Management of brain AVM procedural hemorrhagic complication by the "security" catheter technique.

Since the introduction of Onyx as a liquid embolic agent for the treatment of brain arteriovenous malformation (AVM), higher endovascular cure rates have been achieved. This may be partially attributed to its non-adhesive property, which allows longer intranidal progression of the embolic agent before solidification. However, Onyx reflux around the microcatheter can form a highly viscous plug, thereby constraining the microcatheter during its retrieval. Also, during the maneuver, arterial stretching can lead to vascular rupture and result in acute bleeding, a potentially fatal complication that demands immediate treatment. This report describes a new treatment strategy for the rapid management of such a complication. The technique consists of the placement of a second microcatheter about 2 cm proximal to the AVM nidus in the same artery containing the intranidal microcatheter. After conclusion of embolization, if rupture occurs during intranidal microcatheter retrieval, the second microcatheter that is already in place can promptly be used to control the bleeding.

Radiosurgery for large cerebral arteriovenous malformations.

BACKGROUND: Radiosurgery is an effective treatment option for patients with small to medium sized arteriovenous malformations. However, it is not generally accepted as an effective tool for larger (>14 cm(3)) arteriovenous malformations because of low obliteration rates. The authors assessed the applicability and effectiveness of radiosurgery for large arteriovenous malformations. METHOD: We performed a retrospective study of 46 consecutive patients with more than 14 ml of arteriovenous malformations who were treated with radiosurgery using a linear accelerator and gamma knife (GK). They were grouped according to their initial clinical presentation-17 presented with and 29 without haemorrhage. To assess the effect of embolization, these 46 patients were also regrouped into two subgroups-25 with and 21 without preradiosurgical embolization. Arteriovenous malformations found to have been incompletely obliterated after 3-year follow-up neuroimaging studies were re-treated using a GK. FINDINGS: The mean treatment volume was 29.5 ml (range, 14.0-65.0) and the mean marginal dose was 14.1 Gy (range, 10.0-20.0). The mean clinical follow-up periods after initial radiosurgery was 78.1 months (range, 34.0-166.4). Depending on the results of the angiography, 11 of 33 patients after the first radiosurgery and three of four patients after the second radiosurgery showed complete obliteration. Twenty patients received the second radiosurgery and their mean volume was significantly smaller than their initial volume (P = 0.017). The annual haemorrhage rate after radiosurgery was 2.9% in the haemorrhage group (mean follow-up 73.3 months) and 3.1% in the nonhaemorrhage group (mean follow-up 66.5 months) (P = 0.941). Preradiosurgical embolization increased the risk of haemorrhage for the nonhaemorrhage group (HR, 28.03; 95% CI, 1.08-6,759.64; P = 0.039), whereas it had no effect on the haemorrhage group. Latency period haemorrhage occurred in eight patients in the embolization group, but in no patient in the nonembolization group (P = 0.004). CONCLUSIONS: Radiosurgery may be a safe and effective arteriovenous malformation treatment method that is worth considering as an alternative treatment option for a large arteriovenous malformation.

Brain aneurysms and arteriovenous malformations: advancements and emerging treatments in endovascular embolization.

BACKGROUND AND PURPOSE: Brain aneurysms and vascular malformations can cause cerebral hemorrhages, with devastating consequences for the patients and their families. Since the development of microcatheters and materials used for endovascular embolization, we have witnessed a rapid advancement in the technology and in the number or patients treated with this approach. The aim of this review is to survey recent data relevant to new technologies and emerging treatment strategies in these areas. SUMMARY OF REVIEW: Clinical trials assessing the safety and efficacy of coil embolization for cerebral aneurysms were based on the use of bare platinum, helical coils. Since then, endovascular operators have been testing and using new materials such as bioactive coils, expandable coils, and complex-shaped coils. Based on the data so far obtained, third and fourth generation coil designs are rapidly emerging and will be ready for clinical application in the near future. Balloon- and stent-assisted coil embolization is enabling the treatment of complex, large-neck aneurysms and the vascular reconstruction of lesions previously considered not treatable. New open- and closed-cell designs allow the navigation and deployment of stents in extremely tortuous vessels. With regards to the embolization of vascular malformations, it is possible to safely navigate microcatheters and microwires through very small arteries previously considered not accessible. In addition, embolization materials such as n-butyl cyanoacrylate and ethylene-vinyl alcohol copolymer are now routinely injected to safely reduce or obliterate large and complex arteriovenous malformations and fistulae. CONCLUSIONS: Advancements in technology are rapidly improving the endovascular approach to the treatment of cerebral aneurysms and arteriovenous malformations.

Onyx: a unique neuroembolic agent.

Rupture of a cerebral arteriovenous malformation can result in devastating hemorrhage with a possibility of serious neurological injury or death. Endovascular embolization is an important adjunct in the treatment of cerebral arteriovenous malformations, and in a small number of cases may provide definitive treatment. Currently available embolic agents have several shortcomings, including the possibility of recanalization, adhesiveness to the endovascular microcatheter and suboptimal handling at the time of surgical resection. Onyx is an ethylene vinyl alcohol copolymer dissolved in dimethyl sulfoxide that was approved by the US FDA in July 2005 as an embolic agent for brain arteriovenous malformations. Although long-term follow-up is limited, this agent appears to offer several advantages over the other available embolic agents for the endovascular management of arteriovenous malformations and other vascular lesions.

The practical management of haemophilia.

Haemophilia is a rare and complex disorder and its successful management will depend upon the establishment of a network of 'comprehensive care' including the services of haematologists, orthopaedic surgeons, rheumatologists, dental surgeons, physiotherapists, specialised nurses and counsellors. One of the major lessons to be learned from the HIV epidemic in haemophilia is that it is critical to strive to obtain the safest and purest forms of blood products for these patients. The advent of clinically available recombinant factor VIII is expected soon; in the meantime there is a move towards treating all patients with high purity products.

Hemostatic agents: brain tissue reaction and effectiveness. A comparative animal study using collagen fleece and oxidized cellulose.

In a series of 26 young rabbits, three cortical lesions were made in each hemisphere. Two of these holes were filled with collagen fleece (CF) and oxidized cellulose (OC), respectively, while the third was left empty as a control. The bleeding time was measured. Hemostasis with CF was statistically significantly faster than with OC, which in turn was statistically significantly faster than with no hemostatic agent. The animals were killed successively on Days 7, 14, 28, 42, and 241 after operation. Histopathological investigation showed that CF did not induce more tissue reaction that the control lesion and that CF was resorbed faster than OC. The removal of OC occurred from the borders of the material, moving gradually inward. With CF, there was an immediate ingrowth of reactive cells throughout the material. In contrast to OC, CF did not induce the formation of polynucleated giant cells. From these results, it can be concluded that CF is a fast, safe, and absorbable topical hemostatic agent suitable for use in neurosurgical procedures.

Hemorrhagic complications during extracorporeal membrane oxygenation: prevention and treatment.

Hemorrhage related to systemic heparinization is the major complication of extracorporeal membrane oxygenation (ECMO). Intracranial hemorrhage (ICH) is the most devastating complication. ICH developed in 13 of our 25 ECMO patients (52%). Six died, six survived with normal neurologic function, and one is severely impaired. In nine of 13 patients (69%) ECMO was discontinued when serial cranial ultrasounds showed progressive ICH. Seizures developed in six infants while receiving ECMO, and ICH developed in all. There is a correlation between hypertension and ICH. A hypertension index (hours systolic BP greater than 90/hours receiving ECMO) was 0.1 +/- 0.12 for infants without ICH and 0.37 +/- 0.28 for infants with ICH (P less than .05). ICH developed in 79% of the patients with an index greater than 0.1. Twenty neck explorations were required in the first 20 patients for incisional bleeding (mean blood loss, 21.9 +/- 18.0 mL/kg/d). We now use fibrin glue following cannulation and have done only one neck exploration in the last five patients (mean blood loss, 2.8 +/- 2.2 mL/kg/d, P less than .05). Endobronchial bleeding has responded to phenylephrine lavage and increased positive end-expiratory pressure. We have controlled pleural space bleeding with topical thrombin. None of the hemorrhagic complications encountered correlate with the activated clotting time or the amount of heparin used. There is an increased risk of hemorrhage associated with platelet counts less than 100,000/microL for 75% of a day (P less than .05) so that aggressive platelet transfusion remains important in preventing hemorrhagic complications during ECMO.

Neurosurgical applications of the cyanoacrylate adhesives.

The cyanoacrylate adhesives are a biologically heterogenous group, some of which are potentially valuable additions to the neurosurgical armamentarium. The commercially available cyanoacrylates usually contain the more toxic methyl and ethyl monomers. The safe butyl monomer, isobutyl 2-cyanoacrylate, is approved in the United States by the Food and Drug Administration for investigational use only. Isobutyl 2-cyanoacrylate may prove to be useful for the extravascular reinforcement of intracranial aneurysms and for the intravascular occlusion of carotid-cavernous fistulae. Safe and effective alternatives exist for the management of these two problems. The sealing of certain cerebrospinal fluid fistulae and the intravascular occlusion of certain arteriovenous malformations may be more effectively accomplished with isobutyl 2-cyanoacrylate than with other currently available techniques. The ultimate role of this and of other as yet untested cyanoacrylates in neurosurgery remains to be determined.

Predictors of hemorrhagic complications from endovascular treatment of cerebral arteriovenous malformations.

Post-embolization hemorrhage is the most severe, dramatic and morbidity-mortality-related complication in the treatment of endovascular arteriovenous malformations (AVMs). The objective of this study was to determine predictive factors of post-embolization hemorrhage. This is a retrospective study in 71 patients with cerebral AVMs having undergone 147 embolization sessions with n-butyl cyanoacrylate (n-BCA), carried out between 2006 and 2011. Clinical-demographic, morphological and treatment data as well as results were recorded. The relationship of post-procedure hemorrhage with demographic and morphological factors, percentage devascularization per session, venous drainage and whether or not post-procedure hypotension had been induced was investigated. Six post-embolization hemorrhages occurred, all in sessions characterized by extensive devascularization without the induction of post-procedure hypotension; which disappeared after a limit to the extent of devascularization per session and post-procedure hypotension were introduced. In the multivariate analysis, hemorrhage predictors were: nidus diameter < 3 cm (OR= 45.02; CI=95%:1.17-203.79; P=0.005); devascularization > 40% (OR=32.4; CI=95%: 3.142- 518.6; P=0.009) per session; intranidal aneurysms (OR=7.5; CI=95%:1.19-341.3; P=0.041) and lack of post-procedure hypotension (OR=16.51; CI=95%:1.81-324.4; P=0.049) and the association of sessions with devascularization exceeding 40% with lack of post-procedure hypotension, showed an increase in the risk of hemorrhage (OR=36.4; CI=95%:3.67-362.4; P=0.002). Extensive devascularization and the absence of post-procedure hypotension increase the risk of hemorrhage. We suggest partial, 25-30%, devascularization per session and the induction of post-procedure hypotension, which produces a 20% decrease of the basal mean arterial pressure (MAP).

Nanosuspension development of scutellarein as an active and rapid orally absorbed precursor of its BCS class IV glycoside scutellarin.

This work addressed solubility and membrane permeability problems of Biopharmaceutics Classification System (BCS) Class IV glycoside scutellarin (SG) by developing a nanosuspension of its aglycone scutellarein (S) as a precursor. An S nanosuspension containing poloxamer 188 was prepared using antisolvent precipitation where hydroxypropyl-ß-cyclodextrin was utilized as a lyophilizing protectant. Particle size and polydispersity index after redispersion were 342.6 ± 18.2 and 0.32 ± 0.06 nm, respectively. The dissolution rate of the S nanosuspension was superior compared with the physical mixture. No free S, but SG and SG's isomer were detected in plasma following oral delivery of SG or S, S nanosuspension or physical mixture of S. The Cmax values of SG after dosing with the S nanosuspension were 12.0, 8.0, and 4.5-fold higher than the SG, S, or physical mixture, respectively. The Tmax and mean residence time (MRTlast ) of SG after dosing with the S nanosuspension were significantly shorter than S and SG. Treatments with SG, S, or S nanosuspensions reduced the hemorrhage rate in a zebrafish model, but the S nanosuspension exhibited the strongest rescue effect. This study highlights a new strategy to circumvent BCS Class IV flavonoid glycosides using a formulation of their aglycone as a precursor to accelerate oral absorption and improve bioactivity.

Embolization of meningiomas: comparison of safety between calibrated microspheres and polyvinyl-alcohol particles as embolic agents.

BACKGROUND AND PURPOSE: During embolization of meningiomas, intratumoral hemorrhagic complications may occur, especially with the use of small particle sizes. We compared the rate of hemorrhagic complications in 55 patients embolized with 400-µm calibrated microspheres (Embozene) with a historical cohort of 198 patients embolized with smaller PVA particles. MATERIALS AND METHODS: Between September 2009 and February 2012, fifty-five patients with 55 meningiomas were embolized with 400-µm calibrated microspheres. Indications for embolization were preoperative in 47 and before radiosurgery in 2 patients; and in 6 patients, embolization was offered as sole therapy. There were 35 women and 20 men with a mean age of 60.3 years. Mean meningioma diameter was 53 mm (range, 23-97 mm). Hemorrhagic complications were recorded. RESULTS: There were no hemorrhagic complications in the 55 embolized patients (0%; 95% CI, 0.0%-7.8%). The difference in complication rates between 400-µm calibrated microspheres in this study (0 of 55, 0%) and small PVA particles (45-150 µm) in the historical cohort (9 of 108, 8.3%) was just short of significance (P=.066). The difference in complication rates between 400-µm calibrated microspheres (0 of 55, 0%) and larger PVA particles (150-250 µm) in the historical cohort (1 of 93, 1.1%) was not significant (P=.8). CONCLUSIONS: In this series, embolization of meningiomas by using large (400-µm) calibrated microspheres did not result in any hemorrhagic complications.

Endovascular treatment of deep hemorrhagic brain arteriovenous malformations with transvenous onyx embolization.

SUMMARY: Brain AVMs are a rare cause of cerebral hemorrhage and SAH, and their treatment is still debated. The aim of this study was to describe a novel endovascular approach with transvenous embolization of deep hemorrhagic brain AVMs. Five patients (3 females, 2 males; mean age, 33.2 years) underwent a transvenous embolization of a deep hemorrhagic brain AVM at our institution between February and April 2012. Clinical and angiographic data at the end of the procedure and after 6 months are reported. All the AVMs were completely obliterated, and no intra- or postprocedural complications occurred. The clinical outcome was unchanged or improved in all patients. Transvenous endovascular treatment may be considered in small, hemorrhagic, and deep AVMs with single deep drainage in those cases in which neurosurgical and radiosurgical treatment might not be indicated.

Endovascular treatment of ruptured brain AVMs in the acute phase of hemorrhage.

BACKGROUND AND PURPOSE: Patients with ruptured brain AVMs are at considerable risk of repeat hemorrhage, particularly when associated intranidal or flow-related aneurysms are present. There is controversy about the timing of diagnosis and treatment of patients with hemorrhagic stroke. We present our results of endovascular treatment of ruptured AVMs in the acute phase. MATERIALS AND METHODS: Between January 2008 and March 2011, 23 patients (16 men, 7 women; mean age 42 years) with AVM-related hemorrhagic stroke were treated with endovascular techniques within 10 days of the ictus. There were 10 micro-AVMs (< 1 cm) and 1 single-hole pial fistula. In 9 patients, an intranidal or flow-related aneurysm was the likely cause of hemorrhage. RESULTS: Complete obliteration of the AVM with Onyx was achieved in 13 of 23 patients (57%). Eight of the 13 AVMs were micro-AVMs and 3 had an intranidal aneurysm. Partial obliteration of the AVM was achieved in 10 of 23 patients (43%). In 6 of these 10 patients, an intranidal (n = 1) or flow-related aneurysm (n = 5) was obliterated with Onyx or coils. There were no complications of treatment. During a mean follow-up of 21 months in 22 surviving patients, no repeat hemorrhage occurred. CONCLUSIONS: Endovascular treatment with Onyx in the acute phase cured most ruptured AVMs. All 9 AVM-associated aneurysms that were considered the source of hemorrhage could be excluded from the circulation. In patients with AVM-related hemorrhagic stroke, prompt angiographic diagnosis and treatment may improve prognosis by reducing repeat hemorrhage rate.

Transarterial treatment with Onyx of intracranial dural arteriovenous fistula with cortical drainage in 17 patients.

BACKGROUND AND PURPOSE: Intracranial DAVFs with cortical venous drainage have a high tendency to bleed. Complete closure of these lesions is essential to prevent clinically deleterious events. We describe our experience using Onyx in an arterial approach for treatment of DAVFs in 17 patients. MATERIALS AND METHODS: Between 2006 and 2010, we used Onyx for performing transarterial embolization in 17 patients with intracranial DAVFs and cortical venous drainage. Clinical assessment was performed before and after every treatment at discharge and at follow-up. Fourteen patients underwent follow-up MR imaging and MRA, 8 of them also underwent follow-up diagnostic angiography. RESULTS: Fifteen patients (88%) underwent 1 procedure. Complete obliteration by embolization with Onyx was achieved in 16 patients (94% acute obliteration). The mean amount of Onyx injected was 2.3 mL (range, 0.4-4.8 mL). The sole technical complication was an embolus to a branch of the MCA, which was resolved by intra-arterial tPA injection. A clinical complication of transient trochlear nerve palsy in the same patient due to mass effect of Onyx resolved spontaneously within 3 months. CONCLUSIONS: Intra-arterial embolization of cranial DAVFs with cortical venous drainage by using Onyx results in a high rate of complete obliteration (94%) with low morbidity (6%). Follow-up DSA in 8 patients revealed no evidence of reopening.

Endovascular treatment of intracranial arteriovenous malformation.

Arteriovenous malformations (AVMs) of the brain are vascular lesions in which an abnormal tangle or nidus of vessels permits pathologic shunting of blood flow from the arterial to the venous tree without an intervening capillary bed. With brain imaging techniques, an increasing number of AVMs are detected before they hemorrhage, leading to new considerations and modifications of interdisciplinary management strategies. Treatment options include endovascular embolization, microsurgical resection, radiosurgery, medical management, or a combination of these. Neuroendovascular therapy is a critical component of this multidisciplinary and multimodal approach. The development and introduction of newer techniques and agents will continue to affect embolization treatments.

Endovascular treatment of intracranial dural arteriovenous fistulas with cortical venous drainage: new management using Onyx.

BACKGROUND AND PURPOSE: DAVFs (dural arteriovenous fistulas) represent one of the most dangerous types of intracranial AV shunts. Most of them are cured by arterial or venous embolization, but surgery/radiosurgery can be required in case of failure. Our goal was to reconsider the endovascular treatment strategy according to the new possibilities of arterial embolization using non polymerizing liquid embolic agent. MATERIALS AND METHODS: Thirty patients were included in a prospective study during the interval between July 2003 and November 2006. Ten of these had type II, 8 had type III, and 12 had type IV fistulas. Sixteen presented with hemorrhage. Five had been treated previously with other embolic materials. RESULTS: Complete angiographic cure was obtained in 24 cases. Of these 24 cures, 20 were achieved after a single procedure. Cures were achieved in 23 of 25 patients who had not been embolized previously and in only 1 of 5 previously embolized patients. Among these 24 patients, 23 underwent a follow-up angiography, which has confirmed the complete cure. Partial occlusion was obtained in 6 patients, 2 were cured after additional surgery, and 2 underwent radiosurgery. Onyx volume injected per procedure ranged from 0.5 to 12.2 mL (mean, 2.45 mL). Rebleeding occurred in 1 completely cured patient at day 2 due to draining vein thrombosis. One patient had cranial nerve palsy that resolved. Two ethmoidal dural arteriovenous fistulas were occluded. All 10 of the patients with sinus and then CVR drainage were cured. CONCLUSION: Based on this experience, we believe that Onyx may be the treatment of choice for many patients with intracranial dural arteriovenous fistula (ICDAVF) with direct cortical venous reflux (CVR). The applicability of this new embolic agent indicates the need for reconsideration of the global treatment strategy for such fistulas.

[Some methods of prevention and replacement of blood loss during surgical treatment of meningiomas of the brain]. / Nekotorye metody profilaktiki i vospolneniia krovopoteri pri khirurgicheskom lechenii meningiom golovnogo mozga

To control hemodynamic disturbances during removal of cerebral meningiomas a successful application finds a method of preliminary embolism of afferent vessels of the newgrowth alimenting it from the external carotid system with polystyrene emboli and of direct blood transfusion. The preliminary embolism of vessels belonging to the external carotid system and feeding the tumour was effected in 12 patients. In 18 other patients, operated upon in connection with brain meningiomas, 44 direct blood transfusion were practiced. The described measures are helpful in successfully removing at one time large brain meningiomas with good subsequent results.

Controlled trial of a single dose of synthetic surfactant at birth in premature infants weighing 500 to 699 grams. The American Exosurf Neonatal Study Group I.

In a multicenter, double-blind, placebo-controlled trial conducted at 23 hospitals in the United States, a single prophylactic 5 ml/kg dose of a synthetic surfactant (Exosurf Neonatal) or air placebo was administered shortly after birth to 215 infants with birth weights of 500 to 699 gm. Despite stratification at entry by birth weight and gender, by chance female infants predominated in the air placebo group and male infants predominated in the surfactant group. Among infants receiving synthetic surfactant, improvements in oxygen requirements were significant at 2 hours after birth (p = 0.014) and persisted for 3 days (p = 0.001); improvements in the alveolar-arterial partial pressure of oxygen gradient were significant at 6 hours after birth (p = 0.01) and persisted for 3 days (p = 0.008). Improvements in mean airway pressure were not significant at 2 or at 6 hours after birth (p = 0.622 and 0.083, respectively), but became significant thereafter and persisted for 3 days (p = 0.002). Pneumothorax was reduced by slightly more than half (25 vs 11; p = 0.014); death from respiratory distress syndrome (RDS) was also reduced (26 vs 15; p = 0.046). Overall neonatal mortality, however, was not significantly reduced (58 vs 46; p = 0.102). Other complications of RDS and prematurity were not altered, except that pulmonary hemorrhage occurred significantly more frequently in infants receiving synthetic surfactant (2 vs 12; p = 0.006). These findings indicate that a single prophylactic dose of synthetic surfactant in infants weighing 500 to 699 gm at birth improves lung function, incidence of air leak, and death from RDS but not overall mortality. The only safety problem identified was an increase in pulmonary hemorrhage.

A multicenter randomized masked comparison trial of synthetic surfactant versus calf lung surfactant extract in the prevention of neonatal respiratory distress syndrome.

OBJECTIVE: To compare the efficacy and safety of a synthetic surfactant (Exosurf Neonatal, Burroughs Wellcome Co) and a surfactant extract of calf lung lavage (Infasurf, IND #27,169, ONY, Inc) in the prevention of neonatal respiratory distress syndrome (RDS). DESIGN AND SETTING: Ten-center randomized masked comparison trial. PATIENTS: Premature infants (n = 871) <29 weeks gestational age by best obstetric estimate. INTERVENTIONS: Infants were randomly assigned to a course of treatment with Exosurf Neonatal (n = 438) or Infasurf (n = 433) at birth, and if still intubated, at 12 and 24 hours of age. Crossover treatment was allowed within 72 hours of age if severe respiratory failure (defined as two consecutive a/A PO2 ratios