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1.
Cancer Med ; 12(16): 17340-17345, 2023 08.
Article in English | MEDLINE | ID: mdl-37466344

ABSTRACT

OBJECTIVE: Accurate, easily accessible and economically viable cancer diagnostic tools are pivotal in improving the abysmal 5% survival rate of pancreatic cancer. METHODS: A novel, affordable, non-invasive diagnostic method has been developed by combining measurement precision of infrared spectroscopy with classification using machine learning tools. RESULTS: Diagnosis accuracy as high as 90% has been achieved. The study investigated urine and blood from pancreas cancer patients and healthy volunteers, and significantly improved accuracy by focusing on sweet-spots within blood plasma fractions containing molecules within a narrow range of molecular weights.


Subject(s)
Pancreatic Neoplasms , Humans , Spectroscopy, Fourier Transform Infrared/methods , Pancreatic Neoplasms/diagnosis , Machine Learning , Pancreatic Neoplasms
2.
Front Pharmacol ; 14: 1287487, 2023.
Article in English | MEDLINE | ID: mdl-38178859

ABSTRACT

Background: The kallikrein kinin system (KKS) is an established pharmacological target for the treatment and prevention of attacks in hereditary angioedema (HAE). Proteolytic activities of FXIIa and single-chain Factor XII (FXII) zymogen contribute to KKS activation and thereby may play roles in both initiating and propagating HAE attacks. In this report, we investigated the effects of potent small molecule FXIIa inhibitors on FXIIa and single chain FXII enzymatic activities, KKS activation, and angioedema in mice. Methods: We examined the effects of 29 structurally distinct FXIIa inhibitors on enzymatic activities of FXIIa and a mutant single chain FXII with R334A, R343A and R353A substitutions (rFXII-T), that does not undergo zymogen conversion to FXIIa, using kinetic fluorogenic substrate assays. We examined the effects of a representative FXIIa inhibitor, KV998086, on KKS activation and both carrageenan- and captopril-induced angioedema in mice. Results: FXIIa inhibitors designed to target its catalytic domain also potently inhibited the enzymatic activity of rFXII-T and the pIC50s of these compounds linearly correlated for rFXIIa and rFXII-T (R 2 = 0.93). KV998086, a potent oral FXIIa inhibitor (IC50 = 7.2 nM) inhibited dextran sulfate (DXS)-stimulated generation of plasma kallikrein and FXIIa, and the cleavage of high molecular weight kininogen (HK) in human plasma. KV998086 also inhibited rFXII-T mediated HK cleavage (p < 0.005) in plasma from FXII knockout mice supplemented with rFXII-T and stimulated with polyphosphate or DXS. Orally administered KV998086 protected mice from 1) captopril-induced Evans blue leakage in colon and laryngotracheal tissues and 2) blocked carrageenan-induced plasma HK consumption and paw edema. Conclusion: These findings show that small molecule FXIIa inhibitors, designed to target its active site, also inhibit the enzymatic activity of FXII zymogen. Combined inhibition of FXII zymogen and FXIIa may thereby suppress both the initiation and amplification of KKS activation that contribute to hereditary angioedema attacks and other FXII-mediated diseases.

3.
Anal Chem ; 94(40): 13642-13646, 2022 10 11.
Article in English | MEDLINE | ID: mdl-36161799

ABSTRACT

We report a novel method with higher than 90% accuracy in diagnosing buccal mucosa cancer. We use Fourier transform infrared spectroscopic analysis of human serum by suppressing confounding high molecular weight signals, thus relatively enhancing the biomarkers' signals. A narrower range molecular weight window of the serum was also investigated that yielded even higher accuracy on diagnosis. The most accurate results were produced in the serum's 10-30 kDa molecular weight region to distinguish between the two hardest to discern classes, i.e., premalignant and cancer patients. This work promises an avenue for earlier diagnosis with high accuracy as well as greater insight into the molecular origins of these signals by identifying a key molecular weight region to focus on.


Subject(s)
Mouth Mucosa , Mouth Neoplasms , Fourier Analysis , Humans , Mouth Neoplasms/diagnosis , Spectroscopy, Fourier Transform Infrared/methods , Vibration
4.
Clin Exp Allergy ; 52(9): 1059-1070, 2022 09.
Article in English | MEDLINE | ID: mdl-35278245

ABSTRACT

BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease that leads to recurrent episodes of swelling and pain caused by uncontrolled plasma kallikrein (PKa) activity. Current guidelines recommend ready availability of on-demand HAE treatments that can be administered early upon attack onset. This report describes the pharmacological and pharmacodynamic properties of the novel oral small-molecule PKa inhibitor KVD900 as a potential on-demand treatment for HAE. METHODS: Pharmacological properties of KVD900 on PKa and closely related serine proteases were characterized using kinetic fluorogenic substrate activity assays. Effects of KVD900 on PKa activity and kallikrein kinin system activation in whole plasma were measured in the presence of dextran sulphate (DXS)-stimulation using a fluorogenic substrate and capillary immunoassays to quantify high molecular weight kininogen (HK), plasma prekallikrein and Factor XII cleavage. Pharmacodynamic effects of orally administered KVD900 were characterized in plasma samples from six healthy controls in a first in human phase 1 clinical trial and from 12 participants with HAE in a phase 2 clinical trial. RESULTS: KVD900 is a selective, competitive and reversible inhibitor of human PKa enzyme with a Ki of 3.02 nM. The association constant (Kon ) of KVD900 for PKa is >10 × 106  M-1  s-1 . Oral administration of KVD900 in a first-in-human clinical trial achieved rapid and near complete inhibition of DXS-stimulated PKa enzyme activity and HK cleavage and reduced plasma prekallikrein and Factor XII activation in plasma. In individuals with HAE, orally administered KVD900 inhibited DXS-stimulated PKa activity in plasma by ≥95% from 45 min to at least 4 h post-dose and provided rapid protection of HK from cleavage. CONCLUSION: KVD900 is a fast-acting oral PKa inhibitor that rapidly inhibits PKa activity, kallikrein kinin system activation and HK cleavage in plasma. On-demand administration of KVD900 may provide an opportunity to halt the generation of bradykinin and reverse HAE attacks.


Subject(s)
Angioedemas, Hereditary , Angioedemas, Hereditary/drug therapy , Angioedemas, Hereditary/prevention & control , Bradykinin , Complement C1 Inhibitor Protein/genetics , Factor XII , Fluorescent Dyes/therapeutic use , Humans , Kallikrein-Kinin System , Plasma Kallikrein , Prekallikrein/metabolism
5.
J Allergy Clin Immunol ; 149(6): 2034-2042, 2022 06.
Article in English | MEDLINE | ID: mdl-35086692

ABSTRACT

BACKGROUND: Attacks of hereditary angioedema are attributed to excessive plasma kallikrein (PKa) activity, which cleaves high-molecular-weight kininogen to generate the proinflammatory hormone bradykinin. OBJECTIVE: We evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of KVD900, an orally administered inhibitor of PKa in healthy adults. METHODS: KVD900 was administered in 2 clinical studies. In the first study, healthy adult men received single ascending doses (5-600 mg) of KVD900 capsule or placebo, single 100 mg doses of KVD900 tablet and KVD900 capsule (crossover), and single 600 mg doses of KVD900 (6 × 100 mg tablets) under fed and fasting conditions (crossover). In a second study, 3 cohorts of healthy adults were provided 600 mg of KVD900 tablets at 8-, 4-, and 2-hour intervals. RESULTS: Overall, 98 healthy participants received KVD900. All adverse events (AEs) were mild, except for a single moderate AE (headache). Exposure to KVD900 was proportional to dose. The PK parameters for KVD900 600 mg in tablet form under fasted conditions were mean (coefficient of variation) maximum plasma concentration of 6460 (22.0) ng/mL, mean (coefficient of variation) area under the curve (AUC0-24) of 18,600 (22.5) h⋅ng/mL, and median (range) time to maximum plasma concentration of 0.5 (0.33-1.5) hours. Mean PKa inhibition was essentially complete (>98%) between 20 minutes and 3 hours, and >90% inhibition was maintained for at least 8 hours after dosing. High-molecular-weight kininogen cleavage protection at the 600 mg dose was attained within 20 minutes and maintained for 8 to 10 hours. CONCLUSION: These phase 1 studies evaluated the PK/PD profile of KVD900, showing that KVD900 rapidly achieves near-complete PKa inhibition and is generally safe and well tolerated. GOV IDENTIFIER: NCT04349800.


Subject(s)
Angioedemas, Hereditary , Administration, Oral , Adult , Angioedemas, Hereditary/drug therapy , Area Under Curve , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Healthy Volunteers , Humans , Kininogen, High-Molecular-Weight , Male , Tablets
6.
J Neurosurg ; 135(5): 1385-1393, 2021 Mar 19.
Article in English | MEDLINE | ID: mdl-33740759

ABSTRACT

OBJECTIVE: In select patients, extracranial-intracranial (EC-IC) bypass remains an important tool for cerebral revascularization. Traditionally, superficial temporal artery-middle cerebral artery (STA-MCA) bypass was performed using one limb of the STA only. In an attempt to augment flow and to direct flow to different ischemic areas of the brain, the authors adopted a "double-barrel" technique in which both branches of the STA are used to revascularize distinct MCA territories. METHODS: A series of consecutive double-barrel STA-MCA bypasses performed between 2010 and 2020 were reviewed. Each anastomosis was directed to augment flow to a territory most at risk based on preoperative perfusion studies, cerebral angiography, and intraoperative indocyanine green data. CT perfusion and CTA were routinely used to evaluate postoperative augmentation and graft patency. Patient perioperative outcomes, surgical complications, and modified Rankin Scale (mRS) scores at the last follow-up were reported. RESULTS: Forty-four patients (16 males, 28 females) successfully underwent double-barrel STA-MCA bypass on 54 cerebral hemispheres: 28 operations were for moyamoya disease, 23 for atherosclerotic disease refractory to medical therapy, 2 for complex cerebral aneurysms, and 1 for carotid occlusion as a sequela of cavernous meningioma growth. Ten patients underwent multiple operations, 9 of whom had moyamoya disease/syndrome, with the subsequent operation on the contralateral hemisphere. The average patient age at surgery was 45.1 years (range 14-73 years), with a mean follow-up time of 22.1 months. Intraoperative graft patency was confirmed in 100% of cases, and 101 (98.1%) of the 103 anastomoses with imaging follow-up were patent. Perfusion to the revascularized hemisphere was improved in 88.2% of cases. Perioperative ischemic and hemorrhagic complications occurred in 8 procedures (2 were asymptomatic), whereas remote ischemic and hemorrhagic events occurred in 7 cases. There was no mortality in the series, and the mean patient mRS scores were 1.72 at presentation and 1.15 at the last follow-up. CONCLUSIONS: The high rates of intraoperative and postoperative patency support the feasibility of dual-anastomosis STA-MCA bypass for revascularization. The perioperative complication rate is not significantly different from that of single-anastomosis bypass. The functional outcomes at follow-up and perfusion improvement postoperatively support the efficacy and safety of this method as a treatment strategy.

7.
World Neurosurg ; 141: e743-e751, 2020 09.
Article in English | MEDLINE | ID: mdl-32534265

ABSTRACT

BACKGROUND: Extracranial-to-intracranial bypass surgery is a well-established technique that has been practiced for over 50 years. Since then, numerous technical variants have developed nationally and internationally. OBJECTIVE: Based on a survey, to collect information on cerebrovascular bypass surgeons and their background, surgical volume, and technical steps of extracranial-to-intracranial bypasses with focus on superficial temporal artery to middle cerebral artery (STA-MCA) bypass. METHODS: An electronic survey was distributed among bypass neurosurgeons. Responses were analyzed for national-international variations of STA-MCA bypass surgery techniques. The survey focused on the technical aspects of the surgery itself rather than patient selection or perioperative management. RESULTS: Survey responses were collected from 51 neurosurgeons performing cerebrovascular bypass, from 11 different countries across North America, Europe, and Asia. The largest age block was early-to mid-career (66.7% aged 36-50 years). Most participating surgeons (80.40%) performed less than 20 bypasses annually, whereas a select few surgeons (3) performed more than 50 annually. The most common bypass was STA-M4 MCA bypass with a linear incision (34%) over the parietal branch (44%) and choosing an MCA recipient based on diameter (61.2%). The interrupted anastomosis technique was most common (74%). CONCLUSIONS: The results of this electronic survey will help to identify common patterns in STA-MCA bypass surgery and will serve as a guide to other neurosurgeons to modify and improve their technique. Cerebrovascular bypass is still widely practiced, including by young neurosurgeons, who are actively learning from established masters who share their experience.


Subject(s)
Cerebral Revascularization/methods , Microsurgery/methods , Neurosurgeons , Neurosurgical Procedures/methods , Surveys and Questionnaires , Adult , Female , Humans , Male , Middle Aged
8.
World Neurosurg ; 140: e234-e239, 2020 08.
Article in English | MEDLINE | ID: mdl-32407912

ABSTRACT

OBJECTIVE: Triplicate A2 segment of the anterior cerebral artery is a rare anatomical variant (1%-3% prevalence) that which is thought to result mainly from persistence of the embryonic median artery of the corpus callosum. We sought to determine whether the triple-A2 variant is specifically associated with anterior communicating artery (ACoA) aneurysm. METHODS: We reviewed 2-dimensional digital-subtraction angiography (2D-DSA) as well as 3-dimensional rotational angiography (3D-RA) images of 55 patients with ACoA aneurysms who presented for evaluation and treatment between 2009 and 2014 at our institution. The criteria for definitively obtaining an accurate accounting of all A2 segments was presence of adequate cross-filling across the ACoA on 2D-DSA or 3D-RA imaging, or ability to fuse left and right 3D-RA images. Patients whose imaging did not meet these criteria were excluded from further analysis. RESULTS: We obtained a definitive count of all A2 segments in 36 patients. Among these, 19 patients (5 with the triple-A2 variant) were treated surgically, and 17 patients (2 with the triple-A2 variant) were treated endovascularly. The triple-A2 variant was seen in 7 patients. The prevalence of triple-A2 variant among patients with ACoA aneurysm was 19.4%. Patients with ACoA aneurysms had a significantly higher prevalence of the triple-A2 variant compared with the general population (P < 0.00001). CONCLUSIONS: Compared with the normal population, patients with ACoA aneurysms deemed to require treatment have a significantly higher likelihood of having triplicate A2 segment. Knowledge of this anatomical variation is of critical importance in planning and executing endovascular and microsurgical treatment of ACoA aneurysms.


Subject(s)
Anterior Cerebral Artery/abnormalities , Intracranial Aneurysm/pathology , Adolescent , Adult , Aged , Angiography, Digital Subtraction , Anterior Cerebral Artery/diagnostic imaging , Cerebral Angiography , Female , Humans , Intracranial Aneurysm/surgery , Male , Middle Aged , Young Adult
9.
J Neurol Surg B Skull Base ; 81(1): 62-67, 2020 Feb.
Article in English | MEDLINE | ID: mdl-32021751

ABSTRACT

Introduction Several adjunctive osteal skull base maneuvers have been proposed to increase surgical exposure of the anterolateral approach. However, one of the easiest methods does not involve bone: the interfascial temporalis muscle dissection. Methods Sequential dissections were performed bilaterally on five fixed silicone-injected cadaver heads. The amount of sphenoid drilling, scalp retraction, and brain retraction was standardized in all specimens. For each approach, surgical angles were measured for four deep targets: the tip of the anterior clinoid process, the internal carotid artery terminus, the origin of the posterior communicating artery, and the anterior communicating artery. Five surgical angles were measured for each target. Results There were increases on the order of 20% in the anteroposterior (AP)-mid, AP-lateral, and mediolateral-anterior angles for all deep targets with interfascial approach versus a myocutaneous flap. An orbitozygomatic osteotomy additionally increased almost all the angles, but incrementally less so. Conclusion An interfascial dissection increases the surgical exposure to a larger degree than additional osteotomies for several surgically relevant working angles. The addition of an orbitozygomatic osteotomy affords a particular benefit for the suprachiasmatic region. Increased adoption of interfascial mobilization or the temporalis muscle-an easily performed and low-risk maneuver-during anterolateral craniotomies may obviate the need for more involved skull base drilling.

10.
World Neurosurg ; 134: e16-e28, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31470147

ABSTRACT

BACKGROUND: Flow diversion has become increasingly popular for treatment of cerebral aneurysms in the past few years. In an increasing number of patients with aneurysms, flow diversion (FD) has failed, with a paucity of reported data regarding salvage treatment for these challenging cases. METHODS: We present a multicenter series of 13 aneurysms for which FD failed and that were subsequently treated with open surgery. We also present a review of the reported data regarding operative management of aneurysms after unsuccessful FD. RESULTS: Twelve patients with 13 aneurysms were included in the present study. All 12 patients had undergone surgery after FD because of persistent aneurysm filling, mass effect, or aneurysm rupture. The patients underwent aneurysm clipping and parent vessel reconstruction, decompression of the aneurysm mass, occlusion of proximal flow to the aneurysm, or aneurysm trapping with or without extracranial-intracranial artery bypass. CONCLUSIONS: Aneurysms for which FD fails present a variety of unique and challenging management situations that will likely be encountered with increased frequency, given the popularity of FD. Microsurgical salvage options require individualized care tailored to the underlying pathological features, patient characteristics, and surgical expertise.


Subject(s)
Aneurysm, Ruptured/surgery , Endovascular Procedures , Intracranial Aneurysm/surgery , Neurosurgical Procedures , Adult , Aged , Cerebral Revascularization/methods , Female , Humans , Male , Middle Aged , Treatment Outcome
11.
Interv Neuroradiol ; 25(1): 102-110, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30231798

ABSTRACT

OBJECTIVE: Contrast-enhanced cone-beam computed tomography (CBCT) imaging is commonly used for evaluating neurovascular stents and their relationship to the parent artery or vascular pathologies such as arteriovenous malformations (AVMs) and dural arteriovenous fistulas (dAVFs) in the context of surrounding anatomical structures. The purpose of this study was to understand the effects of varying concentrations of contrast medium used in CBCT imaging for optimal visualization of various endovascular devices and anatomical pathologies. METHODS: Thirty-five patients with various neurovascular pathologies were included in the study. Contrast-enhanced CBCT images (20 s DR, Siemens syngo DynaCT, Siemens AG, Forchheim, Germany) were acquired in all cases, with varying dilutions of contrast medium, from 1% to 30%. The injection rate was kept constant at 3 cc/sec with an X-ray delay of two sec, and a total volume of 66 cc of diluted contrast was administered. Results from visual and quantitative analysis were reported. RESULTS: Ten percent dilution of contrast medium resulted in the best image differentiation between flow-diverter devices and the parent artery. Concentrations as low as 2.5% contrast medium also resulted in identifying AVMs in the context of the surrounding brain parenchyma, whereas 20% to 30% dilution provided the best visualization of residual AVMs with prior Onyx embolization and dAVFs in the presence of bony structures. CONCLUSIONS: Simultaneous visualization of brain parenchyma, bony structures, devices, and pathological anatomy using contrast-enhanced CBCT imaging is feasible with appropriate doses of iodinated contrast, and should be tailored to the individual case based on the goals of CBCT.


Subject(s)
Cerebrovascular Disorders/diagnostic imaging , Cone-Beam Computed Tomography/methods , Contrast Media/administration & dosage , Iohexol/administration & dosage , Blood Vessel Prosthesis , Cerebrovascular Disorders/therapy , Diagnosis, Differential , Dose-Response Relationship, Drug , Humans
13.
Cureus ; 10(3): e2381, 2018 Mar 28.
Article in English | MEDLINE | ID: mdl-29850376

ABSTRACT

Giant cavernous aneurysms of the internal carotid artery (ICA) are challenging lesions associated with high surgical morbidity. Prior to the past several years, these were treated by surgical reconstruction, proximal ligation, or stent-assisted coiling techniques. Flow diversion has become the standard of care for these lesions, providing a high rate of obliteration with a much better safety profile. However, flow diverters rely upon a navigable vasculature and, usually, a tri-axial support system. Cases in which such access is difficult require unique approaches to combine the strengths of both surgical and endovascular therapy. A woman with a giant cavernous ICA aneurysm and an ophthalmic artery aneurysm presented for treatment, but access was challenging due to cervical ICA tortuosity and pseudoaneurysms. We elected a staged, combined approach with surgical reconstruction of the cervical ICA followed by flow diverter placement for the intracranial aneurysms. Our case features an "outside-the-box" approach that synergistically applied both microsurgical and endovascular techniques to treat a challenging pathology. Classic microsurgical techniques remain important in cases that are refractory or not amenable to endovascular therapy alone.

14.
Cureus ; 10(2): e2192, 2018 Feb 14.
Article in English | MEDLINE | ID: mdl-29682431

ABSTRACT

The transcavernous approach to the basilar artery, as initially described by Dolenc, is one of the most common and elegant approaches to the region. It affords a generous working and viewing angle, but it can be technically challenging and requires attention to detail at each step. We investigate this approach in this report via a cadaveric prosection with a focus on the value of each of the component steps in improving surgical view and exposure. The transcavernous approach steps are divided into extradural stages: orbitozygomatic osteotomy (a modern adjunct to Dolenc's original description), drilling of the lesser sphenoid wing, and anterior clinoidectomy; and intradural stages: wide splitting of the Sylvian fissure, unroofing of the oculomotor and trochlear nerves, and posterior clinoidectomy. The surgical windows afforded by each step in the approach are illustrated using microscopic images taken during the cadaveric prosection of a donor who happened to harbor a basilar apex aneurysm. An illustrative case and artist illustrations are used to emphasize the relative value of each step of the transcavernous exposure.

15.
Oper Neurosurg (Hagerstown) ; 14(3): 288-294, 2018 03 01.
Article in English | MEDLINE | ID: mdl-28961997

ABSTRACT

BACKGROUND: Traditionally, superficial temporal artery-middle cerebral artery (STA-MCA) bypass uses one STA branch. Its augmentation of flow has classically been described as "low flow." In a double-barrel STA-MCA bypass, however, both branches of the STA are utilized. Here we hypothesize that this should not be considered "low flow." OBJECTIVE: To review quantitative flow data from our cases and investigate the impact of double-barrel STA-MCA bypass on total flow augmentation, and to assess whether double-barrel STA-MCA bypass might be useful in situations that traditionally demand more complex bypass strategies. METHODS: Intraoperative flow probe measurements from STA-MCA bypass cases were retrospectively tabulated and compared. Cut flow and bypass flow measurements were, respectively, taken before and after completion of anastomoses. The higher value was labeled best observed flow (BOF). RESULTS: We identified 21 STA-MCA bypass cases with available intraoperative flow probe measurements, of which 17 utilized double-barrel technique. Only 1 STA branch was available in 4 cases. Significantly higher average BOF was seen when utilizing 2 STA branches (69 vs 39 cc/min, P < .001). A majority (9/17) of double-barrel bypasses provided BOF ≥ 65 cc/min (120 cc/min maximum). The single branch bypass maximum BOF was 40 cc/min. CONCLUSION: Double-barrel bypass technique significantly enhances STA-MCA flow capacity and may be useful in situations in which a high-flow bypass is needed. The 2 efferent limbs allow flexibility in distributing flow across separate at-risk territories. The method compares favorably to other descriptions of high-flow bypass without the morbidity of graft harvest or an additional cervical incision.


Subject(s)
Cerebral Revascularization/methods , Middle Cerebral Artery/surgery , Temporal Arteries/surgery , Humans , Registries , Retrospective Studies
16.
J Neurosurg ; 129(1): 114-120, 2018 07.
Article in English | MEDLINE | ID: mdl-28820309

ABSTRACT

OBJECTIVE The evaluation of the venous neurovasculature, especially the dural venous sinuses, is most often performed using MR or CT venography. For further assessment, diagnostic cerebral angiography may be performed. Three-dimensional rotational angiography (3D-RA) can be applied to the venous system, producing 3D rotational venography (3D-RV) and cross-sectional reconstructions, which function as an adjunct to traditional 2D digital subtraction angiography. METHODS After querying the database of Baylor St. Luke's Medical Center in Houston, Texas, the authors reviewed the radiological and clinical data of patients who underwent 3D-RV. This modality was performed based on standard techniques for 3D-RA, with the catheter placed in the internal carotid artery and a longer x-ray delay calculated based on time difference between the early arterial phase and the venous phase. RESULTS Of the 12 cases reviewed, 5 patients had neoplasms invading a venous sinus, 4 patients with idiopathic intracranial hypertension required evaluation of venous sinus stenosis, 2 patients had venous diverticula, and 1 patient had a posterior fossa arachnoid cyst. The x-ray delay ranged from 7 to 10 seconds. The 3D-RV was used both for diagnosis and in treatment planning. CONCLUSIONS Three-dimensional RV and associated cross-sectional reconstructions can be used to assess the cerebral venous vasculature in a manner distinct from established modalities. Three-dimensional RV can be performed with relative ease on widely available biplane equipment, and data can be processed using standard software packages. The authors present the protocol and technique used along with potential applications to venous sinus stenosis, venous diverticula, and tumors invading the venous sinuses.


Subject(s)
Angiography, Digital Subtraction , Cerebral Veins/diagnostic imaging , Cerebrovascular Disorders/diagnostic imaging , Cone-Beam Computed Tomography , Imaging, Three-Dimensional , Phlebography/methods , Adult , Aged , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
17.
J Neurointerv Surg ; 10(2): 122-126, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28265011

ABSTRACT

BACKGROUND: The Pipeline Embolization Device (PED) is increasingly used for both on- and off-label purposes for treatment of intracranial aneurysms. The device gradually slows flow of blood into the aneurysm, but the high metal coverage of PED promotes endothelialization of the device. Occasionally, this leads to in-stent stenosis that is clinically well tolerated. We present a multi-institutional Pipeline series that includes three cases of gradual asymptomatic occlusion within the PED and parent vessel. METHODS: Institutional databases at each participating center were searched for patients treated with the PED. Patients with at least 50% stenosis or occlusion were selected and all relevant clinical and radiographic data were reviewed. RESULTS: A total of 326 cases performed by five neurointerventionalists across four institutions were reviewed. Among these there were three cases of complete occlusion and two cases of stenosis of more than 50%, for an occlusion rate of 0.9%. All patients were clinically asymptomatic. CONCLUSIONS: A gradual tourniquet-like occlusion can occur following placement of the PED, leading to vessel occlusion. This has been clinically well tolerated by patients in our series due to the formation of pial collaterals as the stenosis progresses, likely due to ischemic preconditioning. Small parent vessel, pre-existing stenosis, fusiform pathology, overlapping devices, and suboptimal antiplatelet therapy seem to be predisposing factors. Further experience and follow-up will allow us to characterize the risk factors and optimize post-procedural therapy for these patients.


Subject(s)
Cerebrovascular Disorders/diagnostic imaging , Embolization, Therapeutic/adverse effects , Intracranial Aneurysm/diagnostic imaging , Intracranial Aneurysm/therapy , Stents/adverse effects , Adult , Aged , Cerebral Angiography/trends , Cerebrovascular Disorders/etiology , Embolization, Therapeutic/instrumentation , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications/diagnostic imaging , Postoperative Complications/etiology , Retrospective Studies , Tourniquets , Treatment Outcome
18.
Oper Neurosurg (Hagerstown) ; 13(6): 739-745, 2017 12 01.
Article in English | MEDLINE | ID: mdl-29186602

ABSTRACT

BACKGROUND: Intraoperative computed tomography angiography (ICTA) is a novel completion imaging modality for carotid endarterectomy (CEA). No studies exist in the literature describing ICTA use in CEA. OBJECTIVE: To evaluate the feasibility and efficacy of ICTA as a method of immediately evaluating the technical results of CEA. METHODS: Twenty-three consecutive CEAs were performed by a single neurosurgeon over an 8-month period. Of this series, 12 utilized ICTA for completion imaging, 10 utilized duplex ultrasonography (US), and 1 utilized no intraoperative completion imaging. Electronic medical records were reviewed to assess demographics, CTA results, US results, and need for revisions. RESULTS: Patients included 13 men (62%) and 8 women (38%). All patients had symptomatic internal carotid artery stenosis. Polytetrafluoroethylene (PTFE) patch angioplasty was used in 16 cases (70%). Average operative times were comparable between cases that utilized CTA and US, 180 and 175 min, respectively. Major technical defects were identified in one of the 12 cases utilizing ICTA and none of the 10 cases utilizing intraoperative US. The technical defect was revised without subsequent neurological complication. One patient had a postoperative intracerebral hemorrhage requiring surgical evacuation. Fifteen patients were followed for up to 3 months with no postoperative stroke or transient ischemic attacks. CONCLUSION: ICTA is a potentially safe and effective completion imaging modality compared to traditional alternatives, enabling the identification of technical deficits intraoperatively. While no statistically significant difference in operative times were noted between intraoperative CTA and US use, numerous steps must be taken to maximize the efficiency of ICTA.


Subject(s)
Carotid Stenosis/diagnostic imaging , Carotid Stenosis/surgery , Computed Tomography Angiography , Endarterectomy, Carotid/methods , Monitoring, Intraoperative/methods , Aged , Angiography, Digital Subtraction , Female , Humans , Magnetic Resonance Angiography , Male , Middle Aged , Monitoring, Intraoperative/instrumentation
20.
Neurosurgery ; 81(5): 795-802, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-28328002

ABSTRACT

BACKGROUND: Patients with strokes from M2 segment middle cerebral artery (MCA) occlusion have been underrepresented in recent randomized trials of endovascular therapy. OBJECTIVE: To better understand the clinical, imaging, and procedural predictors of successful recanalization and clinical outcomes in this population of patients. METHODS: We performed a multicenter retrospective analysis of consecutive patients with acute MCA M2 segment occlusion who underwent thrombectomy with stent retrievers or primary aspiration thrombectomy (including A Direct Aspiration First Pass Technique approach). We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics. RESULTS: One hundred and seventeen patients were included in analysis (median admission National Institutes of Health stroke scale [NIHSS] score 15, mean age 67.0 ± 14.5, 42% females). Good clinical outcome at 3 months (modified Rankin scale [mRS] ≤ 2) was achieved in 56% of patients. Treatment beyond 6 h of symptoms onset (P = .69, OR 0.80, 95% CI 0.38-1.73) and age over 80 (P = .47, OR 0.65, 95% CI 0.25-1.70) were not predictive of poor outcome. NIHSS > 15 was a strong predictor of clinical outcome, based on mRS distribution at 3 months (P = .0085, OR 0.35, 95% CI 0.16-0.74). Direct aspiration and primary stent retriever thrombectomy approaches showed similar radiographic and clinical success rates. CONCLUSION: Advanced age and time to treatment beyond 6 h from symptom onset were not predictive of clinical outcome with thrombectomy. NIHSS score above 15 was a strong predictor of outcome. Direct aspiration and primary stent retriever thrombectomy showed similar efficacy.


Subject(s)
Endovascular Procedures/methods , Infarction, Middle Cerebral Artery/surgery , Stroke/surgery , Thrombectomy/methods , Aged , Female , Humans , Male , Middle Aged , Middle Cerebral Artery/surgery , Retrospective Studies , Stents/adverse effects , Treatment Outcome
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