The influence of aneurysm morphology on the volume of hemorrhage after rupture.

OBJECTIVE: Factors determining the risk of rupture of intracranial aneurysms have been extensively studied; however, little attention is paid to variables influencing the volume of bleeding after rupture. In this study the authors aimed to evaluate the impact of aneurysm morphological variables on the amount of hemorrhage. METHODS: This was a retrospective cohort analysis of a prospectively collected data set of 116 patients presenting at a single center with subarachnoid hemorrhage due to aneurysmal rupture. A volumetric assessment of the total hemorrhage volume was performed from the initial noncontrast CT. Aneurysms were segmented and reproduced from the initial CT angiography study, and morphology indexes were calculated with a computer-assisted approach. Clinical and demographic characteristics of the patients were included in the study. Factors influencing the volume of hemorrhage were explored with univariate correlations, multiple linear regression analysis, and graphical probabilistic modeling. RESULTS: The univariate analysis demonstrated that several of the morphological variables but only the patient's age from the clinical-demographic variables correlated (p < 0.05) with the volume of bleeding. Nine morphological variables correlated positively (absolute height, perpendicular height, maximum width, sac surface area, sac volume, size ratio, bottleneck factor, neck-to-vessel ratio, and width-to-vessel ratio) and two correlated negatively (parent vessel average diameter and the aneurysm angle). After multivariate analysis, only the aneurysm size ratio (p < 0.001) and the patient's age (p = 0.023) remained statistically significant. The graphical probabilistic model confirmed the size ratio and the patient's age as the variables most related to the total hemorrhage volume. CONCLUSIONS: A greater aneurysm size ratio and an older patient age are likely to entail a greater volume of bleeding after subarachnoid hemorrhage.

Reliability and accuracy assessment of morphometric measurements obtained with software for three-dimensional reconstruction of brain aneurysms relative to cerebral angiography measures.

OBJECTIVE: To analyze the reliability and accuracy of morphological measurements of software employed to three-dimensionally reconstruct aneurysms and vessels (VMTKlab, version 1.6.1,) with computed tomography angiography (CTA) as the source of images. Agreement with measurements from three-dimensional digital subtraction angiography (3 D-DSA) was evaluated. METHODS: We evaluated 40 patients presenting with aneurysmal subarachnoid hemorrhage (aSAH). We analyzed four main variables of the aneurysm morphology: absolute height (size), neck (maximum neck width), perpendicular height, and maximum width. The CTA images were uploaded to the software and then segmented to reconstruct the aneurysm. This new method was compared to the current gold standard-3D reconstruction of pretreatment cerebral angiography. We used intraclass correlation coefficient (ICC) and Bland-Altman plot analyses to evaluate the agreement between these methods. RESULTS: The ICCs obtained for absolute height, neck, perpendicular height, and maximum width were 0.85, 0.57, 0.85, and 0.89, respectively. This implied good agreement except for the neck of the aneurysm (moderate agreement). Bland-Altman plots are presented for the four indexes. The average of the differences was not significant in terms of absolute height, perpendicular height, and maximum width indicating good agreement. However, it was significant for the neck of the aneurysm. CONCLUSIONS: We report good agreement between the values generated using VMTKlab and cerebral angiography for three of the four main variables. Discrepancies in neck diameter are not surprising and its underestimation with a traditional delineation from cerebral angiography has been reported before.

Assessment of Collateral Circulation Using Perfusion CT in Middle Cerebral Artery Thrombectomy-Treated Patients.

INTRODUCTION: The prognostic value of leptomeningeal collateral circulation in thrombectomy-treated patients remains unclear. We evaluated the construct validity of assessing leptomeningeal collateral circulation using a new regional perfusion CT source image-based approach, the Perfusion Acquisition for THrombectomy Scale (PATHS). We also compared the prognostic value of PATHS with a further 6 scales based on various techniques: CT-angiography, perfusion CT, and digital subtraction angiography. Additionally, we studied the relationship between the scores for the different scales. PATIENTS AND METHODS: We performed a retrospective study of consecutive patients with stroke and M1/terminal carotid occlusion treated with thrombectomy in our center. Leptomeningeal collateral circulation was prospectively evaluated using 7 scales: Tan and Miteff (CT Angiography); Calleja, Cao, American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology, and PATHS (perfusion); and Christoforidis (Digital Subtraction Angiography). Correlations were studied using the Spearman method. RESULTS: The study population comprised 108 patients. All scales predicted the modified Rankin Scale at 3 months (P ≤ .02) and all but 1 (Christoforidis) correlated with 24-hour brain infarct volume (P ≤ .02). These correlations were higher with PATHS (rho = -0.47, P < .001 for 3-month modified Rankin Scale; rho = -0.35, P < .001 for follow-up infarct volume). The multivariate analysis showed PATHS to be an independent predictor of modified Rankin Scale at 3 months less than equal to 2. A crosscorrelation analysis revealed a better correlation between scales that used the same techniques. CONCLUSIONS: PATHS can be used to assess leptomeningeal collateral circulation. PATHS had better prognostic value than other scales; therefore, it might be considered for assessment of leptomeningeal collateral circulation in candidates for thrombectomy. The moderate correlation between scales suggests that scores are not interchangeable.

Influence of CYP450 Enzymes, CES1, PON1, ABCB1, and P2RY12 Polymorphisms on Clopidogrel Response in Patients Subjected to a Percutaneous Neurointervention.

PURPOSE: Clopidogrel is a thienopyridine prodrug that inhibits platelet aggregation. It is prescribed to prevent atherothrombotic and thromboembolic events in patients receiving a stent implant in carotid, vertebral, or cranial arteries. The influence of cytochrome P-450 (CYP) 2C19 on the response to clopidogrel has been widely studied; however, the effect of other genes involved in clopidogrel absorption and metabolism has not been established in this cohort of patients. METHODS: This observational retrospective study assessed the antiplatelet response and the prevalence of hemorrhagic or ischemic events after percutaneous neurointervention in clopidogrel-treated patients, related to 35 polymorphisms in the genes encoding the clopidogrel-metabolizing enzymes (CYP2C19, CYP1A2, CYP2B6, CYP2C9, CYP2C9, CYP3A4, CYP3A5, carboxylesterase-1 [CES1], and paraoxonase-1 [PON1]), P-glycoprotein transporter (ABCB1), and platelet receptor P2Y12. Polymorphisms were analyzed by quantitative real-time polymerase chain reaction and matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. Antiplatelet response was documented with the VerifyNow system (Accriva, San Diego, California). FINDINGS: We confirmed that CYP2C19 is the most important enzyme involved in clopidogrel response. The carriage of the CYP2C19*2 allele was strongly associated with hyporesponse to clopidogrel, while the CYP2C19*17 allele was a protective factor for the development of ischemic events (odds ratio = 0.149; P = 0.002) but a risk factor for bleeding (odds ratio = 3.60; P = 0.038). Patients carrying ABCB1 mutated alleles showed lower aggregation values, suggesting that clopidogrel absorption is influenced by P-glycoprotein. In fact, the percentage of responders was significantly higher in the group carrying the mutated haplotype compared to the wild type (80.8% vs 43.3%; P = 0.009). Patients with the CES1 G143E C/T genotype showed a considerably lower, aggregation value versus wild-type patients, although the difference was not significant likely due to the small sample size (59.0 [21.2] vs 165.2 [86.0] PRU; P = 0.084), which suggests an increased active metabolite formation. No relationship was found between polymorphisms in other CYP genes, PON1, or P2RY12 and response to clopidogrel in patients subjected to neurointervention procedures. IMPLICATIONS: Therapeutic guidelines recommend that CYP2C19 intermediate and poor metabolizers with acute coronary syndromes undergoing percutaneous coronary intervention receive an alternative antiplatelet therapy; however, genotype-guided therapy is not a standard recommendation for neurovascular conditions. This is the first study to carry out a joint analysis of CYP2C19 and other genes involved in clopidogrel treatment in patients receiving percutaneous neurointervention. Our findings support routine genotyping in clopidogrel-treated patients. Moreover, we encourage considering an alternative antiplatelet therapy in CYP2C19 intermediate, poor and ultrarapid metabolizers. Additionally, ABCB1 polymorphisms could be considered for a better pharmacogenetic approach.

Preservation of Residual Hearing After Cochlear Implant Surgery With Deep Insertion Electrode Arrays.

OBJECTIVE: To evaluate the hearing preservation (HP) in cochlear implant (CI) recipients who did not fulfill the criteria for electric acoustic stimulation (EAS). STUDY DESIGN: Prospective study SETTING:: Tertiary academic hospital. PATIENTS: Adults undergoing CI with deep insertion electrode arrays who had measurable residual hearing (RH) before surgery. INTERVENTION: Demographic data, surgical technique, pure-tone average, and radiological findings were evaluated. MAIN OUTCOME MEASURE: Pre- and postoperative pure-tone audiometry. A preservation study was therefore performed for the whole range of frequencies (THP), and for low frequencies (LFHP). RESULTS: From the total 25 patients who underwent the surgical procedure, 6 of them (26.08%) did not retain any RH and 17 of them (73.91%) had some degree of HP. A clear association was observed between the use of the atraumatic technique (AT) and the percentage of some degree of HP. In patients who underwent the AT, LFHP was 72.79% and THP was 70.40%. In patients who did not undergo the technique, LFHP was 31.48% (p: 0.003) and THP was 23.50% (p: 0.002). LFHP was complete or partial (more than 25% of initial RH) in 92.3% of patients who underwent AT and in 50% of those who did not. Radiological findings showed that complete insertion is not associated with poorer HP. CONCLUSION: If the appropriate technique is used, preservation of RH is feasible after cochlear implant surgery with deep insertion electrode arrays.

Influence of CYP2C19 Phenotype on the Effect of Clopidogrel in Patients Undergoing a Percutaneous Neurointervention Procedure.

This observational retrospective study assessed the antiplatelet response and clinical events after clopidogrel treatment in patients who underwent percutaneous neurointervention, related to CYP2C19 metabolizer status (normal (NM), intermediate/poor (IM-PM), and ultrarapid (UM); inferred from *2, *3, and *17 allele determination). From 123 patients, IM-PM had a higher aggregation value (201.1 vs. 137.6 NM, 149.4 UM, P < 0.05) and lower response rate (37.5% vs. 69.8% NM, 61.1% UM), along with higher treatment change rate (25% vs. 5.7% NM, 10.5% UM). The highest ischemic events incidence occurred in NM (11.3% vs. 6.3% IM, 10.5% UM) and hemorrhagic events in UM (13.2% vs. 0% IM and 3.8% NM). No differences were found regarding ischemic event onset time, while hemorrhagic event frequency in UM was higher with shorter onset time (P = 0.047). CYP2C19 no-function and increased function alleles defined the clopidogrel response. UM patients had increased bleeding risk. Therapeutic recommendations should include dose reduction or treatment change in UM.

Mechanical thrombectomy in orally anticoagulated patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: To investigate the efficacy and safety of mechanical thrombectomy in patients with acute ischemic stroke according to the oral anticoagulation medication taken at the time of stroke onset. MATERIALS AND METHODS: A retrospective multicenter study of prospectively collected data based on data from the registry the Madrid Stroke Network was performed. We included consecutive patients with acute ischemic stroke treated with mechanical thrombectomy and compared the frequency of intracranial hemorrhage and the modified Rankin Scale (mRS) score at 3 months according to anticoagulation status. RESULTS: The study population comprised 502 patients, of whom 389 (77.5%) were not anticoagulated, 104 (20.7%) were taking vitamin K antagonists, and 9 (1.8%) were taking direct oral anticoagulants. Intravenous thrombolysis had been performed in 59.8% and 15.0% of non-anticoagulated and anticoagulated patients, respectively. Rates of intracranial hemorrhage after treatment were similar between non-anticoagulated and anticoagulated patients, as were rates of recanalization. After 3 months of follow-up, the mRS score was ≤2 in 56.3% and 55.7% of non-anticoagulated and anticoagulated patients, respectively (P=NS). Mortality rates were similar in the two groups (13.1%and12.4%, respectively). Among anticoagulated patients, no differences were found for intracranial bleeding, mRS score, or mortality rates between patients taking vitamin K antagonists and those taking direct oral anticoagulants. CONCLUSIONS: Mechanical thrombectomy is feasible in anticoagulated patients with acute ischemic stroke. The outcomes and safety profile are similar to those of patients with no prior anticoagulation therapy.

Futile Interhospital Transfer for Endovascular Treatment in Acute Ischemic Stroke: The Madrid Stroke Network Experience.

BACKGROUND AND PURPOSE: The complexity of endovascular revascularization treatment (ERT) in acute ischemic stroke and the small number of patients eligible for treatment justify the development of stroke center networks with interhospital patient transfers. However, this approach might result in futile transfers (ie, the transfer of patients who ultimately do not undergo ERT). Our aim was to analyze the frequency of these futile transfers and the reasons for discarding ERT and to identify the possible associated factors. METHODS: We analyzed an observational prospective ERT registry from a stroke collaboration ERT network consisting of 3 hospitals. There were interhospital transfers from the first attending hospital to the on-call ERT center for the patients for whom this therapy was indicated, either primarily or after intravenous thrombolysis (drip and shift). RESULTS: The ERT protocol was activated for 199 patients, 129 of whom underwent ERT (64.8%). A total of 120 (60.3%) patients required a hospital transfer, 50 of whom (41%) ultimately did not undergo ERT. There were no differences in their baseline characteristics, the times from stroke onset, or in the delays in interhospital transfers between the transferred patients who were treated and those who were not treated. The main reasons for rejecting ERT after the interhospital transfer were clinical improvement/arterial recanalization (48%) and neuroimaging criteria (32%). CONCLUSIONS: Forty-one percent of the ERT transfers were futile, but none of the baseline patient characteristics predicted this result. Futility could be reduced if repetition of unnecessary diagnostic tests was avoided.

Intrasellar chordoma associated with a primitive persistent trigeminal artery.

Chordomas located primarily in the sellar region are uncommon, and may be misdiagnosed non-functioning pituitary adenoma. Furthermore, the association of a persistent primitive trigeminal artery (PPTA) with an intrasellar chordoma is extremely rare, and no similar cases have been reported in the literature to date. The coexistence of intrasellar chordoma (ISC) and PPTA makes safe and complete tumor resection challenging, and preoperative endovascular occlusion of this artery may be helpful. We report a case of a 32-year-old man who developed right hemifacial paresthesias and a cranial nerve six palsy. MRI study demonstrated the presence of a primary ISC associated with a PPTA. Angiographic balloon test occlusion of the PPTA revealed no neurological changes, so this vessel was endovascularly occluded by coiling. The lesion was subtotally removed through a sublabial transsphenoidal approach, without intraoperative bleeding complications. Histological examination of the lesion was consistent with the diagnosis of chordoma. Detailed preoperative neurovascular evaluation may be useful to detect vascular anomalies associated with intracranial chordomas, such as PPTA. In this report we emphasize the importance of appropriate treatment of vascular anomalies prior intrasellar lesions resection that may facilitate surgery and avoid potential hazardous intraoperative bleeding complications.

B-function expression in the flower center underlies the homeotic phenotype of Lacandonia schismatica (Triuridaceae).

Spontaneous homeotic transformations have been described in natural populations of both plants and animals, but little is known about the molecular-genetic mechanisms underlying these processes in plants. In the ABC model of floral organ identity in Arabidopsis thaliana, the B- and C-functions are necessary for stamen morphogenesis, and C alone is required for carpel identity. We provide ABC model-based molecular-genetic evidence that explains the unique inside-out homeotic floral organ arrangement of the monocotyledonous mycoheterotroph species Lacandonia schismatica (Triuridaceae) from Mexico. Whereas a quarter million flowering plant species bear central carpels surrounded by stamens, L. schismatica stamens occur in the center of the flower and are surrounded by carpels. The simplest explanation for this is that the B-function is displaced toward the flower center. Our analyses of the spatio-temporal pattern of B- and C-function gene expression are consistent with this hypothesis. The hypothesis is further supported by conservation between the B-function genes of L. schismatica and Arabidopsis, as the former are able to rescue stamens in Arabidopsis transgenic complementation lines, and Ls-AP3 and Ls-PI are able to interact with each other and with the corresponding Arabidopsis B-function proteins in yeast. Thus, relatively simple molecular modifications may underlie important morphological shifts in natural populations of extant plant taxa.