitudinal profile of bilirubin and ferritin in the cerebrospinal fluid following a subarachnoid hemorrhage: diagnostic implications.

BACKGROUND: Cerebrospinal fluid (CSF) spectrophotometry for bilirubin is a highly sensitive test in the diagnostic work up of a suspected subarachnoid hemorrhage (SAH). CASES: We report two cases suffering from an aneurysmal SAH in which extraventricular drainage for acute hydrocephalus was required. Longitudinal analyses of the CSF samples demonstrated that CSF bilirubin was detectable in all cases during the first week, becoming undetectable in one case in the second week. Importantly, CSF ferritin levels rose substantially (>1,000 ng/ml) after 6 days, peaking around 3,000 ng/ml after 2 weeks (normal upper reference range 12 ng/ml). In both cases blood was visible on the initial CT brain scan, disappearing on a later scan. CONCLUSION: CSF ferritin levels may be an important additional laboratory test in the diagnostic work-up of patients with a suspected SAH. CSF ferritin levels may prove particularly helpful in cases with late presentation if the CT brain scan is normal and CSF bilirubin level is undetectable.

The longitudinal profile of CSF markers during external lumbar drainage.

BACKGROUND: External lumbar drainage (ELD) is known as a good predictor of favourable outcome in shunting patients suffering from idiopathic normal pressure hydrocephalus (iNPH). METHODS: Eleven patients suffering from iNPH had a lumbar drain (LD) inserted for 72 h and participated in a research study to quantify any improvement in their clinical symptoms. The lumbar cerebrospinal fluid (CSF) levels of lactate, 8-isoprostane, vascular endothelial growth factor (VEGF), glial fibrillar acidic protein (GFAP), neurofilament (heavy chain) protein (NF (h)), Abeta(1-42) (beta-amyloid) and total tau were assayed samples from all three time points. RESULTS: The concentrations of lactate, VEGF, GFAP and tau increased significantly during the 72 h of drainage. There were also increases in 8-isoprostane and Abeta(1-42) (non significant). The concentration of NF (h) was reduced significantly following 72 h of drainage. There was a significant positive correlation between Abeta(1-42) and total tau in the first sample. GFAP was negatively correlated in a significant fashion with both Abeta(1-42) and total tau. NF (h) was negatively correlated with VEGF. CONCLUSION: Evidence is provided that ELD is producing measurable changes in the CSF composition of patients with iNPH. The present paper discusses how such changes may be implicated in the pathophysiology of the condition.

Improving the recovery of S100B protein in cerebral microdialysis: implications for multimodal monitoring in neurocritical care.

INTRODUCTION: Cerebral microdialysis is an established research tool that is used by an increasing number of neurocritical care units as a component of bedside multimodality monitoring. Body fluid biomarkers are an emerging tool for the assessment of brain injury. The correct interpretation of body fluid biomarker levels depends on the degree of recovery, i.e. relative recovery and the accuracy of the analytical technique. METHODS: In vitro recovery experiments were performed on 100mL volumes of cerebrospinal fluid and solutions of S100B, glucose, lactate and pyruvate comparing relative recoveries using commercially available 20 kDa (CMA70) and 100 kDa (CMA71) microdialysis catheters. We also compared the CMA 600 microdialysis analyzer with a YSI 2003 STAT Plus analyzer for glucose and lactate to determine its reliability. RESULTS: Significantly, we demonstrate the improved recovery of the protein S100B using a larger molecular weight (MW) cut-off catheter (20 kDa range: 0.1-9%; 100 kDa range: 1.7-18.3%) while maintaining comparable performance for the conventional markers glucose, lactate and pyruvate. Additionally we found that the CMA 600 analyzer may be prone to overestimation of lactate readings at higher concentration with implications for clinical decision-making. CONCLUSION: Our data demonstrates that the 100 kDa MW cut-off catheter allows for the improved recovery of macromolecules in cerebral microdialysis research while maintaining the value of existing MD data for routine clinical use.

Development of cavernous haemangioma following radical chemo-radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: We report an adult case of nasopharyngeal carcinoma treated with radical chemo-radiotherapy, with subsequent development of a histologically proved temporal cavernous haemangioma within the radiation field. METHOD: Case report and review of the current literature concerning radiation-induced, secondary, space-occupying lesions. CONCLUSION: The increasing role of radiotherapy in nasopharyngeal carcinoma treatment, together with improved patient survival, is likely to lead to radiation-induced, secondary, space-occupying lesions being encountered more frequently. We emphasise the need to be vigilant for this important but relatively rare complication, which has significant associated morbidity.

Does conservative management for brain stem cavernomas have better long-term outcome?

There has been a controversy in the last 15 years on the correct management of brain stem cavernomas. We have reviewed our experience of the last 10 years in a single Institution and reviewed related literature published in the last 15 years. We recorded the demographics, clinical presentation, rebleeding episodes, incidence of neurological events and outcome assessed by recording the change of the modified Rankin scale in 21 cases. Univariate analysis was applied to test the effect of demographics, and presentation on the incidence and timing of rebleeding, chance of having a new neurological event, the number of subsequent neurological events and outcomes. Six cases were treated with surgery and 15 cases were managed conservatively. We obtained follow-up data in 20 patients (95%). Mean follow-up period was 79.7 months (range: 6-244, median 70 months). There were 0.05 rebleeding events per patient-year and 0.1 episodes of neurological deterioration per patient-year. No mortality was noted in either the surgical or the non-surgical group. Three of the six surgical cases had a reoperation. The outcome was improved in one patient, unchanged in 1, and worse in 3 surgical patients. In the case of conservative management the outcome was improved in two patients, unchanged in five patients, and worse in eight patients. Outcome was worse in the case of multiple cavernomas (p = 0.012). Our findings suggest that conservative management may be appropriate in individual cases when compared with surgery, but this difference was not statistically significant enough in order to support a change in practice. The natural history of brain stem cavernomas appears more benign than previously thought.

Metabolic failure precedes intracranial pressure rises in traumatic brain injury: a microdialysis study.

BACKGROUND: Cerebral microdialysis (MD) is able to detect markers of tissue damage and cerebral ischaemia and can be used to monitor the biochemical changes subsequent to head injury. In this prospective, observational study we analysed the correlation between microdialysis markers of metabolic impairment and intracranial pressure (ICP) and investigated whether changes in biomarker concentration precede rises in ICP. METHODS: MD and ICP monitoring was carried out in twenty-five patients with severe TBI in Neurointensive care. MD samples were analysed hourly for lactate:pyruvate (LP) ratio, glutamate and glycerol. Abnormal values of microdialysis variables in presence of normal ICP were used to calculate the risk of intracranial hypertension developing within the next 3 h. FINDINGS: An LP ratio >25 and glycerol >100 micromol/L, but not glutamate >12 micromol/L, were associated with significantly higher risk of imminent intracranial hypertension (odds ratio: 9.8, CI 5.8-16.1; 2.2, CI 1.6-3.8; 1.7, CI 0.6-3, respectively). An abnormal LP ratio could predict an ICP rise above normal levels in 89% of cases, whereas glycerol and glutamate had a poorer predictive value. CONCLUSIONS: Changes in the compound concentrations in microdialysate are a useful tool to describe molecular events triggered by TBI. These changes can occur before the onset of intracranial hypertension, suggesting that biochemical impairment can be present before low cerebral perfusion pressure is detectable. This early warning could be exploited to expand the window for therapeutic intervention.

Free phenytoin concentration measurement in brain extracellular fluid: a pilot study.

This article investigates the relationship between brain extracellular fluid free phenytoin concentration and plasma free phenytoin concentration in adults with acute brain injury. Daily cerebral microdialysate free phenytoin concentration was measured in eight adults with acute brain injury and compared with simultaneous measurement of plasma free phenytoin concentration. The group data revealed no significant correlation between microdialysate and plasma free phenytoin concentration (r = 0.34, p = 0.41). However, in two patients, with a sufficient number of samples for intra-individual analysis, there was a significant correlation between microdialysate and plasma free phenytoin concentration (r = 0.92, p < 0.001 and r = 0.88, p < 0.01). In vitro microdialysis relative recovery for phenytoin was 2.1%. In the context of acute brain injury, measurement of free plasma phenytoin concentration may not provide an accurate reflection of regional brain extracellular fluid free phenytoin concentration and may have limitations with respect to achieving reproducible brain extracellular fluid free phenytoin concentrations. This has implications for dosing regimens relying on plasma phenytoin levels.

The interleukin-6 gene -174G>C and -572G>C promoter polymorphisms are related to cerebral aneurysms.

BACKGROUND AND AIMS: An important part is played by inflammation in intracranial aneurysm formation. The hypothesis that there is an association of the proinflammatory cytokine interleukin-6 (IL-6) genotypes (-572G>C and -174G>C) with intracranial aneurysms was tested. METHODS: IL-6 genotypes were determined in 91 Caucasian patients with aneurysms and compared with 2720 healthy UK controls. RESULTS: For both polymorphisms, the distribution of the genotypes and estimated allele frequency were different between the control group and the aneurysm group. For -572G>C, a higher frequency of the C allele (p = 0.001) and more people homozygous for the C allele were found among those with aneurysms than among the controls (4.4% v 0.3%, p = 0.001). For -174G>C, more people homozygous for the C allele were found among the controls than among those with aneurysm (18% v 7%, p = 0.007). The 572C/174G haplotype was associated with an increased risk of aneurysms, with the relative risk compared with the common haplotype being 1.89 and that for the -572G/174C haplotype being 0.58 (p<0.0005). CONCLUSION: This is the first study to show that IL-6 promoter polymorphisms are associated with intracranial aneurysmal disease. Whether this association is with the development, progression or rupture of such aneurysms, or represents survivor bias, is unclear.

Mixed glioneuronal tumour of the fourth ventricle with prominent rosette formation.

We describe three unusual tumours characterized by a mixture of glial and neuronal differentiation, involvement of the posterior fossa and formation of rosettes. Mixed glial-neuronal tumours of the posterior fossa are rare and poorly described neoplasms. However, several distinctive entities have appeared in the literature over recent years under a variety of different names. Our cases demonstrate the morphological features of the 'rosette-forming glioneuronal tumour of the fourth ventricle', a recently identified tumour characterised by its unique location, neurocytic pseudo-rosette formation and the presence of a low grade astrocytoma component. The long term prognosis of these tumours remains unclear. However, the clinical data available including the cases presented here, along with the histological features, suggest that these are low grade tumours with a good prognosis after surgical resection.