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.
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.
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.
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.
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.
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.
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.
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).
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.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
BACKGROUND:Ventriculoperitoneal shunting is one of the most commonly performed neurosurgical procedures. Typically, for insertion of the peritoneal catheter, a mini-laparotomy technique is used. ...Although generally safe, it can be cosmetically undesirable and time consuming. Complications include malpositioning, bowel injury, and delayed hernias. Laparoscopic techniques have been advocated to address these issues, but have been slow to gain traction with neurosurgeons.
OBJECTIVE:To describe our experience with single port optical access laparoscopy for placement of ventriculoperitoneal shunts. Our technique simplifies adoption of a laparoscopic technique for neurosurgeons looking to incorporate its benefits.
METHODS:All ventriculoperitoneal shunts placed by the senior author since April 2011 were retrospectively reviewed. Surgical and perioperative complications, length of postoperative stay, and need for revisions were analyzed.
RESULTS:Fifty-six patients were included in the study. There were no cases of peritoneal catheter misplacement. One intraoperative complication occurred early in the series, in which there was an injury to the gallbladder necessitating cholecystectomy. There were 7 cases followed by shunt revision inclusive of the abdomen. In 3 cases, pseudocysts were noted.
CONCLUSION:Single port optical access laparoscopy is a fast and minimally invasive technique that allows direct visualization of the layers of the abdominal wall as they are traversed and visualization of the peritoneal catheter during placement. It uses a small cosmetic incision and obviates the need for postoperative abdominal radiographic studies. The procedure has a modest learning curve, but can be safely used without the assistance of an assist surgeon after the skills are acquired.
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.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Attacks of hereditary angioedema are attributed to excessive plasma kallikrein (PKa) activity, which cleaves high-molecular-weight kininogen to generate the proinflammatory hormone bradykinin.
We ...evaluated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of KVD900, an orally administered inhibitor of PKa in healthy adults.
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.
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.
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.
NCT04349800
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
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.
FXIIa inhibitors designed to target its catalytic domain also potently inhibited the enzymatic activity of rFXII-T and the pIC
s of these compounds linearly correlated for rFXIIa and rFXII-T (
= 0.93). KV998086, a potent oral FXIIa inhibitor (IC
= 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 (
< 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.
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.
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