Transarterial onyx embolization of cranial dural arteriovenous fistulas: long-term follow-up.

BACKGROUND AND PURPOSE: Endovascular therapy with liquid embolic agents is a common treatment strategy for cranial dural arteriovenous fistulas. This study evaluated the long-term effectiveness of transarterial Onyx as the single embolic agent for curative embolization of noncavernous cranial dural arteriovenous fistulas. MATERIALS AND METHODS: We performed a retrospective review of 40 consecutive patients with 41 cranial dural arteriovenous fistulas treated between March 2006 and June 2012 by using transarterial Onyx embolization with intent to cure. The mean age was 57 years; one-third presented with intracranial hemorrhage. Most (85%) had cortical venous drainage. Once angiographic cure was achieved, long-term treatment effectiveness was assessed with DSA and clinical follow-up. RESULTS: Forty-nine embolization sessions were performed; 85% of cranial dural arteriovenous fistulas were treated in a single session. The immediate angiographic cure rate was 95%. The permanent neurologic complication rate was 2% (mild facial palsy). Thirty-five of the 38 patients with initial cure underwent short-term follow-up DSA (median, 4 months). The short-term recurrence rate was only 6% (2/35). All patients with occlusion at short-term DSA undergoing long-term DSA (median, 28 months) had durable occlusion. No patient with long-term clinical follow-up (total, 117 patient-years; median, 45 months) experienced hemorrhage. CONCLUSIONS: Transarterial embolization with Onyx as the single embolic agent results in durable long-term cure of noncavernous cranial dural arteriovenous fistulas. Recurrence rates are low on short-term follow-up, and all patients with angiographic occlusion on short-term DSA follow-up have experienced a durable long-term cure. Thus, angiographic cure should be defined at short-term follow-up angiography instead of at the end of the final embolization session. Finally, long-term DSA follow-up may not be necessary if occlusion is demonstrated on short-term angiographic follow-up.

Intra-arterial nicardipine infusion improves CT perfusion-measured cerebral blood flow in patients with subarachnoid hemorrhage-induced vasospasm.

BACKGROUND AND PURPOSE: Our aim was to determine the effects of intra-arterial (IA) nicardipine infusion on the cerebral hemodynamics of patients with aneurysmal subarachnoid hemorrhage (aSAH)-induced vasospasm by using first-pass quantitative cine CT perfusion (CTP). MATERIALS AND METHODS: Six patients post-aSAH with clinical and transcranial Doppler findings suggestive of vasospasm were evaluated by CT angiography and CTP immediately before angiography for possible vasospasm treatment. CTP was repeated immediately following IA nicardipine infusion. Maps of mean transit time (MTT), cerebral blood volume (CBV), and cerebral blood flow (CBF) were constructed and analyzed in a blinded manner. Corresponding regions of interest on these maps from the bilateral middle cerebral artery territories and, when appropriate, the bilateral anterior or posterior cerebral artery territories, were selected from the pre- and posttreatment scans. Normalized values were compared by repeated measures analysis of variance. RESULTS: Angiographic vasospasm was confirmed in all patients. In 5 of the 6 patients, both CBF and MTT improved significantly in affected regions in response to nicardipine therapy (mean increase in CBF, 41 +/- 43%; range, -9%-162%, P = .0004; mean decrease in MTT, 26 +/- 24%; range, 0%-70%, P = .0002). In 1 patient, we were unable to quantify improvement in flow parameters due to section-selection differences between the pre- and posttreatment examinations. CONCLUSIONS: IA nicardipine improves CBF and MTT in ischemic regions in patients with aSAH-induced vasospasm. Our data provide a tissue-level complement to the favorable effects of IA nicardipine reported on prior angiographic studies. CTP may provide a surrogate marker for monitoring the success of treatment strategies in patients with aSAH-induced vasospasm.

Dangerous advances in measurements from digital subtraction angiography: when is a millimeter not a millimeter?

Aneurysms need accurate millimeters (mm). Direct millimeters were lost with digital subtraction angiography (DSA) years ago, with measurements in pixels. Advances in DSA can now give inherent millimeters. The Cerecyte aneurysm coiling trial's angiographic core lab assesses images from compact disc (CD). External fiducials for millimeter calibration are required. Of 25 cases with two 10 mm fiducials, near and far from the intensifier, the midline mean is between 9 "mm" to 15 "mm". Yet 10 mm must be 10 mm. This variance is potentially dangerous. Proprietary software seems to prohibit calibration transfer via CD to another vendor's system.

Case volumes of intra-arterial and intravenous treatment of ischemic stroke in the USA.

BACKGROUND AND PURPOSE: Ischemic stroke is a major cause of disability and death in the USA. Intravenous tissue plasminogen activator (t-PA) remains underutilized. With the development of newer intra-arterial reperfusion therapies, there is increased opportunity to address the more devastating large-vessel occlusions. We seek to identify the numbers of patients with stroke treated with intravenous and intra-arterial therapies, as well as to estimate the potential number of intra-arterial cases in the foreseeable future. METHODS: We performed a literature search to determine case volumes of intravenous t-PA use. We extrapolated the current case volume of intra-arterial stroke therapies from the numbers of cases in which the Merci retrieval device was used. In order to estimate the potential numbers of intra-arterial stroke cases, we characterized the percentage of patients with stroke who received intra-arterial therapy at two leading stroke centers. We applied these percentages to the numbers of patients with stroke seen at the top 100, 200 and 500 stroke centers by volume. RESULTS: The rate of intravenous t-PA use is 2.4-3.6%, resulting in 15 000-22 000 cases/year in the USA. The estimated case volume of intra-arterial therapies is 3500-7200 in 2006. Based on data from St. Luke's Brain and Stroke Institute and Massachusetts General Hospital, approximately 5-20% of patients with ischemic stroke can be treated with intra-arterial therapies. Extrapolating this to the top 500 stroke centers by volume, the potential number of intra-arterial cases in the USA is 10 400-41 500/year. CONCLUSION: Based on the current numbers of intra-arterial cases, our theoretical model identifies a potential for significant growth of this stroke therapy.

Preliminary experience with onyx embolization for the treatment of intracranial dural arteriovenous fistulas.

BACKGROUND AND PURPOSE: Onyx was recently approved for the treatment of pial arteriovenous malformations, but its use to treat dural arteriovenous fistulas (DAVFs) is not yet well established. We now report on the treatment of intracranial DAVFs using this nonadhesive liquid embolic agent. MATERIALS AND METHODS: We performed a retrospective analysis of 12 consecutive patients with intracranial DAVFs who were treated with Onyx as the single treatment technique at our institution between March 2006 and February 2007. RESULTS: A total of 17 procedures were performed in 12 patients. In all of the cases, transarterial microcatheterization was performed, and Onyx-18 or a combination of Onyx-18/Onyx-34 was used. Eight patients were men. The mean age was 56 +/- 12 years. Nine patients were symptomatic. There was an average of 5 feeders per DAVF (range, 1-9). Cortical venous reflux was present in all of the cases except for 1 of the symptomatic patients. Complete resolution of the DAVF on immediate posttreatment angiography was achieved in 10 patients. The remaining 2 patients had only minimal residual shunting postembolization, 1 of whom appeared cured on a follow-up angiogram 8 weeks later. The other patient has not yet had angiographic follow-up. Follow-up angiography (mean, 4.4 months) is currently available in 9 patients. There was 1 angiographic recurrence (asymptomatic), which was subsequently re-embolized with complete occlusion of the fistula and its draining vein. There was no significant morbidity or mortality. CONCLUSION: In our experience, the endovascular treatment of intracranial DAVFs with Onyx is feasible, safe, and highly effective with a small recurrence rate in the short-term follow-up.

A modified technique for using elastase to create saccular aneurysms in animals that histologically and hemodynamically resemble aneurysms in human.

BACKGROUND: Treatment of intracranial aneurysms is evolving with the development of novel therapies. It is important to have an animal model which simulates human aneurysms. We describe a new modified technique to the elastase aneurysm model which creates aneurysms that histologically and hemodynamically resemble human aneurysms. METHODS: Twelve New Zealand white rabbits underwent the aneurysm creation procedure, and 2 underwent a control procedure. In the aneurysm creation procedure, the right common carotid artery (RCCA) origin is surgically exposed and temporarily occluded with a temporary aneurysm clip. The RCCA is ligated distally, and the trapped segment is infused with elastase for 20 minutes, after which the clip is removed. In the control procedure, the RCCA is ligated distally with no elastase. Animals were assessed neurologically using a previously described rabbit neurologic grading scale and food intake scale. Intravenous digital subtraction angiography (IVDSA) was performed 21 days after the procedure. Aneurysms were harvested and stained with H&E and Verhoeff's stain. FINDINGS: All 14 rabbits had normal neurologic and food intake assessments. All 12 rabbits that underwent aneurysm creation procedures demonstrated saccular aneurysms on IVDSA. Mean aneurysm size was 5.9+/-1.9 mm; range 4.3-10.8 mm. The close proximity of the LCCA to the origin of the RCCA on the aortic arch of the New Zealand white rabbit closely resembles a bifurcation aneurysm. Both rabbits that underwent control procedures showed no aneurysm and retrograde thrombosis of the RCCA. Histologic analysis showed the aneurysms had histology characteristic of true human aneurysms. CONCLUSION: We have developed a new modified technique to the elastase aneurysm model which creates aneurysms that hemodynamically and histologically resemble human aneurysms. There have been previous elastase models described, however we find our model is easier to perform and highly reproducible. The aneurysms can be accessed transfemorally making the model ideal for testing endovascular therapies.

Motor evoked potentials predicting early recovery from paraparesis after embolisation of a spinal dural arteriovenous fistula.

SUMMARY: Spinal dural arteriovenous malformation is an increasingly diagnosed cause of ischaemic myelopathy. Though routine intraoperative monitoring has been demonstrated to be of benefit in the endovascular treatment of these lesions, its predictive value has not been well documented. We present the case of an elderly woman with progressive spastic paraparesis who demonstrated marked improvement in limb muscle motor evoked potentials of the lower extremities immediately following endovascular occlusion of the lesion. The patient subsequently showed improvement in strength, sensation and sphincter control.

Angiographic findings associated with intra-axial intracranial tumors.

Although computed tomography and, more recently, magnetic resonance imaging, have supplanted pneumoencephalography and angiography in the initial evaluation of patients with suspected intracranial neoplasms, angiography may still have an important role in the diagnosis and management of such individuals. It can define normal arterial and venous anatomy (important information in planning surgical approaches to some lesions), show vascular abnormalities associated with intracranial tumors, evaluate the integrity of the collateral circulation, incorporate functional testing for eloquent brain in the vicinity of a lesion, and be used in conjunction with the administration of intra-arterial chemotherapy.

Mediator release from mast cells by nerve growth factor. Neurotrophin specificity and receptor mediation.

Nerve growth factor causes mediator release from rat peritoneal mass cells in the presence of lysophosphatidylserine. We have investigated the neurotrophin and receptor specificity involved in this response. Nerve growth factor produced a dose-dependent release of [14C]serotonin in the presence of lysophosphatidylserine with an EC50 of approximately 1 nM. Incubation with brain-derived neurotrophic factor and neurotrophin-3 did not produce a response. Northern blot analysis with probes for low affinity nerve growth factor receptor (p75), trkA, trkB, and trkC demonstrated a detectable signal for trkA only. Western blots of trkA immunoprecipitates from mast cell culture lysates, probed with anti-phosphotyrosine antibodies, demonstrated expression of functional TrkA protein. To determine whether p75, trkB, or trkC mRNA was present in amounts below the limit of detection for Northern analysis, a sensitive reverse transcriptase polymerase chain reaction protocol was used; again rat peritoneal mast cells demonstrated only trkA. The predominant form of trkA message expressed in rat peritoneal mast cells was smaller than the neuronal form. An 18-nucleotide exon (coding for 6 amino acids in the extracellular domain) in the neuronal message was not found in the predominant mast cell trkA message. PC12 cells, a rat pheochromocytoma cell line, and dissociated rat sympathetic neurons showed both trkA and p75, but not trkB or trkC. Anterior pituitary expressed both trkB and trkC, but not trkA. To confirm the lack of expression of p75 on mast cells, 125I-nerve growth factor was chemically cross-linked to mast cells or PC12 cells and then immunoprecipitated with a monoclonal antibody specific for p75, 192-IgG; no p75 was detected. Thus, mediator release from rat peritoneal mast cells by nerve growth factor was specific and not a general property of neurotrophins, and the response was modulated through the trkA proto-oncogene. To our knowledge, this is the first description of a bone marrow-derived cell type that expresses trkA at both the mRNA and protein levels. These data provide further evidence that p75 is not necessary for nerve growth factor signal transduction.

Calcium-, calcium/calmodulin-, and calcium/phospholipid-stimulated protein phosphorylation in the rat anterior pituitary.

Calcium-dependent protein phosphorylation may be a critical step in the stimulated secretion of anterior pituitary hormones. We have noted the existence of a number of calcium-calcium/calmodulin-, and calcium/phospholipid-dependent phosphoproteins in the normal rat anterior pituitary. Cell extracts were prepared from anterior pituitary glands of male rats and phosphorylated with [gamma 32P]ATP in the presence or absence of calcium, calmodulin, and phosphatidylserine. The samples were electrophoresed on SDS-PAGE gels, autoradiographs prepared, and phosphate incorporation into specific proteins quantitated with microdensitometry. Calcium alone significantly stimulated the phosphorylation of proteins with molecular weights of 80.0-, 62.0-, 51.0-, 30.5-, and 25.0-kDa. The phosphorylation of 21.5-, 51.0-, and 80.0-kDa MW phosphoproteins was found to be phospholipid dependent. The phosphorylation of 62.0-, 51.0-, 33.0-, 30.5-, and 25.0-kDa MW phosphoproteins was found to be calcium/calmodulin kinase dependent. Calcium/calmodulin also inhibited phosphorylation of the 80.0-kDa phosphoprotein.

Meningitis in the neurosurgical patient.

In the patient with a basilar skull fracture and CSF leak, the risk of meningitis is greatly increased. The diagnosis of both leak and infection can be obscured by the patient's other injuries, and requires aggressive investigation of symptoms that suggest infection. Although the diagnosis is made with CSF cultures, when clinically suspected, treatment should begin after appropriate cultures have been obtained. Treatment should be directed against the most likely organisms, Streptococcus pneumoniae, Haemophilus influenzae, and the other organisms common to the upper respiratory tract. There are no good indications for prophylactic antibiotic usage in patients with known CSF leaks. The patient with a shunt or other CNS prosthetic device may have various manifestations of infection, depending on the type of device and its termination. Frank meningitis or ventriculitis is not always present. Diagnosis requires direct culturing of the shunt milieu, with the most frequent isolates being staphylococcal species and gram-negative enteric bacilli. The most effective therapy, for both eradication of the infection and minimization of the duration and morbidity of therapy, involves removal of the infected shunt, external drainage during parenteral antibiotic therapy, and complete replacement of hardware at the time of internalization. The postsurgical patient will not develop meningitis very frequently, but like the posttrauma patient, concurrent factors can make the diagnosis difficult. Differentiating infectious from chemical meningitis must often be initially based on CSF cell counts and chemistries alone. Treatment to cover the most likely organism, staphylococcal species and respiratory flora, should be started before the culture results are finalized.(ABSTRACT TRUNCATED AT 250 WORDS)

Cyclic AMP-dependent protein phosphorylation in the rat anterior pituitary.

The activation of cyclic adenosine 3'5'-monophosphate (cAMP)-dependent protein kinases has been implicated as an integral mechanism in stimulus-secretion coupling in the anterior pituitary. Therefore, we have investigated phosphorylation of endogenous protein substrates both in the presence and absence of cAMP in cell-free extracts of the rodent anterior pituitary. Specific phosphoprotein substrates in the rat anterior pituitary, which are phosphorylated by a cAMP-dependent protein kinase in vitro, were identified. Cyclic AMP potentiated the phosphorylation of proteins with apparent molecular weights of 85,000, 77,000, 63,000, 53,000, 39,000, and 33,000 as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Proteins with apparent molecular weights of 124,000, 93,000, 48,000, and 43,000 were phosphorylated only in the presence of cAMP and not in the basal condition. The results highlight endogenous protein substrates that may potentially be involved in cAMP-dependent stimulus-secretion coupling in the anterior pituitary.

Nerve growth factor enhances regeneration through silicone chambers.

The effect of exogenous NGF on axonal growth across a gap between sectioned ends of a sciatic nerve within silicone chambers was examined in Sprague-Dawley rats. After nerve section and surgical implantation, silicone chambers were filled with either a 1 mg/ml nerve growth factor (NGF)/saline solution (experimental) or a normal saline solution (control). Four weeks after surgery, the regenerated nerves from within the silicone chambers were dissected and fixed for histological studies at both light microscopic and ultrastructural levels. Morphological analysis of the nerves showed no difference between the NGF-treated and control groups in the size of the regenerated nerves within the chambers or in the diameters of myelinated axons. Total myelinated axonal counts were determined from within the distal chamber. NGF significantly increased the number of myelinated axons that grew into the distal end of the chamber (2126 +/- 437 NGF/saline; 1064 +/- 268 saline; P less than 0.05 Student's t test). Counts of the unmyelinated axons from the distal nerve segment from the two groups were not different. Myelin sheath thickness was 58% greater in the NGF-treated group compared with that in the saline group. There was no difference between the two groups in the size-frequency spectra of the diameters of the myelinated axons in the distal segment. The NGF/saline group showed a more mature-appearing regenerated nerve based on the percentage of myelinated axons, thickness of the myelin sheaths, and development of internal organization (e.g., amount of endoneurial collagen fibers, ensheathment of unmyelinated axons by Schwann cells, and interfascicular patterns).(ABSTRACT TRUNCATED AT 250 WORDS)

Tunicamycin prevents stimulation of protein synthesis by branched chain amino acids in isolated rat muscles.

Quarter rat diaphragms were incubated for 150 min. with or without stimulators of protein synthesis and/or inhibitors of protein glycosylation. Tyrosine incorporation into protein was measured during the last 120 min. Branched chain amino acids stimulated protein synthesis by 40-60%. Tunicamycin or 2-deoxy-D-glucose did not affect baseline protein synthesis, but inhibited or abolished stimulation of protein synthesis by branched chain amino acids. Tunicamycin did not prevent stimulation of protein synthesis by insulin or affect amino acid transport under these conditions. The data suggest that a) glycoprotein(s) may be involved in the post-transcriptional stimulation of protein synthesis by leucine, b) leucine and insulin may stimulate peptide chain initiation in muscle through different mechanisms.

Fragile sites in human chromosomes I. The effect of methionine on the Xq fragile site.

The Xq fragile site found in males having non-specific X-linked mental retardation was studied by varying the chemical and physical parameters of leukocyte cultures. Methionine was shown to be required for marker expression in both medium 199 and MEM. Banding studies indicated that methionine does not function as a stabilizing factor for the fragile site on Xq.