Meteorin Alleviates Paclitaxel-Induced Peripheral Neuropathic Pain in Mice.

Chemotherapy-induced peripheral neuropathy is a challenging condition to treat, and arises due to severe, dose-limiting toxicity of chemotherapeutic drugs such as paclitaxel. This often results in debilitating sensory and motor deficits that are not effectively prevented or alleviated by existing therapeutic interventions. Recent studies have demonstrated the therapeutic effects of Meteorin, a neurotrophic factor, in reversing neuropathic pain in rodent models of peripheral nerve injury induced by physical trauma. Here, we sought to investigate the potential antinociceptive effects of recombinant mouse Meteorin (rmMeteorin) using a paclitaxel-induced peripheral neuropathy model in male and female mice. Paclitaxel treatment (4 × 4 mg/kg, i.p.) induced hind paw mechanical hypersensitivity by day 8 after treatment. Thereafter, in a reversal dosing paradigm, five repeated injections of rmMeteorin (.5 and 1.8 mg/kg s.c. respectively) administered over 9 days produced a significant and long-lasting attenuation of mechanical hypersensitivity in both sexes. Additionally, administration of rmMeteorin ( .5 and 1.8 mg/kg), initiated before and during paclitaxel treatment (prevention dosing paradigm), reduced the establishment of hind paw mechanical hypersensitivity. Repeated systemic administration of rmMeteorin in both dosing paradigms decreased histochemical signs of satellite glial cell reactivity as measured by glutamine synthetase and connexin 43 protein expression in the dorsal root ganglion. Additionally, in the prevention administration paradigm rmMeteorin had a protective effect against paclitaxel-induced loss of intraepidermal nerve fibers. Our findings indicate that rmMeteorin has a robust and sustained antinociceptive effect in the paclitaxel-induced peripheral neuropathy model and the development of recombinant human Meteorin could be a novel and effective therapeutic for chemotherapy-induced peripheral neuropathy treatment. PERSPECTIVE: Chemotherapy neuropathy is a major clinical problem that decreases quality of life for cancer patients and survivors. Our experiments demonstrate that Meteorin treatment alleviates pain-related behaviors, and signs of neurotoxicity in a mouse model of paclitaxel neuropathy.

Lazic Aneurysm Clip System for Microsurgical Clipping of Cerebral Aneurysms: Transition to a New Aneurysm Clip System in an Established Cerebrovascular Practice.

BACKGROUND: In an era of continued advancements in endovascular treatment of cerebral aneurysms, novel developments concerning microsurgical clipping are sparse. The Lazic aneurysm clip system represents such an advancement. The applier has a malleable shaft and is designed to minimally obstruct the view of the surgical field. The purpose of this study was to illustrate the transition to this new aneurysm clip system in an established cerebrovascular practice. METHODS: We retrospectively reviewed all aneurysms treated with microsurgical clipping using the Lazic aneurysm clip system in 1 cerebrovascular practice in the United States from January 2009 to June 2016. RESULTS: Between 2009 and 2016, a total of 973 aneurysms underwent surgical clipping. The Lazic clip system was used in 191 (19.6%) aneurysms (maximum diameter, 5.6 ± 3.8 mm) in 181 patients. The middle cerebral artery was the most frequent location (25.7%) followed by posterior communicating artery (20.9%). There was a continuous increase in the percentage of aneurysms treated with the Lazic clip system from 6% in 2009 to 98% in 2016. The proportion of posterior circulation aneurysms treated with Lazic clips decreased, whereas the middle cerebral artery location increased. There were a total of 11 complications (5.8%), but no instances of clip malfunction. CONCLUSIONS: In the largest series to date, the Lazic clip system proved to be safe and efficacious and presents an interesting alternative to established aneurysm clip systems. This study illustrates the transition of an established cerebrovascular practice to the Lazic clip system.

Response of silent corticotroph pituitary carcinoma to chemotherapy: case report.

Silent pituitary corticotroph carcinomas are rare, with only six previously described cases in the literature. We report a patient with a silent pituitary corticotroph adenoma treated with multiple trans-sphenoidal resections. Twelve years after her initial presentation, she returned with leptomeningeal metastases to the posterior fossa, foramen magnum, and numerous other subarachnoid locations involving the spine. Histopathology obtained from the metastatic foci was identical to previous trans-sphenoidal specimens - consistent with the diagnosis of corticotroph pituitary carcinoma. A carboplatin and etoposide chemotherapy regimen successfully arrested disease progression and produced regression of multiple radiographically documented leptomeningeal deposits. To the authors' knowledge, this is the first report of a patient with silent pituitary carcinoma treated successfully with chemotherapy.

Aberrant cervical vasculature anastomosis as cause of neck pain and successful treatment with embolization technique.

We report a patient with non-dermatomal radiating neck pain without focal neurologic deficit. Traditional workup could not identify an anatomic or biomechanical cause. Imaging showed a deep cervical vessel centered in the region of pain. Angiography later identified an aberrant anastomosis of this vessel with the occipital artery. Subsequent endovascular embolization of this arterial trunk resulted in complete pain relief.

Rule of 5: angiographic diameters of cervicocerebral arteries in children and compatibility with adult neurointerventional devices.

BACKGROUND AND PURPOSE: The safety of using adult-sized neuroendovascular devices in the smaller pediatric vasculature is not known. In this study we measure vessel diameters in the cervical and cranial circulation in children to characterize when adult-approved devices might be compatible in children. METHODS: For 54 children without vasculopathy (mean age 9.5±4.9 years (range 0.02-17.8), 20F/34M) undergoing catheter angiography, the diameters of the large vessels in the cervical and cranial circulation (10 locations, 611 total measurements) were assessed by three radiologists. Mean±SD diameter was calculated for the following age groups: 0-6 months, 1, 2, 3, 4, 5-9, 10-14, and 15-18 years. To compare with adult sizes, each vessel measurement was normalized to the respective region mean diameter in the oldest age group (15-18 years). Normalized measurements were compared with age and fitted to a segmented regression. RESULTS: Vessel diameters increased rapidly from 0 to 5 years of age (slope=0.069/year) but changed minimally beyond that (slope=0.005/year) (R(2)=0.2). The regression model calculated that, at 5 years of age, vessels would be 94% of the diameter of the oldest age group (compared with 59% at birth). In addition, most vessels in children under 5, while smaller, were still potentially large enough to be compatible with many adult devices. CONCLUSIONS: The growth curve of the cervicocerebral vasculature displays rapid growth until age 5, at which point most children's vessels are nearly adult size. By age 5, most neuroendovascular devices are size-compatible, including thrombectomy devices for stroke. Under 5 years of age, some devices might still be compatible.

Minimizing bleeding complications in spinal tumor surgery with preoperative Onyx embolization via dual-lumen balloon catheter.

BACKGROUND: Intraoperative bleeding is a significant risk in surgery for highly vascular spinal tumors, but preoperative embolization can safely decrease intraoperative blood loss in extrinsic spine tumors. Onyx, widely used for cerebrovascular embolization, has been increasingly used as an embolic agent for preoperative spinal tumor embolization. The Scepter catheter, a dual-lumen balloon catheter, may improve tumor parenchymal penetration without the danger and limitations of significant embolic reflux. This may reduce bleeding risk during spinal surgery. METHODS: Eleven consecutive cases of preoperative Onyx embolization of extrinsic spinal tumors were identified, all of whom had subsequent spinal surgery. Demographic data and clinical variables were collected. Patients were divided into Scepter (n=6) and non-Scepter (n=5) groups. The Mann-Whitney U test was used to compare continuous outcome variables and the Fisher exact test was used to compare categorical variables. RESULTS: Estimated blood loss in the Scepter group was significantly lower than in the non-Scepter group (584±124 vs 2400±738 mL, p=0.004). The volume of intraoperative transfusion was also significantly lower (1.2±0.4 vs 5.8±1.7 units, p=0.004). There was no significant difference in the number of vessels embolized, vials of Onyx used, use of coiling adjunct, contrast load, radiation dose, or fluoroscopy time per pedicle (p>0.05). CONCLUSIONS: The addition of the Scepter catheter to preoperative Onyx embolization is safe and feasible. In this small series, the Scepter catheter was associated with a reduction of intraoperative bleeding by 76% and a 79% lower transfusion volume. This was not accompanied by any unwanted increase in vials of Onyx used, contrast load, radiation dose, or fluoroscopy time.

Simultaneous stent expansion/balloon deflation technique to salvage failed balloon remodeling.

Herniation, with possible embolization, of coils into the parent vessel following aneurysm coiling remains a frequent challenge. For this reason, balloon or stent assisted embolization remains an important technique. Despite the use of balloon remodeling, there are occasions where, on deflation of the balloon, some coils, or even the entire coil mass, may migrate. We report the successful use of a simultaneous adjacent stent deployment bailout technique in order to salvage coil prolapse during balloon remodeling in three patients. Case No 1 was a wide neck left internal carotid artery bifurcation aneurysm, measuring 9 mm×7.9 mm×6 mm with a 5 mm neck. Case No 2 was a complex left superior hypophyseal artery aneurysm, measuring 5.3 mm×4 mm×5 mm with a 2.9 mm neck. Case No 3 was a ruptured right posterior communicating artery aneurysm, measuring 4 mm×4 mm×4.5 mm with a 4 mm neck. This technique successfully returned the prolapsed coil mass into the aneurysm sac in all cases without procedural complications. The closed cell design of the Enterprise VRD (Codman and Shurtleff Inc, Raynham, Massachusetts, USA) makes it ideal for this bailout technique, by allowing the use of an 0.021 inch delivery catheter (necessary for simultaneous access) and by avoiding the possibility of an open cell strut getting caught on the deflated balloon. We hope this technique will prove useful to readers who may find themselves in a similar predicament.

Initial experience with dual-lumen balloon catheter injection for preoperative Onyx embolization of skull base paragangliomas.

OBJECT Paragangliomas are highly vascular head and neck tumors for which preoperative embolization is often considered to facilitate resection. The authors evaluated their initial experience using a dual-lumen balloon to facilitate preoperative embolization in 5 consecutive patients who underwent preoperative transarterial Onyx embolization assisted by the Scepter dual-lumen balloon catheter between 2012 and 2014. OBJECT The authors reviewed the demographic and clinical records of 5 patients who underwent Scepter-assisted Onyx embolization of a paraganglioma followed by resection between 2012 and 2014. Descriptive statistics of clinical outcomes were assessed. RESULTS Five patients (4 with a jugular and 1 with a vagal paraganglioma) were identified. Three paragangliomas were embolized in a single session, and each of the other 2 were completed in 3 staged sessions. The mean volume of Onyx used was 14.3 ml (range 6-30 ml). Twenty-seven vessels were selectively catheterized for embolization. All patients required selective embolization via multiple vessels. Two patients required sacrifice of parent vessels (1 petrocavernous internal carotid artery and 1 vertebral artery) after successful balloon test occlusion. One patient underwent embolization with Onyx-18 alone, 2 with Onyx-34 alone, and 1 with Onyx-18 and -34. In each case, migration of Onyx was achieved within the tumor parenchyma. The mean time between embolization and resection was 3.8 days (range 1-8 days). Gross-total resection was achieved in 3 (60%) patients, and the other 2 patients had minimal residual tumor. The mean estimated blood loss during the resections was 556 ml (range 200-850 ml). The mean postoperative hematocrit level change was -17.3%. Two patients required blood transfusions. One patient, who underwent extensive tumor penetration with Onyx, developed a temporary partial cranial nerve VII palsy that resolved to House-Brackmann Grade I (out of VI) at the 6-month follow-up. One patient experienced improvement in existing facial nerve weakness after embolization. CONCLUSIONS Scepter catheter-based Onyx embolization seems to be safe and effective. It was associated with excellent distal tumor vasculature penetration and holds promise as an adjunct to conventional transarterial Onyx embolization of paragangliomas. However, the ease of tumor penetration should encourage caution in practitioners who may be able to effect comparable improvement in blood loss with more conservative proximal Onyx penetration.

TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration.

Agents that promote tissue regeneration could be beneficial in a variety of clinical settings, such as stimulating recovery of the hematopoietic system after bone marrow transplantation. Prostaglandin PGE2, a lipid signaling molecule that supports expansion of several types of tissue stem cells, is a candidate therapeutic target for promoting tissue regeneration in vivo. Here, we show that inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme, potentiates tissue regeneration in multiple organs in mice. In a chemical screen, we identify a small-molecule inhibitor of 15-PGDH (SW033291) that increases prostaglandin PGE2 levels in bone marrow and other tissues. SW033291 accelerates hematopoietic recovery in mice receiving a bone marrow transplant. The same compound also promotes tissue regeneration in mouse models of colon and liver injury. Tissues from 15-PGDH knockout mice demonstrate similar increased regenerative capacity. Thus, 15-PGDH inhibition may be a valuable therapeutic strategy for tissue regeneration in diverse clinical contexts.

Transorbital superior ophthalmic vein sacrifice to preserve vision in ocular hypertension from aseptic cavernous sinus thrombosis.

Aseptic cavernous sinus thrombosis (CST) is rare and may clinically masquerade as a carotid cavernous fistula. Conventional management includes oral anticoagulation, but cases of ocular hypertension affecting vision may require more aggressive intervention. We report a case of a woman with spontaneous bilaterally occluded cavernous sinuses with elevated intraocular pressure (IOP), which resolved immediately following unilateral superior ophthalmic vein (SOV) sacrifice. She was subsequently placed on oral anticoagulants. By 4 months postoperatively her IOP was normalized and her vision had improved. Repeat angiography demonstrated stable venous filling, with some mild improvement of flow through the cavernous sinus. Coil-mediated sacrifice of the SOV might be an effective means to relieve ocular hypertension and preserve vision in the setting of aseptic CST.

Complex decision-making in stroke: preoperative mechanical thrombectomy of septic embolus for emergency cardiac valve surgery.

Stroke is a common and devastating embolic manifestation of infective endocarditis. We report a case of cardioembolic stroke in a patient with enterococcal endocarditis, with National Institutes of Health Stroke Scale score of 3. A middle-aged patient with bacterial endocarditis exhibited mild intermittent left hemiparesis and dysarthria in the setting of severe aortic insufficiency requiring urgent aortic valve replacement. Cerebrovascular imaging revealed a partially occlusive thrombus in the M1 segment of the right middle cerebral artery, which became symptomatic during relative hypotension. Given the expected hypotension during the urgently needed aortic valve replacement, there was a significant risk of infarction of most of the right hemisphere. Thus, mechanical thrombectomy was performed immediately prior to thoracotomy, and the patient awoke neurologically intact. This case demonstrates avoidance of a large stroke due to a subocclusive thrombus and anticipated intraoperative hypotension with preoperative mechanical thrombectomy.

Mechanical thrombectomy for acute stroke in childhood: how much does restricted diffusion matter?

Mechanical thrombectomy holds promise for children with large cerebral arterial occlusions, although there are few reports in this population. We report a case of retrievable stent-assisted mechanical thrombectomy in a 5-year-old with basilar artery occlusion, despite late presentation and extensive initial diffusion-weighted imaging (DWI) restriction. This resulted in successful Thrombolysis in Cerebral Infarction 2B reperfusion and excellent clinical outcome. At 6-week follow-up he was completely back to baseline with no residual deficits (pediatric stroke outcome measure=0, modified Rankin scale=0). At 3-month follow-up the patient has not had any recurrent stroke or concern for stroke-like symptoms. We review the literature on mechanical thrombectomy and DWI changes in acute stroke in early to middle childhood (<12 years old).

Complex decision-making in stroke: preoperative mechanical thrombectomy of septic embolus for emergency cardiac valve surgery.

Stroke is a common and devastating embolic manifestation of infective endocarditis. We report a case of cardioembolic stroke in a patient with enterococcal endocarditis, with National Institutes of Health Stroke Scale score of 3. A middle-aged patient with bacterial endocarditis exhibited mild intermittent left hemiparesis and dysarthria in the setting of severe aortic insufficiency requiring urgent aortic valve replacement. Cerebrovascular imaging revealed a partially occlusive thrombus in the M1 segment of the right middle cerebral artery, which became symptomatic during relative hypotension. Given the expected hypotension during the urgently needed aortic valve replacement, there was a significant risk of infarction of most of the right hemisphere. Thus, mechanical thrombectomy was performed immediately prior to thoracotomy, and the patient awoke neurologically intact. This case demonstrates avoidance of a large stroke due to a subocclusive thrombus and anticipated intraoperative hypotension with preoperative mechanical thrombectomy.