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

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

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.

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.

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.

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.

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.

Systemic expression of matrix metalloproteinase-9 in patients with cerebral arteriovenous malformations.

OBJECTIVE: Increased expression angiogenic factors, such as matrix metalloproteinases (MMPs), are associated with the formation of cerebral arteriovenous malformations (AVMs). The objective of this study was to determine plasma levels of MMP-9 of patients with AVMs. METHODS: Blood samples were drawn from 15 patients with AVMs before treatment, 24 hours postembolization, 24 hours postresection, and 30 days postresection. Blood samples were also obtained from 30 healthy controls. Plasma MMP-9 concentrations were measured via enzyme-linked immunosorbent assay. RESULTS: The mean plasma MMP-9 level in AVM patients at baseline was significantly higher than in control patients: 108.04 +/- 16.11 versus 41.44 +/- 2.44 ng/mL, respectively. The mean plasma MMP-9 level 1 day after embolization increased to 172.35 +/- 53.76 ng/mL, which was not significantly elevated over pretreatment levels. One day after resection, plasma MMP-9 levels increased significantly over pretreatment levels to 230.97 +/- 51.00 ng/mL. Mean plasma MMP-9 concentrations 30 days after resection decreased to 92.8 +/- 18.7 ng/mL, which was not different from pretreatment levels but was still significantly elevated over control levels. MMP-9 levels did not correlate with patient sex, age, presentation, or AVM size. CONCLUSION: Plasma MMP-9 levels are significantly elevated over controls at baseline, increase significantly immediately after surgery, and decrease to pretreatment levels during follow-up.

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

Clinical features, surgical treatment, and long-term outcome in adult patients with moyamoya disease. Clinical article.

OBJECT: The object of this study was to report the clinical features, surgical treatment, and long-term outcomes in adults with moyamoya phenomenon treated at a single institution in the US. METHODS: Forty-three adult patients with moyamoya disease (mean age 40 +/- 11 years [SD], range 18-69 years) were treated with encephaloduroarteriosynangiosis (EDAS). Neurologists examined patients pre- and postoperatively. Follow-up was obtained in person or by structured telephone interview (median 41 months, range 4-126 months). The following outcomes were collected: transient ischemic attack (TIA), infarction, graft collateralization, change in cerebral perfusion, and functional level according to the modified Rankin scale (mRS). Kaplan-Meier estimates of infarction risk were calculated for comparison of surgically treated and contralateral hemispheres. RESULTS: The majority of patients were women (65%), were Caucasian (65%), presented with ischemic symptoms (98%), and had bilateral disease (86%). Nineteen patients underwent unilateral and 24 patients bilateral EDAS (67 treated hemispheres). Collateral vessels developed in 50 (98%) of 52 hemispheres for which imaging was available and there was evidence of increased perfusion on SPECT scans in 41 (82%) of the 50 hemispheres evaluated. Periprocedural infarction (< 48 hours) occurred in 3% of the hemispheres treated. In the follow-up period patients experienced 10 TIAs, 6 infarctions, and 1 intracranial hemorrhage. Although the hemisphere selected for surgery was based upon patients' symptoms and severity of pathology, the 5-year infarction-free survival rate was 94% in the surgically treated hemispheres versus < 36% in the untreated hemispheres (p = 0.007). After controlling for age and sex, infarction was 89% less likely to occur in the surgically treated hemispheres than in the contralateral hemispheres (hazard ratio 0.11, 95% CI 0.02-0.56). Thirty-eight (88%) of 43 patients had preserved or improved mRS scores, relative to baseline status. CONCLUSIONS: In this mixed-race population of North American patients, indirect bypass promoted adequate pial collateral development and increased perfusion in the majority of adult patients with moyamoya disease. Patients had low rates of postoperative TIAs, infarction, and hemorrhage, and the majority of patients had preserved or improved functional status.

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 efficacy of direct extracranial-intracranial bypass in the treatment of symptomatic hemodynamic failure secondary to athero-occlusive disease: a systematic review.

OBJECTIVE: The 1985 International Extracranial-Intracranial (EC-IC) Bypass Trial failed to show a benefit following surgery in patients with varying degrees of angiographic ICA stenosis. More recent studies using modern technology to identify appropriate candidates, however, have generated promising findings. As a result, controversy exists regarding the role of this technique in the treatment of symptomatic athero-occlusive disease. To this end, we performed a systematic review and quantitative analysis of the literature to determine if a subset of patients with symptomatic hemodynamic failure secondary to athero-occlusive disease may benefit from direct EC-IC bypass. METHODS: We performed a MEDLINE (1985-2007) database search using the following keywords, singly and in combination: EC-IC bypass, hemodynamic failure and misery perfusion. Additional studies were identified manually by scrutinizing references from identified manuscripts, major neurosurgical journals and texts, and personal files. Our literature search divided studies into three categories: natural history of patients with stage I hemodynamic failure (16 studies, 2320 patients), natural history of patients with stage II hemodynamic failure (3 studies 163 patients), and outcomes of patients with hemodynamic failure treated by EC-IC bypass (23 studies 506 patients). RESULTS: Patients with severe stage I and stage II hemodynamic failure are at higher risk of cerebral infarction than those with mild disease (p=.014, OR 1.17-4.08 and p=0.10, OR 0.89-3.63, respectively). Additionally, patients with severe hemodynamic failure respond better to surgery than those with mild disease (p=0.03, OR 0.16-0.92). CONCLUSIONS: Patients with severe hemodynamic failure secondary to athero-occlusive disease appear to benefit from direct EC-IC bypass surgery. As a result, the conclusions of the 1985 International EC-IC Bypass Trial may not be applicable to this subset of patients. A randomized clinical trial involving this patient population is warranted.

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.

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.

Radiographic and clinical predictors of hemodynamic insufficiency in patients with athero-occlusive disease.

INTRODUCTION: Recent studies have shown that patients with increased oxygen extraction fraction (OEF) as measured by positron emission tomography (PET) have a substantially increased risk of stroke as a result of hemodynamic insufficiency. These patients appear to be ideal candidates for extracranial (EC)-intracranial (IC) bypass. The feasibility of this screening protocol, however, is controversial given PET's limited availability and high expense. A better understanding of the clinical factors that identify patients with potential hemodynamic insufficiency would streamline screening and improve cost-efficiency. METHODS: We performed a MEDLINE (1985-2007) database search for studies identifying clinical and radiographic predictors of hemodynamic failure and increased OEF on PET. We used the following key words, singly and in combination: "EC-IC bypass," "hemodynamic failure," and "misery perfusion." Additional studies were identified manually by scrutinizing references from manuscripts, major neurosurgical journals and texts, and personal files. Each study was reviewed for methodology, clinical criteria, and correlation with subsequent PET findings and stroke rates. A consensus was determined regarding the predictive value of each marker. RESULTS: Our literature search revealed 5 clinical and radiographic markers that have been used to identify patients with hemodynamic failure: orthostatic limb shaking, blurry vision on exposure to heat, leptomeningeal and ophthalmic collateral circulation on angiography, watershed infarction, and impaired vasodilatory response to acetazolamide. Orthostatic limb shaking is a rare finding but is predictive of hemodynamic failure and is associated with increased stroke risk. Blurry vision on exposure to heat is not predictive of increased stroke risk. Leptomeningeal and ophthalmic collateral circulation is a sensitive but not specific marker. Watershed infarction is highly sensitive and impaired vasodilatory response to acetazolamide is associated with increased OEF but may not be interchangeable. CONCLUSIONS: Orthostatic limb shaking, watershed infarction, collateral circulation, and impaired vasoreactivity to acetazolamide in patients with athero-occlusive disease may predict hemodynamic failure, increased OEF on PET, and high stroke rates. Recognition of these predictive markers may improve patient selection for surgical intervention, as such individuals appear to benefit from EC-IC bypass.