The use of cerebral computed tomographic angiography as an ancillary investigation to support a clinical diagnosis of death using neurological criteria: a consensus guideline.

This multidisciplinary consensus statement was produced following a recommendation by the Faculty of Intensive Care Medicine to develop a UK guideline for ancillary investigation, when one is required, to support the diagnosis of death using neurological criteria. A multidisciplinary panel reviewed the literature and UK practice in the diagnosis of death using neurological criteria and recommended cerebral CT angiography as the ancillary investigation of choice when death cannot be confirmed by clinical criteria alone. Cerebral CT angiography has been shown to have 100% specificity in supporting a diagnosis of death using neurological criteria and is an investigation available in all acute hospitals in the UK. A standardised technique for performing the investigation is described alongside a reporting template. The panel were unable to make recommendations for ancillary testing in children or patients receiving extracorporeal membrane oxygenation.

Brainstem cavernous malformations - no longer a forbidden territory? A systemic review of recent literature.

BACKGROUND: Due to its eloquent location and potentially devastating neurological consequences, the management of brainstem cavernous malformations (CCMs) attracts considerable debate. There is currently a paucity of Level 1 evidence for their management. The aim of this literature review is to explore the current evidence on the risk-benefit profile of different management options. METHODS: A systemic literature search, following the PRISMA algorithm was performed on publications between 2010 and 2018 using the Pubmed database, with the relevant keywords. Only English articles were included. Articles focusing on spinal CCMs and studies with less than 30 participants were excluded. RESULTS: A total of 222 search results were reviewed and after removal of duplicates and screening of abstracts, 28 clinical papers comprising 30 or more brainstem CCM cases were included in the study. The heterogeneity of the publications precluded a formal meta-analysis of results. The general consensus is that for CCMs presenting with severe symptoms and/or multiple haemorrhages that reach an accessible pial surface, surgery is considered to be the gold-standard treatment, with some authors suggesting the optimal timing to be within two to six weeks of ictus. For those patients with multiple, deep-seated CCM related haemorrhages that do not reach the pial surface, stereotactic radiosurgery (SRS) can be considered. Conservative treatment is generally considered in incidental cases. Management of brainstem cavernomas of other categories still remains controversial. CONCLUSIONS: Due to their highly eloquent location, brainstem CCMs are challenging lesions to manage. Management must be balanced by the risk-benefit profile and tailored to the individual patients and their treating clinicians. This review provides a comprehensive reference considering all treatment options and provides a basis for evidence-based patient counselling.

An association between cerebral aneurysm re-bleed and CT angiography--more than a coincidence?

Rupture of cerebral aneurysm during CT angiogram is a rare occurrence. Here we present such a case where an aneurysmal re-rupture during CT angiogram was demonstrated.

Metastatic adenocarcinoma masquerading as a solitary nerve sheath tumour.

We present a case of a solitary metastasis of an adenocarcinoma to a dorsal root ganglion (DRG) following a disease free interval of 12 years after resection of a Duke's C carcinoma. The presentation of this unusually placed metastasis was associated with a 3-year complex pain syndrome and radiological appearances consistent with benign disease. The case highlights the importance of not dismissing unusual lesions as innocent in the presence of a history of malignant disease.

Timing of surgery for aneurysmal subarachnoid haemorrhage.

BACKGROUND: The timing of surgery to secure a ruptured aneurysm after a subarachnoid haemorrhage is an important issue. Early clipping of an aneurysm prevents rebleeding, a major cause of death after a subarachnoid haemorrhage. However, concerns about the possible deleterious effects of early surgery raise questions about the safety and efficacy of this approach. This review examines the randomised controlled evidence addressing the effect of surgery at different time intervals on the outcome after a subarachnoid haemorrhage. OBJECTIVES: To determine whether the timing of surgery after a subarachnoid haemorrhage significantly influences overall management outcome. SEARCH STRATEGY: We searched the Cochrane Stroke Review Group Trials Register and in addition searched MEDLINE, EMBASE and the Cochrane Controlled Trials Register (CENTRAL/CCTR). Colleagues were contacted to identify further studies and unpublished trials. SELECTION CRITERIA: All completed, unconfounded, truly randomised trials comparing "best medical treatment plus early surgery" with "best medical treatment plus delayed surgery". DATA COLLECTION AND ANALYSIS: The authors selected trials for inclusion, or exclusion, according to the above criteria. An "intention to treat" analysis strategy was utilised. MAIN RESULTS: Only one randomised controlled trial addressing the timing of surgery after aneurysmal subarachnoid haemorrhage was identified. Patients undergoing early surgery tended to fare better than those undergoing late surgery (death or dependency at 3 months OR 0.37 95% CI 0.13,1.02). Patients undergoing surgery in the intermediate time period appeared to fare worse than those undergoing early surgery although confidence intervals were wide (death or dependency at 3 months OR 0.34 95% CI 0.12, 0.93). REVIEWER'S CONCLUSIONS: Based upon the limited randomised controlled evidence available, the timing of surgery was not a critical factor in determining outcome following a subarachnoid haemorrhage. Since the publication of the only randomised controlled study in 1989, techniques for the treatment of subarachnoid haemorrhage have progressed, questioning the validity of the conclusions in the modern era. Currently, most neurovascular surgeons elect to operate within 3 or 4 days of the bleed in good grade patients to minimise the chances of a devastating rebleed. However, the treatment of patients in poorer grades warrants further scrutiny in a randomised controlled trial.

Age dependence of cerebrospinal pressure-volume compensation in patients with hydrocephalus.

OBJECT: The dynamics of both drainage and storage capacity become altered during the sequential pathological processes that lead to hydrocephalus. Cerebrospinal fluid (CSF) formation and drainage rate have been reported to be age dependent. The aim of this study was to investigate whether CSF compensatory parameters are dependent on age in patients who have symptoms of hydrocephalus and apparently normal intracranial pressure (ICP). METHODS: Forty-six patients who presented with ventriculomegaly, the clinical symptoms of hydrocephalus, and normal ICPs underwent a computerized CSF infusion test. Parameters used to describe CSF compensation were calculated and correlated with the age of each patient. The mean ICPs were found to be independent of the age of the patient. Resistance to CSF outflow (Rcsf), however, demonstrated a nonlinear increase with advancing age (r = -0.57; p < 0.0001) and was associated with a decrease in the CSF production rate, which also occurred with increasing age (r = 0.49; p < 0.002). Both the pulse amplitude of the ICP waveform and the slope of the amplitude-ICP regression line increased significantly with advancing age (r = 0.39; p < 0.01 and r = 0.43, p < 0.004, respectively). The nonlinear increase in the elastance coefficient indicated increasing brain stiffness, which acompanies older ages (r = -0.31; p < 0.04). CONCLUSIONS: In a study of patients with symptoms of hydrocephalus, but normal ICPs, the increase in Rcsf and decrease in CSF production were most pronounced in patients who were older than 56 years of age. This relationship was more significant than previously suggested.

Preliminary experience of the estimation of cerebral perfusion pressure using transcranial Doppler ultrasonography.

OBJECTIVE: The direct calculation of cerebral perfusion pressure (CPP) as the difference between mean arterial pressure and intracranial pressure (ICP) produces a number which does not always adequately describe conditions for brain perfusion. A non-invasive method of CPP measurement has previously been reported based on waveform analysis of blood flow velocity measured in the middle cerebral artery (MCA) by transcranial Doppler. This study describes the results of clinical tests of the prototype bilateral transcranial Doppler based apparatus for non-invasive CPP measurement (nCPP). METHODS: Twenty five consecutive, paralysed, sedated, and ventilated patients with head injury were studied. Intracranial pressure (ICP) and arterial blood pressure (ABP) were monitored continuously. The left and right MCAs were insonated daily (108 measurements) using a purpose built transcranial Doppler monitor (Neuro Q(TM), Deltex Ltd, Chichester, UK) with software capable of the non-invasive estimation of CPP. Time averaged values of mean and diastolic flow velocities (FVm, FVd) and ABP were calculated. nCPP was then computed as: ABPxFVd/FVm+14. RESULTS: The absolute difference between real CPP and nCPP (daily averages) was less than 10 mm Hg in 89% of measurements and less than 13 mm Hg in 92% of measurements. The 95% confidence range for predictors was no wider than +/-12 mm Hg (n=25) for the CPP, varying from 70 to 95 mm Hg. The absolute value of side to side differences in nCPP was significantly greater (p<0.05) when CT based evidence of brain swelling was present and was also positively correlated (p<0.05) with mean ICP. CONCLUSION: The device is of potential benefit for intermittent or continuous monitoring of brain perfusion pressure in situations where the direct measurement is not available or its reliability is in question.

Bifrontal decompressive craniectomy in the management of posttraumatic intracranial hypertension.

Bifrontal decompressive craniectomy has been used on an ad hoc basis for the treatment of post-traumatic intracranial hypertension for more than thirty years. In this observational study we report the clinical outcome and physiological effects of the procedure in a series of 26 patients with refractory intracranial hypertension treated on a protocol driven basis. Bifrontal decompressive craniectomy was associated with significant reductions in mean ICP from 37.5 to 18.1 mmHg (p = 0.003). In addition, craniectomy reduced the amplitude of ICP waves (p < 0.02) and increased compensatory reserve (p < 0.05). A favourable outcome was achieved in 69% of patients; 8% were severely disabled and 23% died. We conclude that this study provides pathophysiological evidence that bifrontal decompressive craniectomy significantly reduces posttraumatic intracranial hypertension and improves pressure dynamics. Our results support the continued use of bifrontal decompressive craniectomy in selected patients after head injury.

Cerebral venous blood outflow: a theoretical model based on laboratory simulation.

OBJECTIVE: The cerebrovascular bed and cerebrospinal fluid circulation have been modeled extensively except for the cerebral venous outflow, which is the object of this study. METHODS: A hydraulic experiment was designed for perfusion of a collapsible tube in a pressurized chamber to simulate the venous outflow from the cranial cavity. CONCEPT: The laboratory measurements demonstrate that the majority of change in venous flow can be attributed to either inflow pressure when the outflow is open, or the upstream transmural pressure when outflow is collapsed. On this basis, we propose a mathematical model for pressure distribution along the venous outflow pathway depending on cerebral blood flow and intracranial pressure. The model explains the physiological strong coupling between intracranial pressure and venous pressure in the bridging veins, and we discuss the limits of applicability of the Starling resistor formula to the venous flow rates. The model provides a complementary explanation for ventricular collapse and origin of subdural hematomas resulting from overshunting in hydrocephalus. The noncontinuous pressure flow characteristic of the venous outflow is pinpointed as a possible source of the spontaneous generation of intracranial slow waves. CONCLUSION: A new conceptual mathematical model can be used to explain the relationship between pressures and flow at the venous outflow from the cranium.

Expression of the immediate early genes c-Fos and c-Jun after head injury in man.

Immediate early genes (IEC) are expressed in a variety of experimental paradigms including cerebral ischemia and trauma. There is a paucity of information on whether the results of laboratory experiments can be extrapolated from animals into man. To examine this further we hypothesized that expression of c-Fos and c-Jun occurs after contusional head injury in man. We also sought to identify whether there was an association between the level of immediate early gene expression and 1. the outcome one year after head injury, 2. the timing of surgery after head injury. IEG expression was examined using in situ hybridization and immunocytochemistry in brain tissue therapeutically removed in 14 patients with head injury 6 h to 6 days after contusional injury. IEG expression was also examined in tissue removed during elective non-traumatic neurosurgery for comparative purposes. Expression of c-fos and c-jun mRNA was observed in 50% and 64% of head-injured patients respectively. Protein immunoreactivity for these IEGs was evident in 67% of head injured patients. The expression of c-Fos and c-Jun was associated with final outcome. Patients with poorer outcomes had higher levels of gene expression (p = 0.08 for c-Fos and p = 0.006 for c-Jun). No correlation between the timing of surgery and the intensity of gene expression was evident in the trauma patients (r2 = 0.09 and 0.10 for c-Fos and c-Jun respectively). In the non-trauma patients 36% expressed c-fos and 73% expressed c-jun mRNA, with all patients studied expressing c-Fos and c-Jun proteins. We conclude that differential expression of c-Fos and c-Jun occurs in the patients with cerebral contusions. The difference in expression rates between mRNA and protein emphasises the need for analysis of gene products when investigating gene expression. These results support the hypothesis that IEGs may be involved in the pathogenetic mechanisms of contusional head injury. Observations of IEG expression in human brain injury are important in steering animal experimental programmes towards studies that may yield information directly applicable to human brain injury.

Delayed induction of JunB precedes CA1 neuronal death after global ischemia in the gerbil.

The immediate early genes (IEGs), c-jun, junB and c-fos are expressed after global ischemia in the gerbil. The role of these genes remains unclear. Whilst moderate ischemia (7 min) causes delayed CA1 neuronal death, pre-conditioning with mild ischemia (2 min) neuroprotects the CA1 subfield. This differential response allows the specific expression patterns of IEGs to be associated with either delayed neuronal death, or cell survival, depending upon the insult severity. Using a graded insult strategy we have shown that (1) early IEG expression is prominent in the neuronal layers of the CA3, hilar and dentate regions, and (2) a delayed, secondary wave of JunB expression is localized to the selectively vulnerable CA1 neuronal layer after moderate ischemia. This expression precedes the histological and histochemical features of neuronal death. Delayed JunB expression was not observed in animals subject to 2 min ischemia. The glial fibrillary acidic protein (GFAP) promotor possesses an AP-1 binding site, the target for IEG dimers. To examine the possible link between IEG expression and astrocyte activation the transcriptional activation of GFAP was assessed. GFAP mRNA was evident within 8 h of ischemia after both insults. The extent of the astrocytic reaction was dependent upon the severity of the ischemia. The temporospatial distribution of IEG and GFAP expression differed, indicating that glial activation is unlikely to be regulated by the hippocampal expression of IEGs. We conclude that early IEG expression is involved in signalling mechanisms that invoke neuroprotective effects in the dentate and CA3 regions, and that delayed JunB expression in the CA1 subfield is associated with neuronal death, and may be involved in the commitment or execution phases of cell death. Early astrocytic responses may play a role in the mechanism of ischaemic tolerance.

The surgical management of patients with glomus tumours of the skull base.

Total surgical excision is the only treatment modality that offers a cure for patients with glomus tumours of the skull base. The vascularity, inaccessibility and frequently extensive local spread, all contribute to the difficulties encountered in the management of patients with these complex lesions. Owing to the rarity of skull base glomus tumours, experience in their management can only be attained over long periods of time. We describe the surgical management of 20 patients with large glomus tumours of the skull base treated by an otoneurosurgical team over an 11-year period. Overall, 70% of patients had an excellent outcome, 10% a good outcome and 20% a poor outcome at a mean follow-up of 3.1 years. Poor outcomes were due to severe facial nerve palsies in two cases, and poorly accommodated palsies of the bulbar cranial nerves in a further two patients. The management of postoperative neurological deficits is discussed in detail. We conclude that in the majority of patients with skull base glomus tumours, complete surgical excision can be safely achieved.

An audit of aneurysmal subarachnoid haemorrhage: earlier resuscitation and surgery reduces inpatient stay and deaths from rebleeding.

OBJECTIVE: To audit the outcome in patients with subarachnoid haemorrhage (SAH) after a change in management strategy. METHODS: A retrospective analysis of patients with aneurysmal subarachnoid haemorrhage over a 20 month period (phase 1) was followed by a prospective analysis of patients presenting during the next 20 months (phase 2) in which a protocol driven management regime of immediate intravenous fluid resuscitation and earlier surgery was pursued. Patients in this phase were grouped into those receiving early (within four days of subarachnoid haemorrhage) and late (after four days of subarachnoid haemorrhage) surgery. In phase 1, 75 out of a total of 92 patients underwent surgery on (median) day 12. From phase 2, 109 patients out of a total of 129 underwent surgery on (median) day 4, 58 of which had their surgery within 4 days of the subarachnoid haemorrhage. Patients in each phase/group were well matched for demographic features, site of aneurysm, and severity of subarachnoid haemorrhage. RESULTS: The surgical morbidity and mortality were no different in the two phases (P < 0.92; chi2 test). The management outcomes in the two phases of the study were also no different (P < 0.52). However, there was a significant reduction in the rebleed rate in patients undergoing surgery within four days of the subarachnoid haemorrhage in phase 2 (P < 0.0001) with an associated trend towards reduced incidence of postoperative ischaemia (P = 0.06) and mortality (P = 0.11). Operating earlier in phase 2 of the trial resulted in a lower total hospital inpatient stay of 15.8 (95% CI 13.1-18.5) days for survivors compared with 25.7 (95% CI 21.6-29.8) days in the late group (P < 0.00001; t test). CONCLUSIONS: surgical morbidity and mortality seemed independent of the timing of aneurysm surgery. Early surgery within four days was associated with a highly significant reduction in rebleed rate, and in the duration of total hospital inpatient stay.

Safe removal of retained ventricular catheters using intraluminal choroid plexus coagulation. Technical note.

The authors describe a simple technique that reduces the incidence of retained ventricular catheters and minimizes the risk of life-threatening intraventricular hemorrhage during the removal of an obstructed, adherent ventricular catheter in patients with hydrocephalus. The technique requires no special equipment and has been successfully used, without complications, in a prospective series of 12 patients with 13 blocked, adherent ventricular catheters.

An observational study of near-infrared spectroscopy during carotid endarterectomy.

Near-infrared spectroscopy was used to monitor changes in the cerebral oxygenation state in 13 patients during carotid endarterectomy. Variations in the levels of the chromophores (oxygenated hemoglobin (HbO2), deoxygenated hemoglobin (Hb), and oxidized cytochrome (CytO2)), and the total hemoglobin content (tHb) were compared with changes in middle cerebral artery flow velocity measured using transcranial Doppler ultrasonography. Of eight patients who showed a fall in flow velocity on application of the internal carotid artery cross-clamp, seven demonstrated a rapid and closely correlated fall in HbO2 signal, and an increase in Hb. Levels of CytO2 and tHb remained unchanged. During endarterectomy, recovery of the HbO2 and Hb levels toward preclamp baseline values occurred in three of these patients. Intraoperative shunts accelerated recovery of HbO2 and Hb signals in two of three individuals. Release of the internal carotid cross-clamp resulted in a rapid increase in HbO2 and decrease in Hb signal in those patients in whom spontaneous recovery had not occurred; in five instances, a hyperemia evolved with raised flow velocity and HbO2 to above baseline values. Cross-clamping and subsequent reperfusion of the external carotid artery had no effect on any parameter measured. The authors conclude that near-infrared spectroscopy can register changes in cerebral oxygenation during carotid endarterectomy without significant contamination from extracranial tissues.

Nimodipine.

Nimodipine is a lipophilic dihydropyridine calcium antagonist which is used to reduce the incidence and severity of delayed cerebral ischaemia in patients with subarachnoid haemorrhage. This article reviews its mechanism of action, pharmacology and indications for use.