Incidence of clinically relevant psychiatric symptoms during glioblastoma treatment: an exploratory study.

PURPOSE: In addition to neurological symptoms glioblastoma (GBM) patients can experience psychiatric complaints, which are often hard to recognize and difficult to treat. Research on psychiatric symptoms during glioblastoma treatment is limited, but can have significant impact on quality of life, treatment processes and even survival. The aim of this study is to explore the incidence of clinically relevant psychiatric symptoms, during glioblastoma treatment and active surveillance. METHODS: Medical records of 302 GBM patients were reviewed from diagnostic surgery until discontinuation of treatment or active surveillance. Clinical relevance was defined as psychiatric symptoms that interfered with the oncological treatment and required referral to a psychiatrist. "Referred" versus "non-referred" GBM patients were compared using the Pearson Chi-Square test, Fisher's Exact Test or Mann Whitney-U test. RESULTS: Psychiatric symptoms occurred in 11.5% of patients during glioblastoma treatment or active surveillance, most often mood or behavioral symptoms, followed by psychotic symptoms. Referral occurred mainly during concomitant chemoradiation or adjuvant chemotherapy (64.3%). In 28.6% of patients psychiatric symptoms were thought to be attributive to medication. Treatment was discontinued in 17.9% of patients and temporarily interrupted in 3.6%. Possible risk factors included male gender, history of psychiatric disorder, postoperative delirium, non-frontal tumor location, anti-epileptic drug use at baseline and corticosteroid initiation during treatment. CONCLUSION: The found incidence of 11.5% and the high number of patients discontinuing treatment due to psychiatric symptoms justify more research in this, to date, understudied topic in scientific literature. Further prospective studies are needed to identify risk factors and unravel possible effects on survival.

Long-term feasibility of the new sutureless excimer laser-assisted non-occlusive anastomosis clip in a pig model.

BACKGROUND: High flow bypass surgery can be a last resort procedure for patients suffering from complex neurovascular pathology. Temporary occlusion of a recipient artery in these patients could result in debilitating neurological deficits. We developed a sutureless, mechanical anastomotic connection device, the SELANA clip (Sutureless Excimer Laser-Assisted Non-occlusive Anastomosis clip: SEcl). In the present study, we aim to determine the long-term non-inferiority of the SEcl technique compared with historical data of the conventional ELANA anastomosis technique. METHODS: A total of 18 SEcl bypasses were created on the carotid artery in a porcine model in 6 different survival groups. Mean application times, flap retrieval rates, hemostasis, patency, flow, endothelialization, and remodeling were assessed. RESULTS: The mean application time of the SEcl anastomoses was 15.2 ± 9.6 min, which was faster compared with the conventional ELANA anastomoses. The flap retrieval rate of the SEcl anastomoses was 86% (32/37). Direct hemostasis was achieved in 89% (33/37) SEcl anastomoses. Patency in all surviving animals was 94% (17/18). Bypass flow after six months was 156.5 ± 24.7 mL/min. Full endothelialization of the SEcl pins was observed after 3 weeks. CONCLUSION: The SEcl technique is not inferior to the ELANA technique regarding patency, flap retrieval rate, flow, and endothelialization. On the basis of a significantly shorter application time and superior hemostasis, the SEcl technique could be preferable over the ELANA technique. A pilot study in patients is a logical next step based on our current results.

Holographic patient tracking after bed movement for augmented reality neuronavigation using a head-mounted display.

BACKGROUND: Holographic neuronavigation has several potential advantages compared to conventional neuronavigation systems. We present the first report of a holographic neuronavigation system with patient-to-image registration and patient tracking with a reference array using an augmented reality head-mounted display (AR-HMD). METHODS: Three patients undergoing an intracranial neurosurgical procedure were included in this pilot study. The relevant anatomy was first segmented in 3D and then uploaded as holographic scene in our custom neuronavigation software. Registration was performed using point-based matching using anatomical landmarks. We measured the fiducial registration error (FRE) as the outcome measure for registration accuracy. A custom-made reference array with QR codes was integrated in the neurosurgical setup and used for patient tracking after bed movement. RESULTS: Six registrations were performed with a mean FRE of 8.5 mm. Patient tracking was achieved with no visual difference between the registration before and after movement. CONCLUSIONS: This first report shows a proof of principle of intraoperative patient tracking using a standalone holographic neuronavigation system. The navigation accuracy should be further optimized to be clinically applicable. However, it is likely that this technology will be incorporated in future neurosurgical workflows because the system improves spatial anatomical understanding for the surgeon.

Feasibility of the new sutureless excimer laser-assisted non-occlusive anastomosis clip in a rabbit model.

BACKGROUND: The excimer laser-assisted non-occlusive anastomosis (ELANA) technique facilitates the construction of anastomoses without temporary occlusion of the recipient artery. Experiments aimed at simplifying the technique eventually resulted in a sutureless ELANA slide (SEsl) anastomosis. After the first clinical use, new insights lead to the application of a clip at the back of the device, the SELANA clip (SEcl). The SEcl offers a distinct advantage over the SEsl since no sealant is necessary. In this study, we determine the feasibility of the SEcl anastomosis in an in vivo rabbit model. METHODS: 15 SEcl anastomoses and 15 conventional ELANA anastomoses were created on the abdominal aorta in 5 rabbits. Mean application times, flap retrieval rates, hemostasis, and burst pressures were assessed. RESULTS: The mean application time of the SEcl anastomoses was 11.4 min versus 39.0 min for the ELANA anastomoses (mean difference, 27.6 min; 95% CI, 20.6-34.7). The flap retrieval rate of the SEcl anastomoses (14/15) was not inferior to the flap retrieval rate of the ELANA anastomoses (13/15). Direct hemostasis was achieved in 13/15 (87%) SEcl anastomoses and in 14/15 (94%) ELANA anastomoses. All SEcl anastomoses were resistant to provoked pressures until 250 mmHg. CONCLUSION: The SEcl anastomosis is technically feasible in in vivo experiments. Mean application time, flap retrieval rate, hemostasis, and burst pressure are not inferior to the conventional ELANA anastomosis. Further long term experiments should be performed to assess safety, patency, and reendothelialization.

Bevacizumab may improve quality of life, but not overall survival in glioblastoma: an epidemiological study.

Background: The vascular endothelial growth factor antibody bevacizumab (Avastin®), received approval for the treatment of recurrent glioblastoma in many countries including the USA and Switzerland, but not the European Union, in 2009. Here, we explored the hypothesis that the approval of bevacizumab improved outcome with glioblastoma on a population level. Patients and methods: The prognostic significance of epidemiological, molecular genetic, and clinical data including treatment for glioblastoma patients diagnosed from 2010 to 2014 in the Canton of Zurich, Switzerland, was retrospectively analyzed using log-rank test and Cox proportional hazards models. Data were compared with data for the years 2005-2009. Results: In total, 310 glioblastoma patients were identified in the years 2010-2014. Median overall survival was 13.5 months for patients with known isocitrate dehydrogenase (IDH) wild-type (wt) (IDH1R132H-non-mutant) tumors (N = 248), compared with 11.3 months for IDH wt patients (P = 0.761) before (2005-2009). In the IDH wt cohort, bevacizumab use at any time increased from 19% in 2005-2009 to 49% in 2010-2014. Multivariate analysis did not identify bevacizumab exposure at any time to be associated with survival. Yet, upon the second-line treatment, baseline doses of corticosteroids were reduced by more than half in 83% of patients on bevacizumab compared with 48% of the patients treated with bevacizumab-free regimens (P = 0.007). Conclusion: This epidemiological study of a small, but clinically well-annotated patient cohort fails to support the assumption that the strong increase of bevacizumab use since 2010 improved survival in glioblastoma although clinical benefit associated with decreased steroid use may have been achieved.

Effect of Intraoperative Mixed-Reality use on Nonsurgical Team Members in the Neurosurgical Operating Room: An Explorative Study.

OBJECTIVES: Mixed-reality (MxR) implementation in the neurosurgical operating room (OR) is emerging, but the impact of this technology on the nonsurgical OR staff has not been investigated yet. The purpose of this study is to evaluate the nonsurgical OR team's perception of the impact of intraoperative MxR use. METHODS: The evaluation occurred in a neurosurgical institution implementing MxR perioperatively on a daily basis for 15 months. The questionnaire measuring the impact of MxR consisted of 5 binary questions and 4 subquestions measured on a 7-point Likert scale. RESULTS: Fifteen nonsurgical staff members of a neurosurgical OR team were interviewed. Most (85%) of the cohort stated that MxR changed their perception of the surgery, improving understanding of the spatial orientation (median 6, interquartile range 5-7) and of the pathology dimensions (6, 5.5-7). One participant (7%) was of the opinion that MxR disrupted the OR workflow. The majority (60%) stated that use of the holograms improved efficiency in the OR. The participants were neutral about the potential role of MxR to improve communication among different OR team members (4, 2-5) and overall teamwork (4, 2-5). CONCLUSIONS: The use of 3-Dimensional interactive holograms of neurosurgical cases in the nonsterile intraoperative phase was not perceived as distractive, and neither was OR flow disruption by members of the nonsurgical OR staff. MxR was considered an adjunct to improve OR efficiency. A thorough understanding of the impact of MxR's implementation on the nonsurgical staff could lead to targeted improvement of the MxR use and, potentially, to increasing the quality of the teamwork.

Effects of the introduction of the WHO "Surgical Safety Checklist" on in-hospital mortality: a cohort study.

OBJECTIVE: To evaluate the effect of implementation of the WHO's Surgical Safety Checklist on mortality and to determine to what extent the potential effect was related to checklist compliance. BACKGROUND: Marked reductions in postoperative complications after implementation of a surgical checklist have been reported. As compliance to the checklists was reported to be incomplete, it remains unclear whether the benefits obtained were through actual completion of a checklist or from an increase in overall awareness of patient safety issues. METHODS: This retrospective cohort study included 25,513 adult patients undergoing non-day case surgery in a tertiary university hospital. Hospital administrative data and electronic patient records were used to obtain data. In-hospital mortality within 30 days after surgery was the main outcome and effect estimates were adjusted for patient characteristics, surgical specialty and comorbidity. RESULTS: After checklist implementation, crude mortality decreased from 3.13% to 2.85% (P = 0.19). After adjustment for baseline differences, mortality was significantly decreased after checklist implementation (odds ratio [OR] 0.85; 95% CI, 0.73-0.98). This effect was strongly related to checklist compliance: the OR for the association between full checklist completion and outcome was 0.44 (95% CI, 0.28-0.70), compared to 1.09 (95% CI, 0.78-1.52) and 1.16 (95% CI, 0.86-1.56) for partial or noncompliance, respectively. CONCLUSIONS: Implementation of the WHO Surgical Checklist reduced in-hospital 30-day mortality. Although the impact on outcome was smaller than previously reported, the effect depended crucially upon checklist compliance.

Towards sutureless non-occlusive cerebral revascularization.

Sutureless vascular anastomoses have been the subject of extensive research for decades. In neurosurgery the need for a safe and fast technique is high, because temporary occlusion of cerebral arteries may rapidly lead to brain ischemia. Conventional sutured anastomoses have always been the golden standard. Limited working space and difficult suturing techniques were reasons to find alternatives. Many artificial devices to create anastomoses have been engineered over the years like tissue sealants, clips and automated suturing sets with variable success. For all previous options, temporary occlusion of the recipient artery was necessary. The Excimer Laser Assisted Non-Occlusive Anastomosis (ELANA) technique™ facilitates the construction of an end-to-side anastomosis without temporary occlusion of the recipient artery using a platinum ring and a laser. However, the technical challenge of intracranial micro-sutures remained. Experiments using less sutures eventually resulted in a sutureless ELANA (SELANA) anastomosis. After in vitro and in vivo experiments, the SELANA slide was considered feasible for intracranial use although some concrete improvements, like the inclusion of a clip at the back of the device, were needed. Therefore, the development of an ideal sutureless anastomosis is still ongoing. This process is an evolution rather than a revolution.

Investigating the Association of Wallerian Degeneration and Diaschisis After Ischemic Stroke With BOLD Cerebrovascular Reactivity.

INTRODUCTION: Wallerian degeneration and diaschisis are considered separate remote entities following ischemic stroke. They may, however, share common neurophysiological denominators, since they are both related to disruption of fiber tracts and brain atrophy over time. Therefore, with advanced multimodal neuroimaging, we investigate Wallerian degeneration and its association with diaschisis. METHODS: In order to determine different characteristics of Wallerian degeneration, we conducted examinations on seventeen patients with chronic unilateral ischemic stroke and persisting large vessel occlusion, conducting high-resolution anatomical magnetic resonance imaging (MRI) and blood oxygenation-level dependent cerebrovascular reactivity (BOLD-CVR) tests, as well as Diamox 15(O)-H2O-PET hemodynamic examinations. Wallerian degeneration was determined using a cerebral peduncle asymmetry index (% difference of volume of ipsilateral and contralateral cerebral peduncle) of more than two standard deviations away from the average of age-matched, healthy subjects (Here a cerebral peduncle asymmetry index > 11%). Diaschisis was derived from BOLD-CVR to assess the presence of ipsilateral thalamus diaschisis and/or crossed cerebellar diaschisis. RESULTS: Wallerian degeneration, found in 8 (47%) subjects, had a strong association with ipsilateral thalamic volume reduction (r 2 = 0.60) and corticospinal-tract involvement of stroke (p < 0.001). It was also associated with ipsilateral thalamic diaschisis (p = 0.021), No cerebral peduncular hemodynamic differences were found in patients with Wallerian degeneration. In particular, no CBF decrease or BOLD-CVR impairment was found. CONCLUSION: We show a strong association between Wallerian degeneration and ipsilateral thalamic diaschisis, indicating a structural pathophysiological relationship.

Induction of brain aquaporin 9 (AQP9) in catecholaminergic neurons in diabetic rats.

Aquaporin 9 facilitates the diffusion of water but also glycerol and monocarboxylates, known as brain energy substrates. AQP9 was recently observed in catecholaminergic neurons that are implicated in energy homeostasis and also possibly in neuroendocrine effects of diabetes. Recently it has been observed that the level of AQP9 expression in hepatocytes is sensitive to the blood concentration of insulin. Furthermore, insulin injection in the brain is known to be related to the energy homeostasis. Based on these observations, we investigated if the concentration of insulin affects the level of brain AQP9 expression and if so, in which cell types. This study has been carried out, in a model of the diabetic rat generated by streptozotocin injection and on brainstem slices. In diabetic rats showing a decrease in systemic insulin concentration, AQP9 is only increased in brain areas containing catecholaminergic neurons. In contrast, no significant change is detected in the cerebral cortex and the cerebellum. Using immunocytochemistry, we are able to show that the increase in AQP9 expression is specifically present in catecholaminergic neurons. In brainstem slice cultures, 2 microM insulin induces a significant decrease in AQP9 protein levels 6 h after application, suggesting that brain AQP9 is also regulated by the insulin. These results show that the level of expression of brain AQP9 is affected by variations of the concentration of insulin in a diabetic model and in vitro.

Quantification of Intracranial Aneurysm Volume Pulsation with 7T MRI.

BACKGROUND AND PURPOSE: Aneurysm volume pulsation is a potential predictor of intracranial aneurysm rupture. We evaluated whether 7T MR imaging can quantify aneurysm volume pulsation. MATERIALS AND METHODS: In Stage I of the study, 10 unruptured aneurysms in 9 patients were studied using a high-resolution (0.6-mm, isotropic) 3D gradient-echo sequence with cardiac gating. Semiautomatic segmentation was used to measure aneurysm volume (in cubic millimeters) per cardiac phase. Aneurysm pulsation was defined as the relative increase in volume between the phase with the smallest volume and the phase with the largest volume. The accuracy and precision of the measured volume pulsations were addressed by digital phantom simulations and a repeat image analysis. In Stage II, the imaging protocol was optimized and 9 patients with 9 aneurysms were studied with and without administration of a contrast agent. RESULTS: The mean aneurysm pulsation in Stage I was 8% ± 7% (range, 2%-27%), with a mean volume change of 15 ± 14 mm3 (range, 3-51 mm3). The mean difference in volume change for the repeat image analysis was 2 ± 6 mm3. The artifactual volume pulsations measured with the digital phantom simulations were of the same magnitude as the volume pulsations observed in the patient data, even after protocol optimization in Stage II. CONCLUSIONS: Volume pulsation quantification with the current imaging protocol on 7T MR imaging is not accurate due to multiple imaging artifacts. Future studies should always include aneurysm-specific accuracy analysis.

CT angiography and perfusion CT in cerebral vasospasm after subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: We investigated the association of multisection CT angiography (MSCTA) and perfusion CT (PCT) for the characterization of vasospasm secondary to aneurysmal subarachnoid hemorrhage. MATERIALS AND METHODS: Among 27 patients with symptomatic cerebrovascular vasospasm investigated by digital subtraction angiography (DSA), 18 underwent both cerebral PCT and MSCTA. For the remaining 9, only PCT or MSCTA could be performed. MSCTA was compared with DSA for the detection and characterization of vasospasm on 286 intracranial arterial segments. PCT maps were visually reviewed for mean transit time, relative cerebral blood flow, and relative cerebral blood volume abnormalities and were qualitatively compared with the corresponding regional vasospasm detected by DSA. RESULTS: Vasospasm was grouped into 2 categories: mild-moderate and severe. The depiction of vasospasm by MSCTA showed the best sensitivity, specificity, and accuracy at the level of the A2 and M2 arterial segments (100% for each), in contrast to the carotid siphon (45%, 100%, and 85% respectively). The characterization of vasospasm severity by MSCTA showed a sensitivity, specificity, and accuracy of 86.8%, 96.8%, and 95.2%, respectively, for mild-moderate vasospasm, and 76.5%, 99.5%, and 97.5%, respectively, for severe vasospasm. The PCT abnormalities were related to severe vasospasm in 9 patients and to mild-to-moderate vasospasm in 2. The sensitivity, specificity, and accuracy of PCT in detecting vasospasm were 90%, 100%, and 92.3%, respectively, for severe vasospasm, and 20%, 100%, and 38.5%, respectively, for mild-moderate vasospasm. CONCLUSION: MSCTA/PCT can assess the location and severity of cerebrovascular vasospasm and its related perfusion abnormalities. It can identify severe vasospasm with risk of delayed ischemia and can thus guide the invasive treatment.

Cerebral vascular autoregulation assessed by perfusion-CT in severe head trauma patients.

PURPOSE: To use perfusion-CT technique in order to characterize cerebral vascular autoregulation in a population of severe head trauma patients with features of cerebral edema either on the admission or on the follow-up conventional noncontrast cerebral CT. MATERIAL AND METHODS: A total of 80 perfusion-CT examinations were obtained in 42 severe head trauma patients with features of cerebral edema on conventional noncontrast cerebral CT, either on admission or during follow-up. Perfusion-CT results, i.e. the regional cerebral blood volume (rCBV) and flow (rCBF), were correlated with the mean arterial pressure (MAP) measured during each perfusion-CT examination. Ratios were defined to integrate the concept of cerebral vascular autoregulation, and cluster analysis performed, which allowed identification of different subgroups of patients. MAP values and perfusion-CT results in these groups were compared using Kruskal-Wallis and Wilcoxon (Mann-Whitney) tests. Moreover, the functional outcome of the 42 patients was evaluated 3 months after trauma on the basis of the Glasgow Outcome Scale (GOS) score and similarly compared between groups. RESULTS: Three main groups of patients were identified: 1) 22 perfusion-CT examinations were collected in 13 patients, characterized by high rCBV and rCBF values and by significant dependence of perfusion-CT rCBV and rCBF results on MAP values (p<0.001), 2) 23 perfusion-CT examinations collected in 19 patients showing perfusion-CT results similar to control trauma subjects, and 3) 33 perfusion-CT collected in 16 patients, with low rCBV and rCBF values and near-independence of perfusion-CT results with respect to MAP values. The first group was interpreted as showing impaired cerebral vascular autoregulation, which was preserved in the third group. The second group was associated with the best functional outcome; it was linked to the first group, because eight patients went from one group to the other from admission to follow-up. CONCLUSION: Perfusion-CT in severe head trauma patients was able to provide direct and quantitative assessment of cerebral vascular autoregulation with a single measurement. It could hence be used as a guide for brain edema therapy, as well as to monitor the treatment efficiency.

Giant and complex aneurysms treatment with preservation of flow via bypass technique.

Due to their anatomical characteristics and the complexity of the procedures required to obtain their complete occlusion, the treatment of giant intracranial aneurysms is a real challenge. Direct reconstructive strategies, whether by interventional neuroradiology (coils, stents) or microsurgical (clipping) means, are not always applicable and, in patients that would not tolerate parent or collateral artery sacrifice, the adjunction of a revascularization procedure using a bypass technique might be necessary. Cerebral arterial bypasses can be classified according to their function (3 types: flow replacement, flow reversal or protective), the branching mode of the graft used (3 types: pedicled, interpositional or in situ), the sites of anastomosis (2 types: extracranial-intracranial or intracranial-intracranial) and the class of flow they are supposed to provide (3 types: low-, intermediate- or high-flow). In this article, the authors review the different aspects in the management of patients with a giant intracranial aneurysm using a bypass: preoperative work-up, types of bypass and indications, surgical techniques and results.

Brain biopsy in patients with acquired immunodeficiency syndrome: diagnostic value, clinical performance, and survival time.

BACKGROUND: Despite extensive discussion in recent years, brain biopsy in patients positive for human immunodeficiency virus who manifest cerebral mass lesions remains an ill-defined step in management. METHODS: Prebiopsy data of 26 human immunodeficiency virus-positive patients with cerebral mass lesions who underwent computed tomography-guided stereotactic brain biopsy (SBB) were reviewed by a specialist in infectious diseases and by a neuroradiologist to establish a clinical diagnosis and a treatment plan for each patient. The postbiopsy diagnosis was compared with the prebiopsy diagnosis. Long-term patient outcome after SBB was recorded by means of a clinical performance scale to estimate its impact on life expectancy and clinical performance. RESULTS: The SBB was diagnostic in 25 patients (96%). Potentially treatable disease was diagnosed in 21 patients (81%), and specific therapy was initiated in 17 patients (65%); 10 patients (39%) were able to complete therapy. The SBB corroborated the clinical diagnosis in 13 (52%) of 25 patients. The group with identical clinical and biopsy-proved diagnoses showed significantly better response to therapy (P = .02), clinical performance (P = .04), and survival after biopsy (P = .01), as compared with the group with different clinical and biopsy-proved diagnosis, although no significant difference was found for the degree of immunosuppression. Only completion of the treatment plan increased life expectancy significantly (P = .008). CONCLUSIONS: These data show that in human immunodeficiency virus-positive patients with brain mass lesions, SBB has a high diagnostic yield. A subgroup of patients will benefit from specific therapy guided by the SBB result. The procedure should, however, be strictly limited to patients able to tolerate specific therapy.

[Interventional neuroradiologic procedures]. / Neuroangiographie thérapeutique.

Intracranial aneurysms, cervical carotid stenosis and acute cerebral ischemia constitute the three main and more frequent diseases in which the endovascular approach is considered a valuable alternative to the surgical or pharmacologic treatment. With the introduction of balloon assistance techniques, even intracranial large neck aneurysms can be currently suitable to endovascular treatment. Stent angioplasty is widely used in whole Europe in the treatment of cervical carotid artery stenosis. Mechanical endovascular embolectomy techniques are actually available to be used alone or in combination with pharmacologic thrombolysis in the treatment of acute cerebral ischemia. This article discuss on the new technical possibilities concerning the endovascular approach in these aforementioned diseases.

Nitric oxide synthase inhibition by L-NAME prevents brain acidosis during focal cerebral ischemia in rabbits.

This experiment examined the effects of nitric oxide (NO) synthase inhibition on brain intracellular pH, regional cortical blood flow, and NADH fluorescence before and during 3 h of focal cerebral ischemia using in vivo fluorescence imaging. Thirty fasted rabbits under 1% halothane were divided into four treatment groups receiving N omega-nitro-L-arginine methyl ester (L-NAME) intravenously at 20 min prior to ischemia (0.1, 1, and 10 mg/kg and 1 mg/kg + 5 mg/kg L-arginine) and two control groups (nonischemic and ischemic). In ischemic controls, brain pH(i), declined to 6.73 +/- 0.03 at 30 min and remained acidotic through the remainder of the ischemic period. In the 0.1 mg/kg group, brain pH(i) fell after 30 min of ischemia to 6.76 +/- 0.05 (p < 0.05), but then improved progressively despite occlusion. In the 1 mg/kg group, brain pH(i), remained normal despite middle cerebral artery (MCA) occlusion. In the 10 mg/kg group and in the combined L-NAME + L-arginine group, pH(i) fell after 30 min of ischemia to 6.81 +/- 0.03 (p < 0.05) and remained acidotic. During occlusion, regional cortical blood flow dropped in a dose-dependent manner. After 3 h of ischemia, regional cortical blood flow was 33.9 +/- 10.9 and 25.1 +/- 8.9 ml/100 g/min at doses of 0.1 and 10.0 mg/kg, respectively, L-NAME treatment did not significantly alter the increased NADH fluorescence that accompanied occlusion. This study shows that L-NAME can prevent intracellular brain acidosis during focal cerebral ischemia independent from regional cortical blood flow changes. This experiment suggests that NO is involved in pH(i) regulation during focal cerebral ischemia.

Astrocyte-specific expression of aquaporin-9 in mouse brain is increased after transient focal cerebral ischemia.

Aquaporin-9 (AQP9) is a new member of the aquaporin family of water-selective channels mainly expressed in liver and testis, presenting the characteristic of also being permeable to various solutes, particularly lactate. Recent data have shown the presence of AQP9 on tanycytes in the rat brain. In the current study, the authors show the expression of AQP9 in astrocytes in the mouse brain and changes in its expression after cerebral ischemia. Indeed, in control mouse, the AQP9 immunolabeling is present on astrocytic processes bordering the subarachnoid space and ventricles. The labeling also is observed on astrocytes in the white matter, hippocampus, hypothalamus, and lateral septum. After focal transient ischemia, an increase of the immunolabeling is detected on astrocytes in periinfarct areas. This AQP9 distribution study in mouse brain suggests a role of AQP9 in water homeostasis in the central nervous system. Furthermore, the overexpression of AQP9 on astrocytes surrounding an ischemic lesion suggests that AQP9 may also play a role in the regulation of postischemia edema and, in view of its permeability to monocarboxylates, in the clearance of lactate from the ischemic focus.

Magnetic resonance imaging with gadolinium contrast agent in small deep (lacunar) cerebral infarcts.

OBJECTIVE: To assess gadolinium-diethylenetriamine-pentaacetic acid (Gd-DTPA) contrast-enhanced magnetic resonance (MR) imaging as an index of recent symptomatic small deep cerebral infarcts (SDCIs). DESIGN: Prospective case series. SETTINGS: Primary-care center. PATIENTS: Thirty-one consecutive patients presenting with the clinical diagnosis of SDCI in the territory of the perforators of the internal carotid artery or the vertebrobasilar system and confirmed by MR imaging. INTERVENTION: Rapid intravenous infusion of Gd-DTPA 5 to 10 minutes prior to acquisition of T1-weighted images. MAIN OUTCOME MEASURES: Precise clinicotopographic correlation on MR scans. RESULTS: Non-contrast-enhanced MR imaging allowed precise clinicotopographic correlation in five (38%) of 13 patients with SDCI symptoms in the internal carotid artery territory. After Gd-DTPA administration, precise clinicotopographic correlation improved in 11 (85%) of 13 patients. In five patients, precise correlation was possible only after Gd-DTPA enhancement. Nonenhanced MR imaging allowed precise clinicotopographic correlation in 15 (83%) of 18 patients with SDCI symptoms in the vertebrobasilar territory. After Gd-DTPA administration, we could establish precise clinicotopographic correlation in all patients with SDCIs in the vertebrobasilar territory. In three patients, precise correlation was possible only after Gd-DTPA contrast enhancement. In seven (23%) of 31 patients, Gd-DTPA failed to enhance symptomatic lesion: in five patients MR scans were performed early (less than 7 days) and in two patients later in the course (greater than 7 days). CONCLUSIONS: Although Gd-DTPA administration is unlikely to improve the sensitivity of MR images in visualizing SDCIs, it significantly improves the rate of precise clinicoanatomic correlation. All enhancing lesions showed precise clinicotopographic correlation. Enhancement may be absent in the acute phase (less than 7 days).

Distribution and possible roles of aquaporin 9 in the brain.

Aquaporin 9 (AQP9) is a member of the aquaporin channel family involved in water flux through plasma membranes and exhibits the distinct feature of being also permeable to monocarboxylates, such as lactate, and various solutes, including glycerol, carbamides, purines, pyrimidines, and urea. AQP9 is constitutively expressed at high levels in the liver. In the brain under physiological conditions, AQP9 was first observed in tanycytes, and then in astrocytes. Only recently, its expression was also shown in neurons. Neurons expressing AQP9 are catecholaminergic and glucose sensitive. The expression of neuronal AQP9 can be negatively regulated by insulin and in diabetic animals an increase in AQP9 expression is observed in the catecholaminergic nuclei of the hindbrain, similar to the regulation of AQP9 by insulin in the liver. Furthermore, after transient brain ischemia, AQP9 expression is increased in astrocytes and its regulation may implicate the MAP-kinase pathways stimulated in such pathological conditions. Despite these new data, the exact role of AQP9 in the brain is still unclear. However, we may hypothesize that AQP9 is implicated in brain energy metabolism, as a neutral solute channel. AQP9 could facilitate the diffusion of lactate from the astrocyte to the neuron. In glucose sensitive neurons, diffusion of lactate and glycerol could stimulate these neurons in a similar manner to glucose and could regulate the energy balance. In pathological conditions, induction of AQP9 in astrocytes could participate in the clearance of excess lactate in the extracellular space. These hypotheses concerning the function of brain AQP9 are still speculative and open new areas of investigation.