Clinical uncertainty in large vessel occlusion ischemic stroke: does automated perfusion imaging make a difference? An intra-rater and inter-rater agreement study.

BACKGROUND: Limited research exists regarding the impact of neuroimaging on endovascular thrombectomy (EVT) decisions for late-window cases of large vessel occlusion (LVO) stroke. OBJECTIVE: T0 assess whether perfusion CT imaging: (1) alters the proportion of recommendations for EVT, and (2) enhances the reliability of EVT decision-making compared with non-contrast CT and CT angiography. METHODS: We conducted a survey using 30 patients drawn from an institutional database of 3144 acute stroke cases. These were presented to 29 Canadian physicians with and without perfusion imaging. We used non-overlapping 95% confidence intervals and difference in agreement classification as criteria to suggest a difference between the Gwet AC1 statistics (κG). RESULTS: The percentage of EVT recommendations differed by 1.1% with or without perfusion imaging. Individual decisions changed in 21.4% of cases (11.3% against EVT and 10.1% in favor). Inter-rater agreement (κG) among the 29 raters was similar between non-perfusion and perfusion CT neuroimaging (κG=0.487; 95% CI 0.327 to 0.647 and κG=0.552; 95% CI 0.430 to 0.675). The 95% CIs overlapped with moderate agreement in both. Intra-rater agreement exhibited overlapping 95% CIs for all 28 raters. κG was either substantial or excellent (0.81-1) for 71.4% (20/28) of raters in both groups. CONCLUSIONS: Despite the minimal difference in overall EVT recommendations with either neuroimaging protocol one in five decisions changed with perfusion imaging. Regarding agreement we found that the use of automated CT perfusion images does not significantly impact the reliability of EVT decisions for patients with late-window LVO.

Nonaneurysmal perimesencephalic subarachnoid hemorrhage on noncontrast head CT: An accuracy, inter-rater, and intra-rater reliability study.

BACKGROUND AND PURPOSE: To evaluate the reliability and accuracy of nonaneurysmal perimesencephalic subarachnoid hemorrhage (NAPSAH) on Noncontrast Head CT (NCCT) between numerous raters. MATERIALS AND METHODS: 45 NCCT of adult patients with SAH who also had a catheter angiography (CA) were independently evaluated by 48 diverse raters; 45 raters performed a second assessment one month later. For each case, raters were asked: 1) whether they judged the bleeding pattern to be perimesencephalic; 2) whether there was blood anterior to brainstem; 3) complete filling of the anterior interhemispheric fissure (AIF); 4) extension to the lateral part of the sylvian fissure (LSF); 5) frank intraventricular hemorrhage; 6) whether in the hypothetical presence of a negative CT angiogram they would still recommend CA. An automatic NAPSAH diagnosis was also generated by combining responses to questions 2-5. Reliability was estimated using Gwet's AC1 (κG), and the relationship between the NCCT diagnosis of NAPSAH and the recommendation to perform CA using Cramer's V test. Multi-rater accuracy of NCCT in predicting negative CA was explored. RESULTS: Inter-rater reliability for the presence of NAPSAH was moderate (κG = 0.58; 95%CI: 0.47, 0.69), but improved to substantial when automatically generated (κG = 0.70; 95%CI: 0.59, 0.81). The most reliable criteria were the absence of AIF filling (κG = 0.79) and extension to LSF (κG = 0.79). Mean intra-rater reliability was substantial (κG = 0.65). NAPSAH weakly correlated with CA decision (V = 0.50). Mean sensitivity and specificity were 58% (95%CI: 44%, 71%) and 83 % (95%CI: 72 %, 94%), respectively. CONCLUSION: NAPSAH remains a diagnosis of exclusion. The NCCT diagnosis was moderately reliable and its impact on clinical decisions modest.

Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors.

BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Designer molecules of the synaptic organizer MDGA1 reveal 3D conformational control of biological function.

MDGAs (MAM domain-containing glycosylphosphatidylinositol anchors) are synaptic cell surface molecules that regulate the formation of trans-synaptic bridges between neurexins (NRXNs) and neuroligins (NLGNs), which promote synaptic development. Mutations in MDGAs are implicated in various neuropsychiatric diseases. MDGAs bind NLGNs in cis on the postsynaptic membrane and physically block NLGNs from binding to NRXNs. In crystal structures, the six immunoglobulin (Ig) and single fibronectin III domains of MDGA1 reveal a striking compact, triangular shape, both alone and in complex with NLGNs. Whether this unusual domain arrangement is required for biological function or other arrangements occur with different functional outcomes is unknown. Here, we show that WT MDGA1 can adopt both compact and extended 3D conformations that bind NLGN2. Designer mutants targeting strategic molecular elbows in MDGA1 alter the distribution of 3D conformations while leaving the binding affinity between soluble ectodomains of MDGA1 and NLGN2 intact. In contrast, in a cellular context, these mutants result in unique combinations of functional consequences, including altered binding to NLGN2, decreased capacity to conceal NLGN2 from NRXN1ß, and/or suppressed NLGN2-mediated inhibitory presynaptic differentiation, despite the mutations being located far from the MDGA1-NLGN2 interaction site. Thus, the 3D conformation of the entire MDGA1 ectodomain appears critical for its function, and its NLGN-binding site on Ig1-Ig2 is not independent of the rest of the molecule. As a result, global 3D conformational changes to the MDGA1 ectodomain via strategic elbows may form a molecular mechanism to regulate MDGA1 action within the synaptic cleft.

Activation of a hypothalamus-habenula circuit by mechanical stimulation inhibits cocaine addiction-like behaviors

BACKGROUND: Mechanoreceptor activation modulates GABA neuron firing and dopamine (DA) release in the mesolimbic DA system, an area implicated in reward and substance abuse. The lateral habenula (LHb), the lateral hypothalamus (LH), and the mesolimbic DA system are not only reciprocally connected, but also involved in drug reward. We explored the effects of mechanical stimulation (MS) on cocaine addiction-like behaviors and the role of the LH-LHb circuit in the MS effects. MS was performed over ulnar nerve and the effects were evaluated by using drug seeking behaviors, optogenetics, chemogenetics, electrophysiology and immunohistochemistry. RESULTS: Mechanical stimulation attenuated locomotor activity in a nerve-dependent manner and 50-kHz ultrasonic vocalizations (USVs) and DA release in nucleus accumbens (NAc) following cocaine injection. The MS effects were ablated by electrolytic lesion or optogenetic inhibition of LHb. Optogenetic activation of LHb suppressed cocaine-enhanced 50 kHz USVs and locomotion. MS reversed cocaine suppression of neuronal activity of LHb. MS also inhibited cocaine-primed reinstatement of drug-seeking behavior, which was blocked by chemogenetic inhibition of an LH-LHb circuit. CONCLUSION: These findings suggest that peripheral mechanical stimulation activates LH-LHb pathways to attenuate cocaine-induced psychomotor responses and seeking behaviors.

Chemically targeting the redox switch in AP1 transcription factor ΔFOSB.

The AP1 transcription factor ΔFOSB, a splice variant of FOSB, accumulates in the brain in response to chronic insults such as exposure to drugs of abuse, depression, Alzheimer's disease and tardive dyskinesias, and mediates subsequent long-term neuroadaptations. ΔFOSB forms heterodimers with other AP1 transcription factors, e.g. JUND, that bind DNA under control of a putative cysteine-based redox switch. Here, we reveal the structural basis of the redox switch by determining a key missing crystal structure in a trio, the ΔFOSB/JUND bZIP domains in the reduced, DNA-free form. Screening a cysteine-focused library containing 3200 thiol-reactive compounds, we identify specific compounds that target the redox switch, validate their activity biochemically and in cell-based assays, and show that they are well tolerated in different cell lines despite their general potential to bind to cysteines covalently. A crystal structure of the ΔFOSB/JUND bZIP domains in complex with a redox-switch-targeting compound reveals a deep compound-binding pocket near the DNA-binding site. We demonstrate that ΔFOSB, and potentially other, related AP1 transcription factors, can be targeted specifically and discriminately by exploiting unique structural features such as the redox switch and the binding partner to modulate biological function despite these proteins previously being thought to be undruggable.

An Increase in Peripheral Temperature following Cocaine Administration Is Mediated through Activation of Dopamine D2 Receptor in Rats.

Drug addiction has become a worldwide problem, affecting millions of people across the globe. While the majority of mechanistic studies on drug addiction have been focused on the central nervous system, including the mesolimbic dopamine system, the peripheral actions of drugs of abuse remain largely unknown. Our preliminary study found that the systemic injection of cocaine increased peripheral skin temperature. This led us to our present study, which investigated the mechanisms underlying the increase in peripheral temperature following cocaine injection. Male Sprague Dawley rats were anesthetized with pentobarbital sodium, and peripheral skin temperature measurements were taken using a thermocouple needle microprobe and an infrared thermal camera. Cocaine injection caused an acute rise in peripheral body temperature, but not core body temperature, about 10 min after injection, and the temperature increases were occluded by systemic injection of dopamine D2 receptor antagonist L741,626, but not D1 receptor antagonist SCH23390. In addition, systemic administration of bromocriptine, a dopamine D2 receptor agonist, significantly increased peripheral temperature. Infrared thermal imaging showed that the thermal increases following cocaine injection were predominantly in the distal areas of the forelimbs and hindlimbs, relative to core body temperature. Treatment with cocaine or bromocriptine decreased the size of skin blood vessels without affecting the expression of dopamine D2 receptors. These results suggest that increased peripheral temperature in skin following cocaine injection is associated with the activation of the dopamine D2 receptor.

When Two Is Better than One : The Buddy-wire Technique in Flow-diversion Procedures.

BACKGROUND: Delivery of most flow diverters (FD) requires larger, and thus stiffer microcatheters (0.021-0.027in.) which can pose challenges to intracranial navigation. The concomitant use of two microwires within one microcatheter, also known as the buddy-wire technique, may be helpful for navigation and support in challenging situations. METHODS: We analyzed all flow diverter procedures in our prospectively collected database. We recorded all patient-related, anatomical and procedural information. We performed univariate statistics and technical descriptions. RESULTS: In total, 208 consecutive patients treated with a FD at our institution between July 2014 and August 2020 were retrospectively analyzed. In 17 patients the buddy-wire technique was used (mean age 63 years, range 31-87 years: 16 female). Aneurysms were located at the petrous, cavernous, supraophthalmic internal carotid artery, and a proximal M2 branch in 2, 7, 7 and 1 patient(s), respectively. In all cases a 0.027in. microcatheter was used for device deployment. In 14 patients with a wide-necked aneurysm the buddy-wire provided additional support to advance the microcatheter and mitigated the ledge between the aneurysm neck and the parent artery or a side branch. In two giant cavernous aneurysms treated with telescoping FDs, the buddy-wire was used to re-enter the proximal end of the foreshortened FD. CONCLUSION: The buddy-wire is a useful technique in FD procedures to prevent herniation of the microcatheter into the aneurysm sack, in wide-necked aneurysms to mitigate the ledge effect between the aneurysm neck and the parent artery where the microcatheter tip may get stuck, or to enable re-entry into a foreshortened FD.

Endovascular treatment of cavernous carotid artery aneurysms: A 10-year, single-center experience.

BACKGROUND: Cavernous carotid artery aneurysms can be treated by several endovascular techniques including flow diversion (FD) and parent vessel occlusion (PVO). We reviewed our institution's consecutive series of endovascularly treated cavernous carotid artery aneurysms to compare these two modalities and their associated clinical and radiographic outcomes. METHODS: All patients harboring a cavernous carotid artery aneurysm treated by FD or PVO from January 2008 to December 2018 were enrolled. Data were collected retrospectively and analyzed on patient presentation, aneurysm dimensions, treatments and related complications, rate of aneurysm occlusion, sac regression, and outcomes. RESULTS: Fourteen patients were treated with FD and 12 underwent PVO subsequent to passing a balloon test occlusion. There was no significant difference between treatment modalities in aneurysmal occlusion (97.0 ± 8.4% (FD) vs. 100% (PVO), p = 0.23), degree of sac regression (62.5 ± 16.7% (FD) vs. 56.8 ± 24.3% (PVO), p = 0.49), or near-complete to complete symptom improvement (66.7% (FD) vs. 81.8% (PVO), p = 0.62). Major complications included subarachnoid hemorrhage from aneurysmal rupture in 1 (7.1%) patient post-FD and 2 (16.7%) ischemic strokes following PVO. CONCLUSIONS: Endovascular treatment of cavernous carotid artery aneurysms by FD or PVO are both effective and safe. There is insufficient evidence to recommend one technique over the other and decision making should be individualized to the patient, their aneurysm morphology, and operator experience.

Subarachnoid Hemorrhage in Mechanical Thrombectomy for Acute Ischemic Stroke: Analysis of the STRATIS Registry, Systematic Review, and Meta-Analysis.

Background: The indications for mechanical thrombectomy in acute ischemic stroke continue to broaden, leading neurointerventionalists to treat vessel occlusions at increasingly distal locations farther in time from stroke onset. Accessing these smaller vessels raises the concern of iatrogenic subarachnoid hemorrhage (SAH) owing to increasing complexity in device navigation and retrieval. This study aims to determine the prevalence of SAH following mechanical thrombectomy, associated predictors, and resulting functional outcomes using a multicenter registry and compare this with a systematic review and meta-analysis of the literature. Methods: Data from STRATIS (The Systematic Evaluation of Patients Treated with Neurothrombectomy Devices for Acute Ischemic Stroke) registry were analyzed dichotomized by the presence or absence of SAH after thrombectomy. Only patients with 24-h post-procedural neuroimaging were included (n = 841). Multivariable logistic regression was performed to identify significant predictors of SAH. A systematic review and random-effects meta-analysis was also conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) protocol. Results: The prevalence of post-thrombectomy SAH was 5.23% in STRATIS with 15.9% (1.84% overall) experiencing neurological decline. Distal location of vessel occlusion (OR 3.41 [95% CI: 1.75-6.63], p < 0.001) and more than 3 device passes (OR 1.34 [95% CI: 1.09-1.64], p = 0.01) were associated with a higher probability of SAH in contrast to a reduction with administration of intravenous tissue plasminogen activator (tPA) (OR 0.48 [95% CI: 0.26-0.89], p = 0.02). There was a trend toward a higher discharge NIHSS (8.3 ± 8.7 vs. 5.3 ± 6.6, p = 0.07) with a significantly reduced proportion achieving functional independence at 90 days (modified Rankin Score 0-2: 32.5% vs. 57.8%, p = 0.002) in SAH patients. Pooled analysis of 10,126 patients from 6 randomized controlled trials and 64 observational studies demonstrated a prevalence of 5.85% [95% CI: 4.51-7.34%, I 2: 85.2%]. Only location of vessel occlusion was significant for increased odds of SAH at distal sites (OR 2.89 [95% CI: 1.14, 7.35]). Conclusions: Iatrogenic SAH related to mechanical thrombectomy is more common with treatment of distally-situated occlusions and multiple device passes. While low in overall prevalence, its effect is not benign with fewer patients reaching post-procedural functional independence, particularly if symptomatic.

Characteristics of pial brain arteriovenous malformations with transdural arterial supply.

PURPOSE: Transdural blood supply (TDBS) to pial brain arteriovenous malformations (BAVM) is uncommon and believed to be related to vascular endothelial growth factor - induced angiogenesis. The aim of this study was to define the BAVM characteristics in relation to presence and volume of TDBS. METHODS: BAVMs managed at our institution between January 2006 and December 2016 who subsequently underwent complete digital subtraction angiography (DSA) were included. They were classified based on presence of TDBS as well as volume of TDBS. RESULTS: Of the 641 BAVM patients managed during the recruitment period, 387 (391 BAVMs) had complete pretreatment DSAs. Forty-three (11.0 %, 10 ruptured) BAVMs exhibited TDBS. With TDBS group had a significantly greater proportion of large nidus (> 3.1 cm) than the Without TDBS group (85.1 % vs 19.5 %, p < 0.01) and were more frequently temporal (32.6 % vs 14.7 %, p < 0.01) and occipital (25.6 % vs 13.5 %, p < 0.05) in location. In unruptured BAVMs, the presence of headaches was significantly more prevalent when the malformation harboured TDBS compared to not (57.6 vs 34.8 %, p < 0.05). The annual rupture rate among unruptured BAVMs treated by conservative management was 4.7 % in the With TDBS (n = 12) group and 0% (n = 21) in BAVMs with TDBS that underwent treatment including surgery, endovascular therapy, or radiosurgery. CONCLUSION: BAVMs with TDBS are more likely to be associated with a large nidus and located in the temporal and occipital lobes. Headache is more frequently associated with the presence of TDBS. Rupture rate of unruptured BAVMS with TDBS can be effectively reduced following treatment.

Radial vs. Femoral Artery Access for Procedural Success in Diagnostic Cerebral Angiography : A Randomized Clinical Trial.

BACKGROUND AND PURPOSE: Radial artery access has become the standard of care in percutaneous coronary procedures due to demonstrated patient safety and comfort benefits; however, uptake of radial access for diagnostic cerebral angiography has been limited by practitioner concerns over the ability to achieve procedural success. We aimed to provide randomized clinical trial evidence for the non-inferiority of radial access to achieve procedural success. MATERIAL AND METHODS: Monocentric open label randomized controlled trial with a non-inferiority design and blinded primary outcome assessment. Adult patients referred in-hours for diagnostic cerebral angiography were eligible. Participants underwent permuted block randomization to radial or femoral artery access with an intention-to-treat analysis. The primary outcome was procedural success, defined as selective cannulation and/or diagnostic angiography of predetermined supra-aortic vessels of interest. The non-inferiority limit was 10.0%. Secondary outcomes included postprocedural complications, fluoroscopy and procedural times, radiation dose, contrast volume and rates of vertebral artery cannulation. RESULTS: A total of 80 participants were enrolled (female 42, male 38, mean age 47.0 years, radial access group n = 43, femoral n = 37). One patient in the radial group was excluded after enrollment due to insufficient sonographic radial artery internal diameter. Procedural success was achieved in 41 of 42 participants in the radial group (97.6%) and 36 of 37 in the femoral group (97.3%). The difference between groups was -0.3% (one-sided 95% confidence interval, CI 6.7%) and the null hypothesis was rejected. CONCLUSION: Radial artery access is non-inferior to femoral artery access for procedural success in cerebral angiography. A large multicenter trial is recommended as the next step.

Mutational Analysis of the Structure and Function of the Chaperoning Domain of UNC-45B.

UNC-45B is a multidomain molecular chaperone that is essential for the proper folding and assembly of myosin into muscle thick filaments in vivo. It has previously been demonstrated that the UCS domain is responsible for the chaperone-like properties of the UNC-45B. To better understand the chaperoning function of the UCS domain of the UNC-45B chaperone, we engineered mutations designed to 1) disrupt chaperone-client interactions by removing and altering the structure of a putative client-interacting loop and 2) disrupt chaperone-client interactions by changing highly conserved residues in a putative client-binding groove. We tested the effect of these mutations by using a, to our knowledge, novel combination of complementary biophysical assays (circular dichroism, chaperone activity, and small-angle x-ray scattering) and in vivo tools (Caenorhabditis elegans sarcomere structure). Removing the putative client-binding loop altered the secondary structure of the UCS domain (by decreasing the α-helix content), leading to a significant change in its solution conformation and a reduced chaperoning function. Additionally, we found that mutating several conserved residues in the putative client-binding groove did not alter the UCS domain secondary structure or structural stability but reduced its chaperoning activity. In vivo, these groove mutations were found to significantly alter the structure and organization of C. elegans sarcomeres. Furthermore, we tested the effect of R805W, a mutation distant from the putative client-binding region, which in humans, has been known to cause congenital and infantile cataracts. Our in vivo data show that, to our surprise, the R805W mutation appeared to have the most drastic detrimental effect on the structure and organization of the worm sarcomeres, indicating a crucial role of R805 in UCS-client interactions. Hence, our experimental approach combining biophysical and biological tools facilitates the study of myosin-chaperone interactions in mechanistic detail.

Highly Conserved Molecular Features in IgLONs Contrast Their Distinct Structural and Biological Outcomes.

Neuronal growth regulator 1 (NEGR1) and neurotrimin (NTM) are abundant cell-surface proteins found in the brain and form part of the IgLON (Immunoglobulin LSAMP, OBCAM, Neurotrimin) family. In humans, NEGR1 is implicated in obesity and mental disorders, while NTM is linked to intelligence and cognitive function. IgLONs dimerize homophilically and heterophilically, and they are thought to shape synaptic connections and neural circuits by acting in trans (spanning cellular junctions) and/or in cis (at the same side of a junction). Here, we reveal homodimeric structures of NEGR1 and NTM. They assemble into V-shaped complexes via their Ig1 domains, and disruption of the Ig1-Ig1 interface abolishes dimerization in solution. A hydrophobic ridge from one Ig1 domain inserts into a hydrophobic pocket from the opposing Ig1 domain producing an interaction interface that is highly conserved among IgLONs but remarkably plastic structurally. Given the high degree of sequence conservation at the interaction interface, we tested whether different IgLONs could elicit the same biological effect in vivo. In a small-scale study administering different soluble IgLONs directly into the brain and monitoring feeding, only NEGR1 altered food intake significantly. Taking NEGR1 as a prototype, our studies thus indicate that while IgLONs share a conserved mode of interaction and are able to bind each other as homomers and heteromers, they are structurally plastic and can exert unique biological action.

MRTFB suppresses colorectal cancer development through regulating SPDL1 and MCAM.

Myocardin-related transcription factor B (MRTFB) is a candidate tumor-suppressor gene identified in transposon mutagenesis screens of the intestine, liver, and pancreas. Using a combination of cell-based assays, in vivo tumor xenograft assays, and Mrtfb knockout mice, we demonstrate here that MRTFB is a human and mouse colorectal cancer (CRC) tumor suppressor that functions in part by inhibiting cell invasion and migration. To identify possible MRTFB transcriptional targets, we performed whole transcriptome RNA sequencing in MRTFB siRNA knockdown primary human colon cells and identified 15 differentially expressed genes. Among the top candidate tumor-suppressor targets were melanoma cell adhesion molecule (MCAM), a known tumor suppressor, and spindle apparatus coiled-coil protein 1 (SPDL1), which has no confirmed role in cancer. To determine whether these genes play a role in CRC, we knocked down the expression of MCAM and SPDL1 in human CRC cells and showed significantly increased invasion and migration of tumor cells. We also showed that Spdl1 expression is significantly down-regulated in Mrtfb knockout mouse intestine, while lower SPDL1 expression levels are significantly associated with reduced survival in CRC patients. Finally, we show that depletion of MCAM and SPDL1 in human CRC cells significantly increases tumor development in xenograft assays, further confirming their tumor-suppressive roles in CRC. Collectively, our findings demonstrate the tumor-suppressive role of MRTFB in CRC and identify several genes, including 2 tumor suppressors, that act downstream of MRTFB to regulate tumor growth and survival in CRC patients.

Clinical prediction of delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage.

OBJECTIVEThe aim of this study was to derive a clinically applicable decision rule using clinical, radiological, and laboratory data to predict the development of delayed cerebral ischemia (DCI) in aneurysmal subarachnoid hemorrhage (aSAH) patients.METHODSPatients presenting over a consecutive 9-year period with subarachnoid hemorrhage (SAH) and at least 1 angiographically evident aneurysm were included. Variables significantly associated with DCI in univariate analysis underwent multivariable logistic regression. Using the beta coefficients, points were assigned to each predictor to establish a scoring system with estimated risks. DCI was defined as neurological deterioration attributable to arterial narrowing detected by transcranial Doppler ultrasonography, CT angiography, MR angiography, or catheter angiography, after exclusion of competing diagnoses.RESULTSOf 463 patients, 58% experienced angiographic vasospasm with an overall DCI incidence of 21%. Age, modified Fisher grade, and ruptured aneurysm location were significantly associated with DCI. This combination of predictors had a greater area under the receiver operating characteristic curve than the modified Fisher grade alone (0.73 [95% CI 0.67-0.78] vs 0.66 [95% CI 0.60-0.71]). Patients 70 years or older with modified Fisher grade 0 or 1 SAH and a posterior circulation aneurysm had the lowest risk of DCI at 1.2% (0 points). The highest estimated risk was 38% (17 points) in patients 40-59 years old with modified Fisher grade 4 SAH following rupture of an anterior circulation aneurysm.CONCLUSIONSAmong patients presenting with aSAH, this score-based clinical prediction tool exhibits increased accuracy over the modified Fisher grade alone and may serve as a useful tool to individualize DCI risk.

Anesthesiologists' preferences for preoperative cardiac evaluation before vascular surgery: results of a mail survey.

STUDY OBJECTIVE: To investigate whether anesthesiologists' decisions to request preoperative cardiac evaluation (cardiologist consultation, echocardiography, and cardiac stress testing) before vascular surgery were influenced by patient comorbidity and magnitude of surgery; and to explore whether factors unrelated to the American College of Cardiology/American Heart Association (ACC/AHA) guidelines influence these decisions. DESIGN: Survey instrument. SETTING: University medical center. SUBJECTS: 2,000 U.S. anesthesiologists who were mailed a survey. MEASUREMENTS: Six factors in a hypothetical patient presenting for vascular surgery [gender, race (white vs. black), age (65 yrs vs. 85 yrs), comorbidities (sick vs. healthy), functional status, and magnitude of surgical stress] were evaluated. Respondents were asked about their demographics, practice patterns, and how they would manage the hypothetical patient. MAIN RESULTS: Of 2,000 mailed surveys, 439 U.S. anesthesiologists responded (22%). Multivariate ordinal logistic regression analysis showed that anesthesiologists were more likely to recommend preoperative cardiology consultation for patients with more comorbidities [odds ratio = 5.53; 95% confidence interval (CI) = 3.76, 8.15], for those with poorer functional status (odds ratio = 1.45; 95% CI = 1.02, 2.07), for those undergoing a more significant surgery (odds ratio = 1.61; 95% CI = 1.13, 2.30), as the clinicians' estimated risk of perioperative myocardial infarction increased (P < 0.001), or if they only infrequently anesthetized patients such as the one described in the scenario (P = 0.05). They also would request a preoperative echocardiogram for patients with more comorbidities (odds ratio = 2.58; 95% CI = 1.80, 3.68) and for those undergoing a more significant surgery (odds ratio = 1.59; 95% CI = 1.12, 2.25). A preoperative stress test was recommended for patients with more comorbidities (odds ratio = 3.01; 95% CI = 2.06, 4.38) and for those with a more significant surgery (odds ratio = 1.74; 95% CI = 1.15, 2.63). Other factors associated with request for a preoperative stress test were female gender of the anesthesiologist (odds ratio = 1.79; 95% CI = 1.11, 2.87), those with less experience with such patients (P = 0.05), and those from New England (odds ratio = 2.16; 95% CI = 1.01, 4.62). CONCLUSIONS: Anesthesiologists' preferences for preoperative cardiac evaluation are generally consistent with evidence-based and expert-based AHA/ACC guidelines. However, other physician factors (ie, gender, years in practice, and familiarity with the surgical procedure) also influenced these decisions.

Predictors of perioperative beta-blockade use in vascular surgery: a mail survey of United States anesthesiologists.

OBJECTIVES: It was hypothesized that anesthesiologists' decisions to provide perioperative beta-blockade during vascular surgery would be influenced more by physician factors than by those of their patients. DESIGN: Mail survey. SETTING: Case presentation. PARTICIPANTS: Four hundred thirty-nine anesthesiologists in the United States who responded to a survey. INTERVENTIONS: By using Microsoft Word Mail Merge (Microsoft, Redmond, WA), 6 factors in a hypothetical patient presenting for vascular surgery (sex, race, age, comorbidities, functional status, and magnitude of surgical stress) were randomly varied. MEASUREMENTS AND MAIN RESULTS: The response rate was 22%. Self-reported propensity to use beta-blockade was significantly increased among anesthesiologists who worked in New England, among those who worked in larger hospitals, or who had received fellowship training. Among healthy patients, beta-blockers were more likely to be used for older than younger patients. Among sicker patients, however, the reverse was true. Heart rate triggers for beta-blockade use were higher than heart rates associated with improved outcomes in pivotal beta-blocker trials. CONCLUSIONS: Preferences for perioperative beta-blockade use in vascular surgery patients are influenced by anesthesiologists' demographics as well as patient comorbidities or degree of surgical stress. This finding suggests that efforts to increase perioperative beta-blockade in high-risk vascular patients face significant barriers from some groups of clinicians.

The effects of inhibitory and facilitatory intracortical circuits on interhemispheric inhibition in the human motor cortex.

Inhibitory and facilitatory intracortical pathways regulating motor cortical output can be studied non-invasively in humans with transcranial magnetic stimulation. These circuits include short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). Stimulation of the motor cortex also inhibits the contralateral motor cortex (interhemispheric inhibition, IHI) at short (approximately 10 ms, IHI10) or long intervals (approximately 40 ms, IHI40). We investigated how SICI, ICF, and LICI influence IHI10 and IHI40. We hypothesize that intracortical circuits will have similar effects on IHI and cortical output neurons: SICI and LICI will decrease IHI, and ICF will increase it. Motor evoked potentials were recorded from the first dorsal interosseous muscles bilaterally in 10 healthy subjects. We compared IHI10 and IHI40 alone to IHI10 and IHI40 elicited in the presence of SICI, ICF, or LICI. Our results showed that SICI and LICI reduced IHI10, IHI40 and corticospinal output to a similar degree. ICF increased corticospinal output but had no effect on either IHI10 or IHI40. The different effects of ICF on corticospinal excitability and IHI suggest the transcallosal fibres mediating IHI and the corticospinal output system arise from different neuronal populations. SICI and LICI produce more global inhibition with similar effects on the transcallosal and descending corticospinal circuits.