KVD900, an oral on-demand treatment for hereditary angioedema: Phase 1 study results.

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.

Improving Vibrational Spectroscopy Prospects in Frontline Clinical Diagnosis: Fourier Transform Infrared on Buccal Mucosa Cancer.

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.

Pharmacological suppression of the kallikrein kinin system with KVD900: An orally available plasma kallikrein inhibitor for the on-demand treatment of hereditary angioedema.

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.

Clinical and Procedural Predictors of Outcomes From the Endovascular Treatment of Posterior Circulation Strokes.

BACKGROUND AND PURPOSE: Patients with posterior circulation strokes have been excluded from recent randomized endovascular stroke trials. We reviewed the recent multicenter experience with endovascular treatment of posterior circulation strokes to identify the clinical, radiographic, and procedural predictors of successful recanalization and good neurological outcomes. METHODS: We performed a multicenter retrospective analysis of consecutive patients with posterior circulation strokes, who underwent thrombectomy with stent retrievers or primary aspiration thrombectomy (including A Direct Aspiration First Pass Technique [ADAPT] approach). We correlated clinical and radiographic outcomes with demographic, clinical, and technical characteristics. RESULTS: A total of 100 patients were included in the final analysis (mean age, 63.5±14.2 years; mean admission National Institutes of Health Stroke Scale score, 19.2±8.2). Favorable clinical outcome at 3 months (modified Rankin Scale score ≤2) was achieved in 35% of patients. Successful recanalization and shorter time from stroke onset to the start of the procedure were significant predictors of favorable clinical outcome at 90 days. Stent retriever and aspiration thrombectomy as primary treatment approaches showed comparable procedural and clinical outcomes. None of the baseline advanced imaging modalities (magnetic resonance imaging, computed tomographic perfusion, or computed tomography angiography assessment of collaterals) showed superiority in selecting patients for thrombectomy. CONCLUSIONS: Time to the start of the procedure is an important predictor of clinical success after thrombectomy in patients with posterior circulation strokes. Both stent retriever and aspiration thrombectomy as primary treatment approaches are effective in achieving successful recanalization.

Frontline clinical diagnosis-FTIR on pancreatic cancer.

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.

Oral FXIIa inhibitor KV998086 suppresses FXIIa and single chain FXII mediated kallikrein kinin system activation.

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.

Double-barrel STA-MCA bypass for cerebral revascularization: lessons learned from a 10-year experience.

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.

Association of Anterior Communicating Artery Aneurysms with Triplicate A2 Segment of the Anterior Cerebral Artery.

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.

The Ultimate Skull Base Maneuver Does Not Involve Removing Bone: Quantifying the Benefits of the Interfascial Dissection.

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.

A Survey of Microsurgical Technique for Extracranial-to-Intracranial Bypass.

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.

Microsurgical Management of Intracranial Aneurysms After Failed Flow Diversion.

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.

Immune response in human cerebral cavernous malformations.

BACKGROUND AND PURPOSE: Preliminary observations suggesting the presence of B and plasma cells and oligoclonality of immunoglobulin (Ig) G in cerebral cavernous malformations (CCM) have motivated a systematic study correlating the infiltration of the immune cells with clinical activity and antigen-triggered immune response in surgically excised lesions. METHODS: Infiltration of plasma, B, T, and human leukocyte antigen-DR-expressing cells and macrophages within 23 excised CCM was related to clinical activity. Relative amounts of Ig isotypes were determined. IgG clonality of mRNA from CCM was assessed by spectratyping, cloning, and sequencing. RESULTS: Infiltration of the immune cells ranged widely within CCM lesions, and cells were generally coexpressed with each other. Immune cell infiltration did not associate with recent bleeding and lesion growth. Significantly more B lymphocytes in CCM lesions were associated with venous anomaly. More T cells were present in solitary lesions. More T cells and less macrophages were present in CCM from younger subjects. IgG isotype was present in all CCM lesions. Most lesions also expressed IgM and IgA, with IgM predominance over IgA correlating with recent CCM growth. Oligoclonality was shown in IgG mRNA from CCM, but not from peripheral blood lymphocytes, with only 8 complementary-determining region 3 sequences observed among 134 clones from 2 CCM lesions. CONCLUSIONS: An antigen-directed oligoclonal IgG immune response is present within CCM lesions regardless of recent clinical activity. Apparent differences in immune response in younger patients and in lesions with recent growth will need confirmation in other series. The pathogenicity of oligoclonal immune response will require systematic hypothesis testing in recently available CCM murine models.

Comparison between anterior cervical discectomy fusion and cervical corpectomy fusion using titanium cages for reconstruction: analysis of outcome and long-term follow-up.

Retrospective comparative study of 80 consecutive patients treated with either anterior cervical discectomy fusion (ACDF) or anterior cervical corpectomy fusion (ACCF) for multi-level cervical spondylosis. To compare clinical outcome, fusion rates, and complications of anterior cervical reconstruction of multi-level ACDF and single-/multi-level ACCF performed using titanium mesh cages (TMCs) filled with autograft and anterior cervical plates (ACPs). Reconstruction of the cervical spine after discectomy or corpectomy with titanium cages filled with autograft has become an acceptable alternative to both allograft and autograft; however, there is no data comparing the outcome of multi-level ACDF and single-/multi-level ACCF using this reconstruction. We evaluated 80 consecutive patients who underwent surgery for the treatment of multi-level cervical spondylosis at our institution from 1998 to 2001. In this series, 42 patients underwent multi-level ACDF (Group 1) and 38 patients underwent ACCF (Group 2). Interbody TMCs and local autograft bone with ACPs were used in both procedures. Medical records were reviewed to assess outcome. Clinical outcome was measured by Odom's criteria. Operative time and blood loss were noted. Radiographs were obtained at 6 and 12 weeks, 6 months, 1 year, and 2 years (if necessary). Early hardware failures and pseudarthroses were noted. Cervical sagittal curvature was measured by Ishihara's index at 1 year. Group 1 had a mean age 46.2 years (range 35-60 years). Group 2 had a mean age 50.1 years (range 35-70 years).The operative time was significantly lower (P < 0.001) and blood loss significantly higher (P < 0.001) in Group 2 than in Group 1. At a minimum of 1 year follow up, patients in both groups had equivalent improvement in their clinical symptoms. The fusion rates for Group 1 were 97.6 and 92.1% for Group 2. The rates of early hardware failure were higher in Group 2 (2.6%) than in Group 1 (0%). The fusion rates for Group 1 were not significantly higher than Group 2 (P > 0.28). There was one patient in Group 1 and 2 patients in Group 2 with pseudarthroses. Complication rates in Group 2 were not significantly higher (P > 0.341). Cervical lordosis was well-maintained (80%) in both groups. Both multi-level ACDF and ACCF with anterior cervical reconstruction using TMC filled with autograft and ACP for treatment of multi-level cervical spondylosis have high fusion rates and good clinical outcome. However, there is a higher rate of early hardware failure and pseudarthroses after ACCF than ACDF. Hence, in the absence of specific pathology requiring removal of vertebral body, multi-level ACDF using interbody cages and autologous bone graft could result in lower morbidity.

Lies, damned lies, and statistics: a neurosurgical perspective on the international randomized trial of extracranial to intracranial arterial bypass surgery.

The abrupt occurrence of a devastating stroke has been referred to as "super death." It has long been realized that ischemic cerebral vascular disease may become symptomatic with a wide variety of clinical patterns. A robust circle of Willis has been recognized for its major protective function in many cases. When it became possible to actually create new collateral circulation to the brain by microsurgical techniques, significant enthusiasm arose. This enthusiasm was interrupted by the negative results of the international randomized trial. Further analysis of the trial raised serious questions regarding incomplete randomization by contributors to the study, and there remains uncertainty about important potential benefits for some individuals. Long-term follow-up of 3 patients having different and complex circumstances is described to emphasize this concern. After the creation of reliable collateral circulation to the brain, none has experienced new ischemic deficit during the subsequent follow-up of 27, 25, and 12 years, respectively.

Optimizing contrast-enhanced cone-beam CT protocol to facilitate simultaneous visualization of neurovascular pathologies and surrounding structures of interest.

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.

Temporal bone dissection for neurosurgery residents: identifying the essential concepts and fundamental techniques for success.

BACKGROUND: Many contemporary neurosurgery residents, cordoned by work hour restrictions and drawn to newer technologies such as endovascular therapy, lack the proper direction necessary to learn the essentials of temporal bone dissection. A thorough knowledge of temporal bone anatomy combined with guidance regarding proper surgical technique makes temporal bone dissection an efficacious and fundamental learning activity. There is currently no concise guide for neurosurgical training programs to use in teaching the essentials of this dissection. METHODS: Over several years, the authors worked with neurosurgery residents to determine the key concepts necessary to gain a fundamental working knowledge of temporal bone dissection. RESULTS: We have identified 5 essential surgical principles and developed a step-by-step dissection technique useful for neurosurgery residents. CONCLUSIONS: Using this template, neurosurgery residents can make the most of their time in the skull base laboratory, becoming familiar with relevant temporal bone anatomy in situ and becoming facile with the surgical techniques necessary for its safe dissection.

Contralateral far-lateral approach for clipping of a ruptured vertebral artery-posterior inferior cerebellar artery aneurysm.

Numerous nuanced approaches have been used to access posterior inferior cerebellar artery (PICA) aneurysms for microsurgical clipping. The authors report the case of a patient with a right vertebral artery (VA)-PICA aneurysm that was reached via a contralateral far-lateral approach. The wide-necked saccular/fusiform aneurysm arose from the lateral aspect of the right V(4) segment just proximal to the PICA origin, anterior to the jugular tubercle at the level of the hypoglossal canal. Computed tomography angiograms demonstrated the size and configuration of the aneurysm, and 3D reconstructions revealed the tortuosity of the right VA, defining its location just left of the midline adjacent to the lower clivus. A contralateral far-lateral approach to VA-PICA aneurysms should be considered when aneurysms cross the midline. Computed tomography angiography with volume rendering and interactive software capabilities can help identify the relationship of such an aneurysm to an individual's particular skull base osseous anatomy and is paramount in selecting the optimal microsurgical approach.

Thirty-year follow-up after extracranial-intracranial bypass surgery.

The conventional wisdom resulting from the international, multicenter, trial of extracranial-intracranial bypass surgery is that this procedure offers no benefit. Because of the complex and unique circumstances of some, clinical experience and judgment must sometimes overrule some statistical conclusions.

Double-Barrel Superficial Temporal Artery-Middle Cerebral Artery Bypass: Can It Be Considered "High-Flow?"

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.

Advanced cone-beam CT venous angiographic imaging.

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.