CT Perfusion Does Not Modify the Effect of Reperfusion in Patients with Acute Ischemic Stroke Undergoing Endovascular Treatment in the ESCAPE-NA1 Trial.

BACKGROUND AND PURPOSE: Although reperfusion is associated with improved outcomes in patients with acute ischemic stroke undergoing endovascular treatment, many patients still do poorly. We investigated whether CTP modifies the effect of near-complete reperfusion on clinical outcomes, ie, whether poor clinical outcomes despite near-complete reperfusion can be partly or fully explained by CTP findings. MATERIALS AND METHODS: Data are from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial. Admission CTP was processed using RAPID software, generating relative CBF and CBV volume maps at standard thresholds. CTP lesion volumes were compared in patients with-versus-without near-complete reperfusion. Associations between each CTP metric and clinical outcome (90-day mRS) were tested using multivariable logistic regression, adjusted for baseline imaging and clinical variables. Treatment-effect modification was assessed by introducing CTP lesion volume × reperfusion interaction terms in the models. RESULTS: CTP lesion volumes and reperfusion status were available in 410/1105 patients. CTP lesion volumes were overall larger in patients without near-complete reperfusion, albeit not always statistically significant. Increased CBF <34%, CBV <34%, CBV <38%, and CBV <42% lesion volumes were associated with worse clinical outcome (ordinal mRS) at 90 days. CTP core lesion volumes did not modify the treatment effect of near-complete recanalization on clinical outcome. CONCLUSIONS: CTP did not modify the effect of near-complete reperfusion on clinical outcomes. Thus, CTP cannot explain why some patients with near-complete reperfusion have poor clinical outcomes.

Strength of Association between Infarct Volume and Clinical Outcome Depends on the Magnitude of Infarct Size: Results from the ESCAPE-NA1 Trial.

BACKGROUND AND PURPOSE: Infarct volume is an important predictor of clinical outcome in acute stroke. We hypothesized that the association of infarct volume and clinical outcome changes with the magnitude of infarct size. MATERIALS AND METHODS: Data were derived from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, in which patients with acute stroke with large-vessel occlusion were randomized to endovascular treatment plus either nerinetide or a placebo. Infarct volume was manually segmented on 24-hour noncontrast CT or DWI. The relationship between infarct volume and good outcome, defined as mRS 0-2 at 90 days, was plotted. Patients were categorized on the basis of visual grouping at the curve shoulders of the infarct volume/outcome plot. The relationship between infarct volume and adjusted probability of good outcome was fitted with linear or polynomial functions as appropriate in each group. RESULTS: We included 1099 individuals in the study. Median infarct volume at 24 hours was 24.9 mL (interquartile range [IQR] = 6.6-92.2 mL). On the basis of the infarct volume/outcome plot, 4 infarct volume groups were defined (IQR = 0-15 mL, 15.1-70 mL, 70.1-200 mL, >200 mL). Proportions of good outcome in the 4 groups were 359/431 (83.3%), 219/337 (65.0%), 71/201 (35.3%), and 16/130 (12.3%), respectively. In small infarcts (IQR = 0-15 mL), no relationship with outcome was appreciated. In patients with intermediate infarct volume (IQR = 15-200 mL), there was progressive importance of volume as an outcome predictor. In infarcts of > 200 mL, outcomes were overall poor. CONCLUSIONS: The relationship between infarct volume and clinical outcome varies nonlinearly with the magnitude of infarct size. Infarct volume was linearly associated with decreased chances of achieving good outcome in patients with moderate-to-large infarcts, but not in those with small infarcts. In very large infarcts, a near-deterministic association with poor outcome was seen.

Comparison of 3 Different Types of Spinal Arteriovenous Shunts below the Conus in Clinical Presentation, Radiologic Findings, and Outcomes.

BACKGROUND AND PURPOSE: Spinal arteriovenous shunts below the conus constitute 3 types of lesions, which have previously been mainly described in case reports, given their rarity, and are sometimes misdiagnosed. The purpose of this study was to describe the features of each type and compare these types as to epidemiologic features, clinical and radiologic presentations, treatment, and outcomes in a consecutive series of 48 cases. MATERIALS AND METHODS: The prospectively collected data bases of 2 referral centers for spinal vascular lesions were retrospectively reviewed. Spinal arteriovenous shunts below the conus were defined as all dural and intradural shunts below the conus medullaris. Clinical features, radiologic findings, treatment results, and clinical outcomes were assessed. RESULTS: There were filum terminale arteriovenous fistulas in 11 patients (22.9%), radicular arteriovenous shunts in 7 patients (14.6%), and spinal dural arteriovenous fistulas in 30 patients (62.5%). Radicular arteriovenous shunts presented at a younger age (P = .017) and with a higher incidence of back pain symptoms (P = .037). A tethered spinal cord was found in 54.5% of patients with filum terminale arteriovenous fistulas and 23.3% of patients with spinal dural arteriovenous fistulas. After treatment, the angiographic complete obliteration rate was 89.4% and spinal function was improved significantly (P < .001). CONCLUSIONS: Three groups of spinal arteriovenous shunts below the conus can be differentiated according to clinical and radiologic features. Filum terminale arteriovenous fistulas are frequently associated with dysraphic malformations, which may suggest a particular embryologic origin.

The behaviour of residual tumour after the intentional incomplete excision of a vestibular schwannoma: is it such a bad thing to leave some behind?

OBJECTIVES: To evaluate the biological behaviour of tumour remnants intentionally left in the surgical bed following the incomplete excision of vestibular schwannomas (VS) and to review the relation between extent of resection and preservation of facial nerve function. METHODS: A retrospective chart review of 450 patients who underwent surgery for resection of VS over 23 years (1992-2014). Of these, 50 (11%) patients had residual tumour intentionally left on/around the facial nerve (near-total or subtotal excision) to preserve facial nerve function intra-operatively. The growth of residual tumour was evaluated using serial magnetic resonance imaging scanning; pre- and postoperative facial nerve function was assessed using the House-Brackmann grading scale. SETTING: Tertiary referral neurotology unit. RESULTS: Of the 42 non-NF2 cases where the tumour was intentionally incompletely excised, 28 (67%) patients underwent subtotal resection (mean follow-up 68.5 ± 39.0 months) and 14 (33%) underwent near-total resection (mean follow-up 72.9 ± 48.3 months). Three patients (all in subtotal resection group) showed regrowth. This was not statistically different from the near-total resection group (χ2 = 0.92, P = 0.31). The mean overall growth for these cases was 0.68 mm ± 0.32 mm/year. 5 (one near total, four subtotal) of the eight NF2 patients (62.5%) were excluded from our analysis. In the non-NF2 group, poor facial nerve outcomes (House-Brackmann scores of III-IV) were seen in 2/14 and V-VI in 3/14 of the near total compared with 7/25 and 4/25 respectively in the subtotal group. CONCLUSIONS: Given that the primary surgery for the VS was only for tumours that were relatively large or grew during conservative treatment, the low rate of tumour remnant growth (7%) is reassuring. It may be appropriate to have a lower threshold for leaving tumour on the facial nerve in non-NF2 patients where complete resection may jeopardise facial nerve function.

Sumatriptan improves postoperative quality of recovery and reduces postcraniotomy headache after cranial nerve decompression.

BACKGROUND: Microvascular decompression (MVD) is a surgical treatment for cranial nerve disorders via a small craniotomy. The postoperative pain of this procedure can be classified as surgical site somatic pain and postcraniotomy headache similar in nature to a migraine, including its association with photophobia, nausea, and vomiting. This headache can be difficult to treat and can impact on postoperative recovery. Sumatriptan is used to treat migraine-like headaches in various settings. This single-centre randomized controlled trial investigated whether postoperative administration of sumatriptan after MVD surgery impacts the quality of postoperative recovery. METHODS: Fifty patients who complained of postoperative headache after MVD were randomized to receive an s.c. injection of sumatriptan (6 mg) or saline. The primary outcome was quality of recovery as measured by the Quality of Recovery-40 (QoR-40) score at 24 h. RESULTS: The QoR-40 scores were significantly higher in the sumatriptan group (median 184; interquartile range 169-196) than in the placebo group (133; 119-155; P<0.01), suggesting higher quality of recovery. The sumatriptan group also had significantly lower headache scores at 4, 12, and 24 h. There were no significant differences in other secondary outcomes. CONCLUSIONS: Use of sumatriptan improved the quality of recovery as measured by the QoR-40 and reduction of headache at 24 h after surgery. Sumatriptan is a useful alternative treatment for postcraniotomy headache. The mechanism remains unknown but could be related to reduction in headache, mood modulation, or both, mediated by a serotonin effect. CLINICAL TRIAL REGISTRATION: NCT01632657.

Uncoupling Neogenin association with lipid rafts promotes neuronal survival and functional recovery after stroke.

The dependence receptor Neogenin and its ligand, the repulsive guidance molecule a (RGMa), regulate apoptosis and axonal growth in the developing and the adult central nervous system (CNS). Here, we show that this pathway has also a critical role in neuronal death following stroke, and that providing RGMa to neurons blocks Neogenin-induced death. Interestingly, the Neogenin pro-death function following ischemic insult depends on Neogenin association with lipid rafts. Thus, a peptide that prevents Neogenin association with lipid rafts increased neuronal survival in several in vitro stroke models. In rats, a pro-survival effect was also observed in a model of ocular ischemia, as well as after middle cerebral artery occlusion (MCAO). Treatments that prevented Neogenin association with lipid rafts improved neuronal survival and the complexity of the neuronal network following occlusion of the middle artery. Toward the development of a treatment for stroke, we developed a human anti-RGMa antibody that also prevents Neogenin association with lipid rafts. We show that this antibody also protected CNS tissue from ischemic damage and that its application resulted in a significant functional improvement even when administrated 6 h after artery occlusion. Thus, our results draw attention to the role of Neogenin and lipid rafts as potential targets following stroke.

Subcortical cystic lesions within the anterior superior temporal gyrus: a newly recognized characteristic location for dilated perivascular spaces.

SUMMARY: Cystic parenchymal lesions may pose an important diagnostic challenge, particularly when encountered in unexpected locations. Dilated perivascular spaces, which may mimic cystic neoplasms, are known to occur in the inferior basal ganglia and mesencephalothalamic regions; a focal preference within the subcortical white matter has not been reported. This series describes 15 cases of patients with cystic lesions within the subcortical white matter of the anterior superior temporal lobe, which followed a CSF signal; were located adjacent to a subarachnoid space; demonstrated variable surrounding signal change; and, in those that were followed up, showed stability. Pathology study results obtained in 1 patient demonstrated chronic gliosis surrounding innumerable dilated perivascular spaces. These findings suggest that dilated perivascular spaces may exhibit a regional preference for the subcortical white matter of the anterior superior temporal lobe. Other features-lack of clinical symptoms, proximity to the subarachnoid space, identification of an adjacent vessel, and stability with time-may help in confidently making the prospective diagnosis of a dilated perivascular space, thereby preventing unnecessary invasive management.

Mapping white matter diffusion and cerebrovascular reactivity in carotid occlusive disease.

OBJECTIVE: To characterize the relationship between cerebrovascular reactivity (CVR) and white matter (WM) diffusion in patients with internal carotid artery (ICA) occlusive disease. METHODS: In this exploratory observational study, 41 patients with severe stenosis or occlusion of the extracranial ICA and 12 healthy control subjects underwent CVR mapping using the fMRI response to hypercapnia. Conventional anatomic and diffusion-weighted MRI sequences were used to calculate maps of the apparent diffusion coefficient (ADC) and to exclude areas of previous ischemic injury. In all subjects, ADC was compared between WM with positive and negative CVR. In 27 patients with unilateral ICA involvement, ADC and CVR were compared between ipsilateral and contralateral WM while covarying for relevant clinical risk factors. RESULTS: In patients with bilateral disease and in the ipsilateral hemisphere of patients with unilateral disease, negative CVR was associated with increased WM ADC (p < 0.01 and p < 0.005, respectively). In patients with unilateral disease, the ipsilateral CVR deficit was correlated with the degree of hemispheric WM ADC elevation (p < 0.005). ADC elevation remained significant after correction for potential confounding risk factors. CONCLUSIONS: CVR impairment is associated with ADC elevation in normal-appearing WM of patients with severe stenosis or occlusion of the extracranial ICA. This finding is consistent with the presence of early, low-grade ischemic injury.

Quantitative measurement of cerebrovascular reactivity by blood oxygen level-dependent MR imaging in patients with intracranial stenosis: preoperative cerebrovascular reactivity predicts the effect of extracranial-intracranial bypass surgery.

BACKGROUND AND PURPOSE: CVR is a measure of cerebral hemodynamic impairment. A recently validated technique quantifies CVR by using a precise CO(2) vasodilatory stimulus and BOLD MR imaging. Our aim was to determine whether preoperative CO(2) BOLD CVR predicts the hemodynamic effect of ECIC bypass surgery in patients with intracranial steno-occlusive disease. MATERIALS AND METHODS: Twenty-five patients undergoing ECIC bypass surgery for treatment of intracranial stenosis or occlusion were recruited. CVR was measured preoperatively and postoperatively and expressed as %ΔBOLD MR signal intensity per mm Hg ΔPetCO(2). Using normative data from healthy subjects, we stratified patients on the basis of preoperative CVR into 3 groups: normal CVR, reduced CVR, and negative (paradoxical) CVR. Wilcoxon 2-sample tests (2-sided, α = 0.05) were used to determine whether the 3 groups differed with respect to change in CVR following bypass surgery. RESULTS: The group with normal preoperative CVR demonstrated no significant change in CVR following bypass surgery (mean, 0.22% ± 0.05% to 0.22% ± 0.01%; P = .881). The group with reduced preoperative CVR demonstrated a significant improvement following bypass surgery (mean, 0.08% ± 0.05% to 0.21 ± 0.08%; P < .001), and the group with paradoxical preoperative CVR demonstrated the greatest improvement (mean change, -0.04% ± 0.03% to 0.27% ± 0.03%; P = .028). CONCLUSIONS: Preoperative measurement of CVR by using CO(2) BOLD MR imaging predicts the hemodynamic effect of ECIC bypass in patients with intracranial steno-occlusive disease. The technique is potentially useful for selecting patients for surgical revascularization.

Impact of anatomical variations of the circle of Willis on the incidence of aneurysms and their recurrence rate following endovascular treatment.

AIM: To analyse the impact of anatomical variations of the parent arteries on the incidence and recurrence rate following coil embolization of aneurysms of the anterior (AcoA), posterior communicating artery (PcoA) and basilar artery (BA) tip. METHODS: Two hundred and two (96 AcoA, 67 PcoA, and 29 BA) aneurysms in 200 patients were treated with coil embolization between January 2000 and April 2008. Parent artery variations at each location were classified as: AcoA: A1 aplasia versus hypoplasia versus symmetrical size; PcoA: foetal origin versus medium versus small size, BA: cranial versus caudal versus asymmetrical fusion. The incidence of aneurysms and difference between recurrence rates for each group were recorded on follow-up. RESULTS: AcoA, PcoA, and BA aneurysms were more often associated with embryonically earlier vessel wall dispositions (A1 aplasia, foetal PcoA, asymmetrical fusion). Two of these variations were also associated with aneurysm recurrence following coil embolization: asymmetrical A1 segment (p=0.01), and asymmetrical BA tip (p=0.02). CONCLUSIONS: AcoA, PcoA, and BA tip aneurysms tend to occur more often in anatomically variant parent artery dispositions, some of which are related to aneurysm recurrence following coil embolization. This may relate to a more fragile vessel disposition as it is not fully matured or to altered haemodynamics secondary to the anatomical variations.

Quantification of cerebrovascular reactivity by blood oxygen level-dependent MR imaging and correlation with conventional angiography in patients with Moyamoya disease.

BACKGROUND AND PURPOSE: BOLD MR imaging combined with a technique for precision control of end-tidal pCO(2) was used to produce quantitative maps of CVR in patients with Moyamoya disease. The technique was validated against measures of disease severity by using conventional angiography; it then was used to study the relationship between CVR, vascular steal, and disease severity. MATERIALS AND METHODS: A retrospective analysis comparing conventional angiography with BOLD MR imaging was performed on 11 patients with Moyamoya disease. Iso-oxic cycling of end-tidal pCO(2) between 2 target values was performed during BOLD MR imaging. CVR was calculated as the BOLD signal difference per Delta pCO(2). CVR was correlated with the presence of Moyamoya or pial collaterals and the degree of Moyamoya disease as graded by using a modified Suzuki score. RESULTS: A good correlation between mean CVR and Suzuki score was found for the MCA and ACA territories (Pearson correlation coefficient, -0.7560 and -0.6140, respectively; P < .0001). A similar correlation was found between mean CVR and the presence of pial and Moyamoya collateral vessels for combined MCA and ACA territories (Pearson correlation coefficient, -0.7466; P < .0001). On a voxel-for-voxel basis, there was a greater extent of steal within vascular territories with increasing disease severity (higher modified Suzuki score). Mean CVR was found to scale nonlinearly with the extent of vascular steal. CONCLUSIONS: Quantitative measures of CVR show direct correlation with impaired vascular supply as measured by the modified Suzuki score and enable direct investigation of the physiology of autoregulatory reserve, including steal phenomenon, within a given vascular territory.

Management and clinical outcome of posterior fossa arteriovenous malformations: report on a single-centre 15-year experience.

OBJECTIVES: Posterior fossa brain arteriovenous malformations (PFbAVMs) are rare lesions. Management is complicated by eloquence of adjacent neurological structures, multimodality treatment is often necessary, and obliteration is not always possible. We describe a 15-year experience in the management of posterior fossa brain AVMs with a focus on clinical outcome. METHODS: From 1989 to 2004, prospectively collected information on 106 patients with diagnosis of a PFbAVMs was obtained. Clinical and angioarchitectural characteristics, management options and complications are described and reviewed to evaluate their impact on final outcome as measured by the Modified Rankin Score (mRS). RESULTS: Ninety-eight patients were followed for an average of 3.3 years (1-14.6). The male-to-female ratio was 1:1. Ninety-five out of 98 patients (96.9%) were symptomatic at presentation, with 61 (62.2%) intracranial haemorrhages. Sixty-two patients were treated (46 cerebellar, 16 brainstem). Ten haemorrhages occurred in follow-up (4.1%/year). The mRS was obtained in 62 patients and was classified as low (good, mRSor=3). Haemorrhage was the only predictor of poor mRS at presentation (p = 0.0229). A poor clinical outcome was correlated with the presence of AA (p = 0.0276), a poor initial mRS (p<0.0001) and the number of treatments needed (p = 0.0434). Patients were significantly more likely to improve than to deteriorate over time (p = 0.0201). CONCLUSION: The final clinical outcome in PFbAVMs relates directly with the presence of associated aneurysms, number of treatments needed to obliterate the AVM and mRS at presentation. Despite the fact that patients tend to improve after brain AVM haemorrhage, the relationship of MRS at presentation and final outcome suggests that an expedited, more definitive treatment is probably a better choice, especially in patients with good grades after the initial bleeding.

Postsynaptic mechanisms of excitotoxicity: Involvement of postsynaptic density proteins, radicals, and oxidant molecules.

Traditional models of neuronal excitotoxicity focused on the overactivation of receptors such as the ionotropic N-methyl-D-aspartate (NMDA)-subtype glutamate receptor. Recent developments have shifted focus to downstream neurotoxic signaling molecules with exciting implications to specific strategies for treating excitotoxic disorders. This review outlines these developments and introduces newly emerging evidence implicating the involvement of the melastatin subfamily in anoxic neuronal death. Both of these converge on the production of reactive oxygen species (ROS), including superoxide, nitric oxide (NO) and the oxidant peroxynitrite.

Anterior ethmoidal artery aneurysm and intracerebral hemorrhage.

The association between the formation of intracranial aneurysms and situations of increased blood flow in certain areas of the brain is well accepted today. It has been seen in association with arteriovenous malformations of the brain, carotid occlusion, and Moyamoya disease. The occurrence of aneurysms in small arteries of the skull base, with the exception of the intracavernous carotid artery, however, is rare. We report a case of a 55-year-old woman who presented with an intracerebral hemorrhage caused by a ruptured anterior ethmoidal artery aneurysm. To the best of our knowledge, this is only the second case of documented intracranial bleeding from such a lesion.

Multiple de novo vascular malformations in relation to diffuse venous occlusive disease: a case report.

Brain vascular malformations are dynamic disorders. Although mostly considered to be of congenital origin, the improvement of clinical imaging and vasculogenesis knowledge has shown that they might also result from a biological dysfunction of the remodeling process after birth. Venous occlusive disease and ishemia may represent powerful revealing triggers and support the capillary venous origin of some vascular malformations. We report a unique case of the development of multiple de novo vascular malformations (transverse sinus dural fistula and posterior fossa cavernomas) following acoustic neuroma surgery.

Molecular mechanisms of glutamate-dependent neurodegeneration in ischemia and traumatic brain injury.

Stroke and neurotrauma mediate neuronal death through a series of events that involve multiple interdependent molecular pathways. It has been suggested that these pathways are triggered following elevations in extracellular excitatory amino acids, primarily glutamate [1]. This report outlines mechanisms involving glutamate-mediated excitotoxicity with specific focus on (i) the role of Ca(2+) in neurotoxicity, (ii) The concept of 'source specificity' of neurotoxicity, (iii) the role of the ionotropic N-methyl-D-aspartate (NMDA)-subtype glutamate receptor and its associated submembrane molecules that may give rise to signaling specificity in excitotoxicity and (iv) the role of glutamate-mediated free-radical generation and associated cell death pathways. We also highlight a novel, peptide-based approach for uncoupling NMDA receptors from excitotoxicity in the rat central nervous system subjected to focal ischemia, thereby reducing stroke infarct volume and improving neurological functioning.

The influence of glutamate receptor 2 expression on excitotoxicity in Glur2 null mutant mice.

AMPA receptor (AMPAR)-mediated ionic currents that govern gene expression, synaptic strength, and plasticity also can trigger excitotoxicity. However, native AMPARs exhibit heterogeneous pharmacological, biochemical, and ionic permeability characteristics, which are governed partly by receptor subunit composition. Consequently, the mechanisms governing AMPAR-mediated excitotoxicity have been difficult to elucidate. The GluR2 subunit is of particular interest because it influences AMPAR pharmacology, Ca(2+) permeability, and AMPAR interactions with intracellular proteins. In this paper we used mutant mice lacking the AMPAR subunit GluR2 to study AMPAR-mediated excitotoxicity in cultured cortical neurons and in hippocampal neurons in vivo. We examined the hypothesis that in these mice the level of GluR2 expression governs the vulnerability of neurons to excitotoxicity and further examined the ionic mechanisms that are involved. In cortical neuronal cultures AMPAR-mediated neurotoxicity paralleled the magnitude of kainate-evoked AMPAR-mediated currents, which were increased in neurons lacking GluR2. Ca(2+) permeability, although elevated in GluR2-deficient neurons, did not correlate with excitotoxicity. However, toxicity was reduced by removal of extracellular Na(+), the main charge carrier of AMPAR-mediated currents. In vivo, the vulnerability of CA1 hippocampal neurons to stereotactic kainate injections and of CA3 neurons to intraperitoneal kainate administration was independent of GluR2 level. Neurons lacking the GluR2 subunit did not demonstrate compensatory changes in the distribution, expression, or function of AMPARs or of Ca(2+)-buffering proteins. Thus GluR2 level may influence excitotoxicity by effects additional to those on Ca(2+) permeability, such as effects on agonist potency, ionic currents, and synaptic reorganization.

Partial labyrinthectomy approach for brainstem vascular lesions.

Conventional wisdom has typically dictated that the bony labyrinth is an inviolate structure. This notion, however, was successfully challenged following the introduction of the partial labyrinthectomy approach, which was primarily used for the surgical management of cerebellopontine and petrous apex meningiomas. In this article, we discuss an extension of the technique of partial labyrinthectomy in a series of patients that has been used for the treatment of brainstem vascular lesions. We believe that this technique provides superior exposure to the brain stem when compared with conventional retrosigmoid and retrolabyrinthine approaches while reducing the inherent morbidity seen in transotic or petrosectomy approaches.

Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death.

Excitotoxicity is one of the most extensively studied processes of neuronal cell death, and plays an important role in many central nervous system (CNS) diseases, including CNS ischemia, trauma, and neurodegenerative disorders. First described by Olney, excitotoxicity was later characterized as an excessive synaptic release of glutamate, which in turn activates postsynaptic glutamate receptors. While almost every glutamate receptor subtype has been implicated in mediating excitotoxic cell death, it is generally accepted that the N-methyl-D-aspartate (NMDA) subtypes play a major role, mainly owing to their high calcium (Ca2+) permeability. However, other glutamate receptor subtypes such as 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionate (AMPA) or kainate receptors have also been attributed a critical role in mediating excitotoxic neuronal cell death. Although the molecular basis of glutamate toxicity is uncertain, there is general agreement that it is in large part Ca(2+)-dependent. The present review is aimed at summarizing the molecular mechanisms of NMDA receptor and AMPA/kainate receptor-mediated excitotoxic neuronal cell death.

Embolisation of Small (< 3 cm) Brain Arteriovenous Malformations. Correlation of Angiographic Results to a Proposed Angioarchitecture Grading System.

SUMMARY: The role of embolisation in the treatment of small < 3cm) brain arteriovenous malformations (AVMs) has not been elucidated. We reviewed our experience using embolisation in the treatment of small AVMs and correlated a proposed grading system based on the angioarchitecture to the percentage obliteration achieved by embolisation. Eighty-one small AVMs in 80 patients were embolised from 1984 to 1999. The age range was from 3 to 72 years. The AVMs were given a score from 0 to 6 based on the angioarchitecture. The assigned scores were as follows: nidus (fistula = 0, < 1 cm = 1, 1-3 cm = 2), type offeeding arteries (cortical = 0, perforator or choroidal = 1), number of feeding arteries (single = 0, multiple = 2) and number of draining veins (single = 0, multiple = 1). Angiographic results based on percentage obliteration were grouped into three categories: complete, 66-99%, and 0-65%. The goal of embolisation was cure in 27 AVMs, pre-surgical in 23, pre-radiosurgery in 26, and elimination of an aneurysm in five. Embolisation achieved complete obliteration in 22 (27%) of the 81 AVMs. In the AVMs where the goal was cure, 19 (70%) of 27 were completely obliterated. In the AVMs with angioarchitecture scores of 0-2, 12 (86%) of 14 were cured, with scores of 3-4, 8 (34%) of 24 were cured and with scores of 5-6, 2 (4%) of 44 were cured. Embolisation resulted in transient morbidity of 5.0%, permanent morbidity of 2.5%, and mortality of 1.2%. There were no complications in AVMs with scores of 0-2. Embolisation is an effective treatment of small AVMs when the angioarchitecture is favourable (scores 0-2). This includes pure fistulas and AVMs with a single, pial, feeding artery.