Endoscopic Petrous Apex Surgery: The Utilization of Frontal Sinus Instrumentation.

BACKGROUND: The petrous apex is a complex anatomic region for which each surgical approach each has distinct limitations. The authors describe the use of frontal sinus instrumentation for the endonasal endoscopic approach to petrous apex lesions OBJECTIVE:: To demonstrate that the angled design of frontal sinus instrumentation has pronounced clinical utility for the transsphenoidal transclival approach to the petrous apex. METHODS: The authors present cases of expansile petrous apex lesions approached endoscopically via transsphenoid and transclival corridors, and highlight the technique of using curved frontal sinus instruments and angled endoscopes for posterolateral reach in the petrous apex dissection. RESULTS: As demonstrated in the accompanying video, dissection with frontal sinus instrumentation allows the surgeon to navigate around the internal carotid artery. CONCLUSIONS: Significant technical and technological advances have been made in the field of expanded endoscopic endonasal skull base surgery in the past 3 decades. Increasing efforts are made to push the boundaries and access more laterally located lesions, such as those in the petrous apex. Surgical trajectory or vector is paramount to safely navigate around the internal carotid artery.

Transoral Finger-Retraction for Endonasal Endoscopic Resection of Masseteric and Buccal Space Lesions.

Lesions involving the masseteric and buccal spaces have traditionally required transoral or transcervical approaches. Herein, the authors describe the successful endonasal endoscopic resection of a juvenile nasopharyngeal angiofibroma (JNA) with significant extension into the masseteric and buccal spaces facilitated by transoral finger retraction. Juvenile nasopharyngeal angiofibromas are hypervascular tumors originating in the pterygopalatine fossa (PPF) with complex relationships to skull base and orbital structures. Endoscopic approaches have allowed for resection of JNAs with excellent visualization and without traditional transfacial approaches, decreasing morbidity and reducing incidence of facial deformity with similar outcomes as open approaches. While the endonasal endoscopic approach to the masseteric and buccal spaces is unconventional, encapsulated tumors in these regions can be delivered into the nasal cavity through the maxilla and PPF with the use of transoral finger-retraction. The authors present a case of a 10-year-old male referred to their tertiary care center with left-sided epistaxis, nasal obstruction, and facial swelling. Imaging demonstrated a vascular lesion in the PPF involving the left nasal cavity and paranasal sinuses, with extension into left middle cranial fossa, infratemporal fossa, orbit, and deep spaces of the neck including the masticator, masseteric, and buccal spaces. The patient underwent preoperative embolization and endoscopic endonasal surgical resection with transoral finger-retraction without complication. Transoral finger-retraction represents a supplemental technique that allows for encapsulated lesions involving the masseteric and buccal spaces to be delivered into the nasal cavity for endoscopic resection in a safe and effective fashion, preventing the need for transfacial incisions.

Extent of BOLD Vascular Dysregulation Is Greater in Diffuse Gliomas without Isocitrate Dehydrogenase 1 R132H Mutation.

Purpose To determine the effect that R132H mutation status of diffuse glioma has on extent of vascular dysregulation and extent of residual blood oxygen level-dependent (BOLD) abnormality after surgical resection. Materials and Methods This study was an institutional review board-approved retrospective analysis of an institutional database of patients, and informed consent was waived. From 2010 to 2017, 39 treatment-naïve patients with diffuse glioma underwent preoperative echo-planar imaging and BOLD functional magnetic resonance imaging. BOLD vascular dysregulation maps were made by identifying voxels with time series similar to tumor and dissimilar to healthy brain. The spatial overlap between tumor and vascular dysregulation was characterized by using the Dice coefficient, and areas of BOLD abnormality outside the tumor margins were quantified as BOLD-only fraction (BOF). Linear regression was used to assess effects of R132H status on the Dice coefficient, BOF, and residual BOLD abnormality after surgical resection. Results When compared with R132H wild-type (R132H-) gliomas, R132H-mutated (R132H+) gliomas showed greater spatial overlap between BOLD abnormality and tumor (mean Dice coefficient, 0.659 ± 0.02 [standard error] for R132H+ and 0.327 ± 0.04 for R132H-; P < .001), less BOLD abnormality beyond the tumor margin (mean BOF, 0.255 ± 0.03 for R132H+ and 0.728 ± 0.04 for R132H-; P < .001), and less postoperative BOLD abnormality (residual fraction, 0.046 ± 0.0047 for R132H+ and 0.397 ± 0.045 for R132H-; P < .001). Receiver operating characteristic curve analysis showed high sensitivity and specificity in the discrimination of R132H+ tumors from R132H- tumors with calculation of both Dice coefficient and BOF (area under the receiver operating characteristic curve, 0.967 and 0.977, respectively). Conclusion R132H mutation status is an important variable affecting the extent of tumor-associated vascular dysregulation and the residual vascular dysregulation after surgical resection. © RSNA, 2018 Online supplemental material is available for this article.

Direct, intraoperative observation of ~0.1 Hz hemodynamic oscillations in awake human cortex: implications for fMRI.

An almost sinusoidal, large amplitude ~0.1 Hz oscillation in cortical hemodynamics has been repeatedly observed in species ranging from mice to humans. However, the occurrence of 'slow sinusoidal hemodynamic oscillations' (SSHOs) in human functional magnetic resonance imaging (fMRI) studies is rarely noted or considered. As a result, little investigation into the cause of SSHOs has been undertaken, and their potential to confound fMRI analysis, as well as their possible value as a functional biomarker has been largely overlooked. Here, we report direct observation of large-amplitude, sinusoidal ~0.1 Hz hemodynamic oscillations in the cortex of an awake human undergoing surgical resection of a brain tumor. Intraoperative multispectral optical intrinsic signal imaging (MS-OISI) revealed that SSHOs were spatially localized to distinct regions of the cortex, exhibited wave-like propagation, and involved oscillations in the diameter of specific pial arterioles, indicating that the effect was not the result of systemic blood pressure oscillations. fMRI data collected from the same subject 4 days prior to surgery demonstrates that ~0.1 Hz oscillations in the BOLD signal can be detected around the same region. Intraoperative optical imaging data from a patient undergoing epilepsy surgery, in whom sinusoidal oscillations were not observed, is shown for comparison. This direct observation of the '0.1 Hz wave' in the awake human brain, using both intraoperative imaging and pre-operative fMRI, confirms that SSHOs occur in the human brain, and can be detected by fMRI. We discuss the possible physiological basis of this oscillation and its potential link to brain pathologies, highlighting its relevance to resting-state fMRI and its potential as a novel target for functional diagnosis and delineation of neurological disease.

Motor deficits correlate with resting state motor network connectivity in patients with brain tumours.

While a tumour in or abutting primary motor cortex leads to motor weakness, how tumours elsewhere in the frontal or parietal lobes affect functional connectivity in a weak patient is less clear. We hypothesized that diminished functional connectivity in a distributed network of motor centres would correlate with motor weakness in subjects with brain masses. Furthermore, we hypothesized that interhemispheric connections would be most vulnerable to subtle disruptions in functional connectivity. We used task-free functional magnetic resonance imaging connectivity to probe motor networks in control subjects and patients with brain tumours (n = 22). Using a control dataset, we developed a method for automated detection of key nodes in the motor network, including the primary motor cortex, supplementary motor area, premotor area and superior parietal lobule, based on the anatomic location of the hand-motor knob in the primary motor cortex. We then calculated functional connectivity between motor network nodes in control subjects, as well as patients with and without brain masses. We used this information to construct weighted, undirected graphs, which were then compared to variables of interest, including performance on a motor task, the grooved pegboard. Strong connectivity was observed within the identified motor networks between all nodes bilaterally, and especially between the primary motor cortex and supplementary motor area. Reduced connectivity was observed in subjects with motor weakness versus subjects with normal strength (P < 0.001). This difference was driven mostly by decreases in interhemispheric connectivity between the primary motor cortices (P < 0.05) and between the left primary motor cortex and the right premotor area (P < 0.05), as well as other premotor area connections. In the subjects without motor weakness, however, performance on the grooved pegboard did not relate to interhemispheric connectivity, but rather was inversely correlated with connectivity between the left premotor area and left supplementary motor area, for both the left and the right hands (P < 0.01). Finally, two subjects who experienced severe weakness following surgery for their brain tumours were followed longitudinally, and the subject who recovered showed reconstitution of her motor network at follow-up. The subject who was persistently weak did not reconstitute his motor network. Motor weakness in subjects with brain tumours that do not involve primary motor structures is associated with decreased connectivity within motor functional networks, particularly interhemispheric connections. Motor networks become weaker as the subjects become weaker, and may become strong again during motor recovery.

A 53-year-old woman with a rapidly progressive, non-enhancing left frontotemporal lesion.

Fifty-three-year-old woman presented with chronic, episodic headache.

Intranasal delivery of caspase-9 inhibitor reduces caspase-6-dependent axon/neuron loss and improves neurological function after stroke.

Despite extensive research to develop an effective neuroprotective strategy for the treatment of ischemic stroke, therapeutic options remain limited. Although caspase-dependent death is thought to play a prominent role in neuronal injury, direct evidence of active initiator caspases in stroke and the functional relevance of this activity have not previously been shown. Using an unbiased caspase-trapping technique in vivo, we isolated active caspase-9 from ischemic rat brain within 1 h of reperfusion. Pathogenic relevance of active caspase-9 was shown by intranasal delivery of a novel cell membrane-penetrating highly specific inhibitor for active caspase-9 at 4 h postreperfusion (hpr). Caspase-9 inhibition provided neurofunctional protection and established caspase-6 as its downstream target. The temporal and spatial pattern of expression demonstrates that neuronal caspase-9 activity induces caspase-6 activation, mediating axonal loss by 12 hpr followed by neuronal death within 24 hpr. Collectively, these results support selective inhibition of these specific caspases as an effective therapeutic strategy for stroke.

A Standardized Approach to Treatment Over Objection in Patients Lacking Decision-Making Capacity Secondary to Neurologic Disease.

Neurologic diseases, ranging from Alzheimer dementia to mass lesions in the frontal lobe, may impair decision making. When patients with neurologic disease lack decision-making capacity, but refuse treatment, should they be treated over their objection? To address this type of ethical dilemma in medical illness, Rubin and Prager developed a standardized 7-question approach: (1) How imminent is harm without intervention? (2) What is the likely severity of harm without intervention? (3) What are the risks of intervention? (4) What are the logistics of treating over objection? (5) What is the efficacy of the proposed intervention? (6) What is the likely emotional effect of a coerced intervention? (7) What is the patient's reason for refusal? We describe the application of the standardized Rubin/Prager approach as a checklist to the case of a 50-year-old woman with a large frontal lobe meningioma, who lacked capacity as a result of the meningioma, but refused surgery. This approach may be applied to similar ethical dilemmas of treatment over objection in patients lacking capacity as a result of neurologic disease.

Deconvolution of cell type-specific drug responses in human tumor tissue with single-cell RNA-seq.

BACKGROUND: Preclinical studies require models that recapitulate the cellular diversity of human tumors and provide insight into the drug sensitivities of specific cellular populations. The ideal platform would enable rapid screening of cell type-specific drug sensitivities directly in patient tumor tissue and reveal strategies to overcome intratumoral heterogeneity. METHODS: We combine multiplexed drug perturbation in acute slice culture from freshly resected tumors with single-cell RNA sequencing (scRNA-seq) to profile transcriptome-wide drug responses in individual patients. We applied this approach to drug perturbations on slices derived from six glioblastoma (GBM) resections to identify conserved drug responses and to one additional GBM resection to identify patient-specific responses. RESULTS: We used scRNA-seq to demonstrate that acute slice cultures recapitulate the cellular and molecular features of the originating tumor tissue and the feasibility of drug screening from an individual tumor. Detailed investigation of etoposide, a topoisomerase poison, and the histone deacetylase (HDAC) inhibitor panobinostat in acute slice cultures revealed cell type-specific responses across multiple patients. Etoposide has a conserved impact on proliferating tumor cells, while panobinostat treatment affects both tumor and non-tumor populations, including unexpected effects on the immune microenvironment. CONCLUSIONS: Acute slice cultures recapitulate the major cellular and molecular features of GBM at the single-cell level. In combination with scRNA-seq, this approach enables cell type-specific analysis of sensitivity to multiple drugs in individual tumors. We anticipate that this approach will facilitate pre-clinical studies that identify effective therapies for solid tumors.

Elevated troponin levels are predictive of mortality in surgical intracerebral hemorrhage patients.

OBJECTIVE: Elevated troponin levels are a common occurrence after ischemic stroke and subarachnoid hemorrhage (SAH), and have been described as a neurogenic form of myocardial injury. The prognostic significance of this event is controversial with numerous studies citing conflicting results. The importance of cardiac stress is of particular relevance in the operative management of intracerebral hemorrhage (ICH). To this end, we investigated whether troponin levels were an independent predictor of in-hospital mortality from all causes in surgically treated ICH patients. METHODS: We performed a retrospective analysis of 110 patients admitted to Columbia Presbyterian hospital between 1999 and 2007 for ICH and subsequent clot evacuation. Those with angina or recent myocardial infarction were excluded. CT scans were reviewed to determine hematoma size, location, presence of intraventricular hemorrhage (IVH) or SAH, hydrocephalus, and midline shift. Hospital records were examined for known demographic and clinical predictors of mortality. Univariate analysis was used to screen for predictive factors (P

Pediatric sinonasal and skull base lesions.

Pediatric skull base lesions are complex and challenging disorders. Safe and comprehensive management of this diverse group of disorders requires the expertise of an experienced multidisciplinary skull base team. Adult endoscopic skull base surgery has evolved due to technologic and surgical advancements, multidisciplinary team approaches, and continued innovation. Similar principles continue to advance the care delivered to the pediatric population. The approach and management of these lesions varies considerably based on tumor anatomy, pathology, and surgical goals. An understanding of the nuances of skull base reconstruction unique to the pediatric population is critical for successful outcomes.

Near real-time intraoperative brain tumor diagnosis using stimulated Raman histology and deep neural networks.

Intraoperative diagnosis is essential for providing safe and effective care during cancer surgery1. The existing workflow for intraoperative diagnosis based on hematoxylin and eosin staining of processed tissue is time, resource and labor intensive2,3. Moreover, interpretation of intraoperative histologic images is dependent on a contracting, unevenly distributed, pathology workforce4. In the present study, we report a parallel workflow that combines stimulated Raman histology (SRH)5-7, a label-free optical imaging method and deep convolutional neural networks (CNNs) to predict diagnosis at the bedside in near real-time in an automated fashion. Specifically, our CNNs, trained on over 2.5 million SRH images, predict brain tumor diagnosis in the operating room in under 150 s, an order of magnitude faster than conventional techniques (for example, 20-30 min)2. In a multicenter, prospective clinical trial (n = 278), we demonstrated that CNN-based diagnosis of SRH images was noninferior to pathologist-based interpretation of conventional histologic images (overall accuracy, 94.6% versus 93.9%). Our CNNs learned a hierarchy of recognizable histologic feature representations to classify the major histopathologic classes of brain tumors. In addition, we implemented a semantic segmentation method to identify tumor-infiltrated diagnostic regions within SRH images. These results demonstrate how intraoperative cancer diagnosis can be streamlined, creating a complementary pathway for tissue diagnosis that is independent of a traditional pathology laboratory.

Adjuvant embolization with N-butyl cyanoacrylate in the treatment of cerebral arteriovenous malformations: outcomes, complications, and predictors of neurologic deficits.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the frequency, severity, and predictors of neurological deficits after adjuvant embolization for cerebral arteriovenous malformations. METHODS: From 1997 to 2006, 202 of 275 patients with arteriovenous malformation received embolization before microsurgery (n=176) or radiosurgery (n=26). Patients were examined before and after endovascular embolization and at clinical follow-up (mean, 43.4+/-34.6 months). Outcome was classified according to the modified Rankin Scale. New neurological deficits after embolization were defined as minimal (no change in overall modified Rankin Scale), moderate (modified Rankin Scale < or =2), or significant (modified Rankin Scale >2). RESULTS: Two hundred two patients were treated in 377 embolization procedures. There were a total of 29 new clinical deficits after embolization (8% of procedures; 14% of patients), of which 19 were moderate or significant. Postembolization deficits resolved in a significant number of patients over time (P<0.0001). Five patients had persistent neurological deficits due to embolization (1.3% of procedures; 2.5% of patients). In multivariate analysis, the following variables significantly predicted new neurological deficit after embolization: complex arteriovenous malformation with treatment plan specifying more than one embolization procedure (OR, 2.7; 95% CI, 1.4 to 8.6), diameter <3 cm (OR, 3.2; 95% CI, 1.2 to 9.1), diameter >6 cm (OR, 6.2; 95% CI, 1.0 to 57.0), deep venous drainage (OR, 2.7; 95% CI, 1.1 to 6.9), or eloquent location (OR, 2.4; 95% CI, 1.0 to 5.7). These variables were weighted and used to compute an arteriovenous malformation Embolization Prognostic Risk Score for each patient. A score of 0 predicted no new deficits, a score of 1 predicted a new deficit rate of 6%, a score of 2 predicted a new deficit rate of 15%, a score of 3 predicted a new deficit rate of 21%, and a score of 4 predicted a new deficit rate of 50% (P<0.0001). CONCLUSIONS: Small and large size, eloquent location, deep venous drainage, and complex vascular anatomy requiring multiple embolization procedures are risk factors for the development of immediate postembolization neurological deficits. Nevertheless, a significant number of patients with treatment-related neurological deficits improve over time. The low incidence of permanent neurological deficits underscores the usefulness of this technique in carefully selected patients.

The complement cascade: new avenues in stroke therapy.

Recent evidence has shown that after the initial occlusion, a large portion of stroke patients achieve some degree of reperfusion either through collateral circulation or clot dissolution. However, it appears that this reperfusion may lead to increased inflammation-induced damage. Even though the exact mechanism of this secondary injury is unclear, several experimental studies have indicated an intimate connection between complement and this secondary form of damage. We review the available literature and attempt to identify promising clinical therapeutic targets.

Efficacy of lamina terminalis fenestration in reducing shunt-dependent hydrocephalus following aneurysmal subarachnoid hemorrhage: a systematic review. Clinical article.

OBJECT: Chronic hydrocephalus requiring shunt placement is a common complication following aneurysmal subarachnoid hemorrhage (SAH). Controversy exists over whether microsurgical fenestration of the lamina terminalis during aneurysm surgery affords a reduction in the development of shunt-dependent hydrocephalus. To resolve this debate, the authors performed a systematic review and quantitative analysis of the literature to determine the efficacy of lamina terminalis fenestration in reducing aneurysmal SAH-associated shunt-dependent hydrocephalus. METHODS: A MEDLINE (1950-2007) database search was performed using the following keywords, singly and in combination: "ventriculoperitoneal shunt," "hydrocephalus," "subarachnoid hemorrhage," "aneurysm," "fenestration," and "lamina terminalis." Additional studies were manually singled out by scrutinizing references from identified manuscripts, major neurosurgical journals and texts, and personal files. A recent study from the authors' institution was also incorporated into the review. Data from included studies were analyzed using the chi-square analysis and Student t-test. The Cochran-Mantel-Haenszel test was used to compare overall incidence of shunt-dependent hydrocephalus. RESULTS: The literature search revealed 19 studies, but only 11 were included in this review, involving 1973 patients. The fenestrated and nonfenestrated cohorts (combined from the various studies) differed significantly with regard to patient sex, age, and clinical grade as well as aneurysm location (p=0.0065, 0.0028, 0.0003, and 0.017, respectively). The overall incidence of shunt-dependent hydrocephalus in the fenestrated cohort was 10%, as compared with 14% in the nonfenestrated cohort (p=0.089). The relative risk of shunt-dependent hydrocephalus in the fenestrated cohort was 0.88 (95% CI 0.62-1.24). CONCLUSIONS: This systematic review revealed no significant association between lamina terminalis fenestration and a reduced incidence of shunt-dependent hydrocephalus. The interpretation of these results, however, is restricted by unmatched cohort differences as well as other inherent study limitations. Although the overall literature supports lamina terminalis fenestration, a number of authors have questioned the technique's benefits, thus rendering its efficacy in reducing shunt-dependent hydrocephalus unclear. A well-designed, multicenter, randomized controlled trial is needed to definitively address the efficacy of this microsurgical technique.

The role of indirect extracranial-intracranial bypass in the treatment of symptomatic intracranial atheroocclusive disease.

OBJECT: The optimal treatment of medically refractory intracranial atheroocclusive disease remains unclear. The EC-IC Bypass Study Investigators found that patients with internal carotid and middle cerebral artery (ICA and MCA) occlusion received no benefit from direct superficial temporal artery to MCA bypass, and that patients with ICA occlusion and MCA stenosis may have actually fared worse after surgery, perhaps in part due to flow reversal in critical perforator-bearing segments. Although the results of recent investigations have suggested that direct bypass may be beneficial in a subgroup of patients with hemodynamic failure secondary to unilateral ICA occlusion, similar data do not exist for patients with hemodynamic failure from other intracranial stenoocclusive diseases. Indirect bypass via encephaloduroarteriosynangiosis offers a surgical alternative that may avoid rapid flow reversal while providing additional flow to at-risk, distal vascular territories. METHODS: Twelve patients with medically resistant hemodynamic failure from intracranial atheroocclusive disease underwent indirect vascular bypass. Eight patients had ICA occlusion and coexistent MCA stenosis, 1 patient had tandem ICA stenoses and MCA stenosis, 1 patient had tandem ICA and MCA occlusion, 1 patient had ICA and posterior cerebral artery occlusion and an ischemic hemisphere supplied via a proximal superficial temporal artery branch, and 1 patient had poor donor arteries and severe medical comorbidities that precluded the use of general anesthesia. Patient evaluation included clinical assessment of neurological status, CT scanning, MR imaging, digital subtraction angiography, and transcranial Doppler ultrasonography with CO(2) reactivity, or SPECT with acetazolamide challenge. Patient records were reviewed and patients were interviewed for outcome assessment, including transient ischemic attack (TIA), cerebral infarction, change in cerebral perfusion, graft patency, and functional level according to the modified Rankin scale. Kaplan-Meier cumulative failure curves for the primary end point of cerebral infarction were used to compare these patients to a control group of 81 patients derived from the literature who received medical management for severe symptomatic hemodynamic failure. RESULTS: Eleven patients underwent encephaloduroarteriosynangiosis and 1 patient received bur holes with dural and arachnoid incisions; the mean length of follow-up was 51.2 +/- 40.1 months. Five patients had decreased perfusion on follow-up despite graft patency, and 10 patients suffered new infarctions or TIAs during the follow-up period. Five patients (42%) suffered infarctions within 1 year of surgery. A meta-analysis of 4 studies of patients with symptomatic ICA occlusion and severe hemodynamic failure who underwent medical treatment revealed a new infarction rate of 30% in the first year after entry into the study. There was no significant difference between patients with severe hemodynamic failure who underwent surgery and those in the medically treated control group (log-rank test, p = 0.179). CONCLUSIONS: The authors found that indirect bypass does not promote adequate pial collateral artery development and appears to be of limited utility in patients with symptomatic ICA or MCA stenoocclusive disease and secondary hemodynamic failure. Rates of postoperative TIAs or cerebral infarctions after indirect bypass in this patient population do not differ from previous reports in patients who received medical management only.

The role of polyamine metabolism in neuronal injury following cerebral ischemia.

Stroke is a leading cause of morbidity and mortality in the US, with secondary damage following the initial insult contributing significantly to overall poor outcome. Prior investigations have shown that the metabolism of certain polyamines such as spermine, spermidine, and putrescine are elevated in ischemic parenchyma, resulting in an increase in their metabolite concentration. Polyamine metabolites tend to be cytotoxic, leading to neuronal injury in the penumbra following stroke and expansion of the area of infarcted tissue. Although the precise mechanism is unclear, the presence of reactive aldehydes produced through polyamine metabolism, such as 3-aminopropanal and acrolein, have been shown to correlate with the incidence of cerebral vasospasm, disruption of oxidative metabolism and mitochondrial functioning, and disturbance of cellular calcium ion channels. Regulation of the polyamine metabolic pathway, therefore, may have the potential to limit injury following cerebral ischemia. To this end, we review this pathway in detail with an emphasis on clinical applicability.

Evaluation of a revised Glasgow Coma Score scale in predicting long-term outcome of poor grade aneurysmal subarachnoid hemorrhage patients.

Although many scales attempt to predict outcome following aneurysmal subarachnoid hemorrhage (aSAH), none have achieved universal acceptance, and most scales in common use are not statistically derived. We propose a statistically validated scale for poor grade aSAH patients that combines the Hunt and Hess grades and the Glasgow Coma Scale (GCS) scores; we refer to this as the Poor Grade GCS (PGS). The GCS scores of 160 poor grade aSAH patients (Hunt and Hess Grades 4 and 5) were recorded throughout their hospital stay. Outcomes were assessed by the modified Rankin scale (mRS). Analysis of variance and the Chi-square test were used to guide an analysis of GCS breakpoints according to outcomes. Multivariable logistic regression analysis was used to assess the ability of the Hunt and Hess, GCS, World Federation of Neurological Surgeons Grading Scale, and the PGS to predict long-term outcome. Outcome analysis revealed significant breakpoints in admission GCS scores: PGS-A (GCS 10-12); PGS-B (GCS 8-9); PGS-C (GCS 5-7); PGS-D (GCS 3-4) (p<0.001). In surgical patients, 95.2% of PGS-A, 58.1% of PGS-B, 35.4% of PGS-C, and 28.6% of PGS-D had a favorable one-year outcome. When controlling for age, sex, and operation status, PGS was the only scale predictive of long-term outcome. The odds ratios (OR) for unfavorable outcome according to PGS admission scores (with PGS-A as the reference) were: PGS-B, OR=14.2 (95% CI 1.5-140.5); PGS-C, OR=38.5 (95% CI 4.2-340.0); and PGS-D, OR=63.4 (95% CI 5.6-707.1). In addition to PGS admission scores, an age of 70 or greater was a significant predictor of poor outcome with an OR of 7.5 (95% CI 1.8-30.7). No patients with a PGS-C or PGS-D over the age of 70 had a favorable long-term outcome. Therefore, elements of the Hunt and Hess and GCS can be combined into the PGS to predict long-term outcome in poor grade aSAH patients. However, patients with PGS-C and PGS-D over the age of 70 should be assessed carefully prior to definitive treatment.

Predicting long-term outcome in poor grade aneurysmal subarachnoid haemorrhage patients utilising the Glasgow Coma Scale.

The Glasgow Coma Scale (GCS) is the most universally accepted system for grading level of consciousness. Predicting outcome is particularly difficult in poor grade aneurysmal subarachnoid haemorrhage (aSAH) patients. We hypothesised that the GCS and individual examination components would correlate with long-term outcome and have varying prognostic value depending on assessment time points. GCS scores of 160 aSAH patients presenting in stupor or coma were prospectively recorded on admission and each subsequent day until hospital day 14. Early treatment was planned for each patient unless the patient's family refused aggressive intervention or the patient died before surgery. Outcomes were assessed by the modified Rankin scale (mRS) at 14 days, 3 months, and one year. All patients who did not receive surgical treatment died within one year. Of the 104 patients who received surgical treatment, 13.5% of them had a favourable outcome at 14 days, 38.5% at 3 months, and 51% at one year (p<0.0001). Admission GCS scores significantly correlated with outcome (Spearman rank test, rs=0.472, p<0.0001). On admission, motor examination correlated best with one-year outcome (rs=0.533, p<0.0001). Each point increase in motor examination predicted a 1.8-fold increased odds of favourable long-term outcome (95% confidence interval [CI], 1.4-2.3). At discharge, eye examination (rs=0.760, p<0.0001) correlated best with one-year outcome, and a one point increase in eye examination predicted a 3.1-fold increased odds of favourable outcome (95% CI, 1.8-5.4). During hospitalisation, the best eye exam (rs=0.738, p<0.0001) and worst motor exam (rs=0.612, p<0.0001) were the most highly correlated with the one-year outcome. Long-term follow-up is necessary when evaluating recovery after aSAH, as outcomes improve significantly during the first year. The GCS and its individual components correlate well with long-term outcome. Admission motor examination and spontaneous eye opening during hospitalisation are most predictive of favourable recovery.

Neuronal RAGE expression modulates severity of injury following transient focal cerebral ischemia.

Inflammation has a significant role in the neurological injury that follows stroke. The receptor for advanced-glycation end products (RAGE) is a multiligand member of the immunoglobulin superfamily that has been implicated in multiple neuronal and inflammatory stress processes. To directly test the role of neuronal RAGE in stroke, we employed two cohorts of transgenic mice, one over-expressing full-length functional human RAGE in neurons, and the other a human RAGE transgene in which deletion of the cytoplasmic domain of the receptor in neurons suppresses signal transduction stimulated by ligands (referred to as dominant negative or DN-RAGE). We found a statistically significant increase in stroke volume in the RAGE over-expressing cohort compared to normal controls, and a trend towards decreased stroke volume in the DN RAGE cohort. These results indicate that RAGE signaling directly contributes to pathology in cerebral ischemia.