Chronic fusiform extracranial vertebral artery aneurysm with recurrent posterior circulation emboli: Case report and review of the literature.

We report a case of a 64-year-old man with a fusiform right extracranial vertebral artery aneurysm, spanning over half the extra-cranial V2 (foraminal) segment, presenting with recurrent multi-focal posterior circulation embolic ischaemic stroke. The patient was treated with endovascular embolisation of the right vertebral artery to prevent further thrombo-embolic events. Distal and proximal occlusion of the aneurysmal vertebral artery was performed with a micro-vascular plug with partial aneurysm sack embolisation to aid thrombosis and reduce the risk of recanalisation. Two months post procedure MR angiography confirmed successful aneurysm occlusion with no post-procedural complication. The patient returned to his normal independent life. Endovascular treatment with vessel sacrifice is an effective treatment with low morbidity and we believe the MVP device to be a efficacious option in the vertebral artery.

Skull base aneurysmal bone cyst presenting with hydrocephalus: progressive residuum obliterated by Gamma Knife stereotactic radiosurgery in a pediatric patient.

Aneurysmal bone cysts (ABCs) are an uncommon entity predominantly encountered in the pediatric population. The skull is rarely involved, but these cysts have been reported to arise in the skull base. Traditional treatment has been with surgery alone; however, there is a gathering body of literature that reports alternative treatments that can achieve long-term disease-free survival. However, these therapies are predominantly directed at peripheral skeletal lesions. To the authors' knowledge, this report is the first to describe long-term follow-up of the efficacy of Gamma Knife stereotactic radiosurgery for treatment of ABC residuum in the skull base that resulted in long-term patient stability and likely ABC obliteration.

Foetal radiation exposure caused by mechanical thrombectomy in large-vessel ischaemic stroke in pregnancy.

PURPOSE: There is overwhelming evidence for the clinical benefits that are derived following mechanical thrombectomy in large-vessel acute ischaemic stroke. The risk of stroke is elevated in pregnancy due to many factors. To date, there have been two reports, totalling five patients, who have undergone mechanical thrombectomy in pregnancy, thus demonstrating the feasibility of the procedure; however, there is no data on the radiation exposure to the mother or foetus related to this therapy. METHODS: We highlight the important technical considerations to minimise the risk of the procedure and report the estimated dose received by mother and foetus. We also compare these doses with those received during whole-body CT in trauma and CT pulmonary angiogram (CTPA) examinations. RESULTS: Three cases of mechanical thrombectomy were performed at separate tertiary referral neuroscience centres in the UK. Following diagnostic CT and mechanical thrombectomy, the total whole-body effective dose to the pregnant patient was significantly higher than in patients undergoing CTPA (p < 0.05), but not significant different compared to whole-body CT imaging in trauma patients. The estimated dose received by the foetus following diagnostic CT and mechanical thrombectomy was significantly lower than in whole-body imaging in trauma patients at p < 0.05, with no difference in estimated foetal dose compared to CTPA imaging. CONCLUSION: The estimated doses received by the foetus during diagnostic stroke imaging and mechanical thrombectomy are equivalent to, or less than, purely diagnostic imaging in emergency situations.

Persistent hypoglossal artery aneurysm: Case report and qualitative systematic review.

A persistent hypoglossal artery was first described in 1889 and is one of the more common anatomical variations arising from aberration in normal development. Endovascular coiling has been recognised as a robust treatment for acutely ruptured intracranial arterial aneurysms, although specific data regarding an aneurysm arising from a persistent hypoglossal artery is lacking due to the low incidence. Here we report both the oldest patient reported to be treated with a persistent hypoglossal artery-associated aneurysm and also explicitly report endovascular treatment of a persistent hypoglossal artery aneurysm arising at the posterior inferior cerebellar artery origin. Qualitative systematic review of the available medical literature demonstrates limited evidence regarding treatment of persistent hypoglossal artery-associated aneurysms with the majority being carried out via open surgery. Ruptured posterior inferior cerebellar artery aneurysm arising from a persistent hypoglossal artery can be successfully and safely treated by endovascular therapy via the persistent hypoglossal artery. Randomised study of this situation is unlikely to be feasible; however, qualitative review of the literature reveals six such aneurysms that have been treated surgically, and this case appears to be the first via an endovascular means.

Cervical cord decompression following embolisation of a giant cervical vertebro-vertebral arteriovenous fistula.

Arteriovenous fistulation between the vertebral arteries to extradural (epidural) veins, termed vertebro-vertebral arteriovenous fistulae, are uncommon diagnoses without established diagnostic algorithms or treatment options. Minimal evidence exists describing the management of this pathology. Endovascular treatment was performed under general anaesthesia by coil occlusion of the vertebral artery from the point of the fistula to the mid-vertebral artery. Repeat magnetic resonance angiographic imaging one week following the procedure confirmed an 80% reduction in the size of the epidural vein and decompression of the cervical spinal cord. At four-week follow-up there was significant qualitative improvement in the myelopathic symptoms including walking distance and pain. Normal physiological filling of the collapsed extradural vein was observed on follow-up digital subtraction angiography at five months. Catheter angiography by an experienced interventional neuro-radiologist is critical in defining the anatomy and providing minimally invasive treatment.

Mouse kidney transplantation: models of allograft rejection.

Rejection of the transplanted kidney in humans is still a major cause of morbidity and mortality. The mouse model of renal transplantation closely replicates both the technical and pathological processes that occur in human renal transplantation. Although mouse models of allogeneic rejection in organs other than the kidney exist, and are more technically feasible, there is evidence that different organs elicit disparate rejection modes and dynamics, for instance the time course of rejection in cardiac and renal allograft differs significantly in certain strain combinations. This model is an attractive tool for many reasons despite its technical challenges. As inbred mouse strain haplotypes are well characterized it is possible to choose donor and recipient combinations to model acute allograft rejection by transplanting across MHC class I and II loci. Conversely by transplanting between strains with similar haplotypes a chronic process can be elicited were the allograft kidney develops interstitial fibrosis and tubular atrophy. We have modified the surgical technique to reduce operating time and improve ease of surgery, however a learning curve still needs to be overcome in order to faithfully replicate the model. This study will provide key points in the surgical procedure and aid the process of establishing this technique.

Macrophages and transplant rejection: a novel future target?

In this issue of Transplantation, Ma et al. describe the protective effect of administering the c-fms kinase inhibitor upon cellular rejection, suggesting an important pathogenic role for macrophages. In contrast, no effect upon the development of humerol rejection was evident. The role of macrophages in rejection is discussed.

A comparative study of 2 computer-assisted methods of quantifying brightfield microscopy images.

Immunohistochemistry continues to be a powerful tool for the detection of antigens. There are several commercially available software packages that allow image analysis; however, these can be complex, require relatively high level of computer skills, and can be expensive. We compared 2 commonly available software packages, Adobe Photoshop CS6 and ImageJ, in their ability to quantify percentage positive area after picrosirius red (PSR) staining and 3,3'-diaminobenzidine (DAB) staining. On analysis of DAB-stained B cells in the mouse spleen, with a biotinylated primary rat anti-mouse-B220 antibody, there was no significant difference on converting images from brightfield microscopy to binary images to measure black and white pixels using ImageJ compared with measuring a range of brown pixels with Photoshop (Student t test, P=0.243, correlation r=0.985). When analyzing mouse kidney allografts stained with PSR, Photoshop achieved a greater interquartile range while maintaining a lower 10th percentile value compared with analysis with ImageJ. A lower 10% percentile reflects that Photoshop analysis is better at analyzing tissues with low levels of positive pixels; particularly relevant for control tissues or negative controls, whereas after ImageJ analysis the same images would result in spuriously high levels of positivity. Furthermore comparing the 2 methods by Bland-Altman plot revealed that these 2 methodologies did not agree when measuring images with a higher percentage of positive staining and correlation was poor (r=0.804). We conclude that for computer-assisted analysis of images of DAB-stained tissue there is no difference between using Photoshop or ImageJ. However, for analysis of color images where differentiation into a binary pattern is not easy, such as with PSR, Photoshop is superior at identifying higher levels of positivity while maintaining differentiation of low levels of positive staining.

Shockwave lithotripsy: arterial aneurysms and vascular complications.

BACKGROUND AND PURPOSE: The application of shockwave lithotripsy (SWL) in patients with arterial aneurysm remains controversial, and several case reports exist in the world literature that describe both safe use and rupture. In addition, other vascular complications have been reported. The potential for hemorrhage is affected by coagulation status and antiplatelet therapy, yet little evidence exists on their interaction with SWL. We aim to review the vascular complications after SWL. METHODS: A review of the world literature was performed in accordance with methodology that is defined by the Cochrane Collaboration. An Internet bibliographic search on MEDLINE was performed during May and June 2010, with additional hand-searching of references. The search terms lithotripsy, aneurysm, abdominal aortic aneurysm, pseudoaneurysm, hemorrhage, hematoma, coagulation, aspirin, clopidogrel, and warfarin were used. RESULTS: In reported cases, there have been 18 patients with abdominal aortic aneurysm (AAA) who have undergone SWL. Both safe and uncomplicated treatment have been reported as well as rupture of AAA. Other vascular complications after SWL have included pseudoaneurysm, venous thrombosis, arterial stenosis, and arteriovenous fistulation. Patients with hemorrhagic risk factors can undergo SWL after correction of coagulopathy. Experimental work on animal models and human tissue has evaluated the effects of SWL on the vasculature. CONCLUSION: There is currently no high-level evidence to suggest that SWL in the presence of arterial aneurysm is unsafe. Experimental work on ex vivo human tissue does not suggest that SWL is causative to aneurysm rupture. With the availability of CT imaging in modern clinical practice, aneurysms of the arterial tree should be identified as part of the investigation of urinary tract calculi. SWL can be safely performed in patients with AAA, but monitoring postprocedure is mandatory, along with access to emergency vascular surgery support; importantly, any onset of new pain or symptoms should be aggressively investigated by radiologic imaging in the first instance.

Vascular B1 kinin receptors in patients with congestive heart failure.

Animal models suggest a vasomotor role for the B1 kinin receptor in cardiovascular disease states. In patients with heart failure treated with angiotensin-converting enzyme inhibition (ACEi), or combined B1/B2 receptor antagonism, but not B2 receptor antagonism alone, causes vasoconstriction. However, B1 agonism has no effect on vasomotor or fibrinolytic function. Findings from transgenic animals lacking the B2 receptor suggest that these conflicting data may be explained by cross-talk between B1 and B2 receptors. We hypothesized that B1 stimulation causes vasodilatation and tissue plasminogen activator release in the human forearm when B2 receptor signaling is inhibited. Forearm blood flow was measured in 16 patients with heart failure receiving ACEi. In double-blinded crossover studies, intrabrachial Lys-[Leu8]-des-Arg9-bradykinin (B1 antagonist), lys-des-Arg9-bradykinin (B1 agonist), bradykinin (B2 agonist), and sodium nitroprusside (endothelium-independent vasodilator) were infused alone or with HOE-140 (B2 antagonist). HOE-140 did not affect basal vascular tone or t-PA release, but it abolished bradykinin-induced vasodilatation and t-PA release (P < 0.0001). Blood flow and t-PA release were unaffected by B1 agonism or antagonism in the presence and absence HOE-140. Our findings do not support a role for crosstalk between the B1 and B2 kinin receptors in the human peripheral circulation.

Prolonged toxicity after massive olanzapine overdose: two cases with confirmatory laboratory data.

Olanzapine is a second-generation atypical antipsychotic that is increasingly used in preference to older antipsychotic agents. Limited data is available concerning the toxic effects of olanzapine after deliberate overdose. Two patients presented to our institution after massive olanzapine ingestion, and required prolonged ventilatory support due to the development of coma and respiratory depression. Serum olanzapine concentrations were orders of magnitude higher than those associated with therapeutic doses, and remained elevated for several days after ingestion. Both patients made a full recovery with only supportive care, despite having initial serum drug concentrations > 2500 microg/l. These reports indicate the potential for olanzapine ingestion to cause coma that may persist for several days after overdose.

B1 kinin receptor does not contribute to vascular tone or tissue plasminogen activator release in the peripheral circulation of patients with heart failure.

OBJECTIVE: Vascular expression of the B1 kinin receptor is markedly upregulated with left ventricular dysfunction and angiotensin-converting enzyme (ACE) inhibition, but its function remains unclear. Inhibitors of ACE potentiate bradykinin-mediated B2 receptor-dependent vasodilatation and tissue plasminogen activator (tissue-type plasminogen activator [t-PA]) release. We investigated the contribution of the B1 receptor to the maintenance of vascular tone and t-PA release in patients with heart failure. METHODS AND RESULTS: Eleven patients were treated with enalapril (10 mg twice daily) or losartan (50 mg twice daily) in a randomized double-blind crossover trial. During week 6 of each treatment, patients received an intrabrachial infusion of Lys-des-Arg9-bradykinin (B1 agonist; 1 to 10 nmol/min), bradykinin (30 to 300 pmol/min), Lys-[Leu8]-des-Arg9-bradykinin (B1 antagonist; 1 to 10 nmol/min), and norepinephrine (60 to 540 pmol/min). Blood flow and t-PA release were measured using venous occlusion plethysmography and blood sampling. Bradykinin (P<0.001 for all), but not Lys-des-Arg9-bradykinin, caused vasodilatation and t-PA antigen and activity release. Norepinephrine (P<0.001), but not Lys-[Leu8]-des-Arg9-bradykinin, caused vasoconstriction. Compared with losartan, enalapril augmented bradykinin-mediated vasodilatation (P<0.05) and t-PA release (P<0.01 for all) but had no effect on B(1) receptor-mediated responses. CONCLUSIONS: The B1 kinin receptor does not have a major vasomotor or fibrinolytic role in patients with heart failure. Augmentation of kinin-mediated vasodilatation and t-PA release by ACE inhibition is restricted to the B2 receptor.