Cerebrovascular disease in sickle cell disease.

Sickle cell disease (SCD) is the most common type of hereditary anaemia and genetic disorder worldwide. Cerebrovascular disease is one of its most devastating complications, with consequent increased morbidity and mortality. Current guidelines suggest that children and adults with SCD who develop acute ischaemic stroke should be transfused without delay. Those with acute ischaemic stroke aged over 18 years who present within 4.5 hours of symptom onset should be considered for intravenous thrombolysis; older patients with conventional vascular risk factors are the most likely to benefit. Endovascular thrombectomy should be considered carefully in adults with SCD as there are few data to guide how the prevalence of cerebral vasculopathy may confound the expected benefits or risks of intervention. We present a practical approach to cerebrovascular disease in sickle cell patients based on the available evidence and our experience.

Management of a wake-up stroke.

Current national guidelines advocate intravenous thrombolysis to treat patients with acute ischaemic stroke presenting within 4.5 hours from symptom onset, and thrombectomy for patients with anterior circulation ischaemic stroke from large vessel occlusion presenting within 6 hours from onset. However, a substantial group of patients presents with acute ischaemic stroke beyond these time windows or has an unknown time of onset. Recent studies are set to revolutionise treatment for these patients. Using MRI diffusion/FLAIR (fluid-attenuated inversion recovery) mismatch, it is possible to identify patients within 4.5 hours from onset and safely deliver thrombolysis. Using CT perfusion imaging, it is possible to identify subjects with a middle cerebral artery syndrome who have an extensive area of ischaemic brain but as yet have only a small area of infarction who may benefit from urgent thrombectomy in up to 24 hours. Here, we highlight the recent advances in late window stroke treatment and their potential contribution to clinical practice.

Prospective comparison of late 3T MRI with conventional angiography in evaluating the patency of cerebral arteriovenous malformations treated with stereotactic radiosurgery.

INTRODUCTION: Risk of further haemorrhage in patients suffering from arteriovenous malformation (AVM) would be eliminated only if complete obliteration of the AVM is obtained. Therefore, these patients frequently need long-term follow-up. Conventional catheter angiography (CCA) with a risk of 0.5 %.to 1.6 % of significant neurological complications has traditionally been used for this purpose. However, magnetic resonance imaging (MRI) at 3T may be a safer alternative. The aim of this study was to evaluate if MRI at 3T can accurately evaluate closure of AVM in 2 years after stereotactic radiosurgery. METHODS: Twenty-three patients with both MRI at 3T and a CCA study were examined. The residual AVMs were evaluated by MRI at 3T against CCA in a prospective study. RESULTS: The time interval between radiosurgery and neuroimaging was on average of 25 months (range, 15-30 months) for MRI study and 33 months (range, 25-46 months) for CCA study. Ten patients showed closure of the AVM on MRI, all of which were confirmed on CCA. CONCLUSION: There was a complete agreement between late MRI at 3T scan and CCA in evaluation of AVM patency.

Craniospinal abnormalities and neurologic complications of osteogenesis imperfecta: imaging overview.

Osteogenesis imperfecta is a rare genetic disorder that leads to progressive skeletal deformities due to deficits in type I collagen, the main pathophysiologic effect of the disease. In addition, it may lead to a wide range of associated neurologic abnormalities: The central nervous system is usually involved because of softening of bone at the base of the skull, with resultant upward migration of the upper cervical spine and odontoid process into the skull base. Upward migration of the spine may cause compression of the brainstem, mechanical impingement of the spinal canal with restriction of cerebrospinal fluid circulation, and impingement of the cranial nerves. Osteogenesis imperfecta also may directly involve neurovascular structures, leading to cavernous fistulas of the carotid artery, dissection of the cervical arteries, and cerebral aneurysms. The brain parenchyma is frequently affected by the disease, with manifestations including cerebral atrophy, communicating hydrocephalus, and cerebellar hypoplasia. The imaging features of the disorder vary as widely as its clinical manifestations, depending on the severity of disease. Severe forms accompanied by debilitating skeletal fractures and progressive neurologic impairments may lead to perinatal death, whereas milder asymptomatic forms might cause only a modest reduction in life span. The most important advance in medical therapy for osteogenesis imperfecta has been the introduction of bisphosphonate therapy to slow the resorption of bone in patients with moderate to severe forms of the disease (ie, type III or IV). In some patients, neurosurgery may be necessary to correct the effects of severe basilar invagination by the odontoid process.

Stereotactic radiosurgery for pineal tumours.

OBJECTIVES: Pineal tumours continue to present considerable clinical dilemmas and challenges. We were, therefore, interested to review our cumulative experience with a view to formulating a potential treatment strategy. METHODS: A retrospective analysis of all patients treated with Stereotactic radiosurgery (SRS) for pineal tumours in one centre between 1987 and 2009. Forty-four patients (66% male) were treated radiosurgically with a mean age(± 1 sd) of 33.6 (16.4) years. Eleven had biopsy-proven pineal parenchymal tumours (PPT), six astrocytomas, three ependymomas, two papillary epithelial tumours and two germ cell tumours. Twenty (45%) patients had no definitive histology despite attempted surgical biopsy in 11. Prior to radiosurgery, 17 had undergone craniotomy, 10 radiotherapy and four chemotherapy. Nine patients were referred for primary SRS. RESULTS: Fifty Gamma knife treatments were performed on 44 patients prescribing 18.1 (4.2) Gy with a treatment volume of 3.8 (3.8) cm( 3 ). Routine clinical and MRI assessments were reviewed to calculate control rates. Mean follow up was 62.5 (52.9) months. Five patients (two ependymomas and three PPT) died at 36.2 (36.7) months after initial radiosurgical treatment. Overall progression-free survival (PFS) results were 93% at 1 year, 77% at 5 years, 67% at 10 and 20 years. Log-rank analysis revealed that higher initial tumour grade (P = 0.04), previous radiotherapy (P = 0.002) and radiological evidence of necrosis (P = 0.03) were associated with worse outcomes. The 5-year PFS for patients who possessed these 'aggressive' features was 47.1% compared with 91% for those patients who did not have these features. No persistent complications were attributed to SRS. CONCLUSIONS: These results further demonstrate the increasingly significant role played by STRS in the treatment of pineal tumours. Based on our findings, we believe a re-examination of the role of more established therapies for this patient group may be warranted.

Peripheral arterial disease and methylenetetrahydrofolate reductase (MTHFR) C677T mutations: A case-control study and meta-analysis.

OBJECTIVE: Hyperhomocysteinaemia is associated with peripheral arterial disease (PAD). There are inter-individual variations in the metabolism of homocysteine because of genetic polymorphisms. This study analyzed the role of one polymorphism that is associated with raised homocysteine, as a risk factor for PAD. METHODS: This study considered the association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms with the incidence of PAD by performing a case-control study and a cross sectional study of homocysteine levels. We recruited 133 patients with PAD in Norfolk and compared the MTHFR allele distribution with 457 healthy individuals. We also carried out a meta-analysis to place our data within the context of other published studies. We searched Medline, Embase, and Cochrane databases up to March 2008 for any studies on the association between MTHFR C677T polymorphism and PAD. RESULTS: The MTHFR C677T allele frequencies in the cases and controls were 0.37 and 0.33, and the odds ratios for the association of the 677 T allele or TT genotype with PAD were 1.18 (95% Confidence Interval [CI] 0.89, 1.58) and 1.99 (95% CI 1.09, 3.63). Homozygotes for the MTHFR C677T mutation had higher concentrations of plasma total homocysteine, odds ratio 2.82 (95% CI 1.03, 7.77) compared to homozygotes for the MTHFR 677 CC genotype. Twelve of 72 articles retrieved from the database search reported the prevalence of mutations in PAD patients. A meta-analysis of 9 appropriate studies, including our own, showed that being homozygous for the C677T allele was associated with an increased risk of PAD, pooled odds ratio 1.36 (95% CI 1.09, 1.68). CONCLUSION: We have found a strong association between raised homocysteine, the TT genotype, and PAD.

The effects of increasing obesity on outcomes of vascular surgery.

The aim of this study was to determine whether vascular patients are becoming progressively more obese and whether morbid obesity affects outcomes from vascular surgery. Data for the index vascular procedures of infrainguinal bypass, carotid endarterectomy, and abdominal aortic aneurysm (AAA) repair were collected in a computer database for 1996-2006. Body mass index (BMI) was stratified into <18.5 kg/m2 as underweight, >35 kg/m2 as morbidly obese, and other as control (18.5 < BMI < 35). The data were analyzed with respect to operation duration, length of stay, complication rates, and mortality rates. Results were adjusted for potential confounding variables, including mode of admission, diabetes, cardiac history, renal function, and smoking. A total of 1,317 patients were reviewed, and 1,105 cases were deemed suitable for analysis. The incidence of morbid obesity increased in a linear manner from 1.3% to 9% over the 10-year period. The operation duration was longer for morbidly obese subjects compared with normals. This was only statistically significant for AAA repair category, with a mean operating time of 158.4 +/- 65.5 min for patients with BMI <35 kg/m2 vs. 189.8 +/- 92.2 min for morbidly obese patients (p < 0.014). Infection rates were consistently higher in the morbidly obese group; however, this reached a statistically significant rate among AAA repair cases (43.5% [n = 16] vs. 34.8% [n = 159], p < 0.004). There were no significant differences in other complications, graft failure, length of stay, or mortality. Vascular patients are becoming progressively more obese. Procedures performed on morbidly obese subjects take longer, and these patients have higher rates of infectious complications. This is mainly attributable to AAA. This did not translate into poorer final outcomes in this study, although significant differences might emerge from a larger sample.

Are Aortic Stent Grafts Safe in Pregnancy?

Aortic stent grafts are increasingly used to treat aortic aneurysms and also other aortic pathologies. The safety of aortic stent grafts in pregnancy has never been studied or reported. We report on two cases of aortic stent grafts in pregnant women and discuss the effect of pregnancy on these aortic stent grafts.

Do novel risk biomarkers reflect the severity of peripheral arterial disease?

The association between novel atherosclerotic risk biomarkers and severity of peripheral arterial disease (PAD) was assessed. Patients (n = 133) with PAD were recruited. Established risk biomarkers including low- and high-density cholesterol, triglycerides, and blood pressure were measured. Novel risk biomarkers including plasma C-reactive protein, von Willebrand factor (vWF), interleukin 6, red cell folate (RCF), vitamin B12, total homocysteine (tHcy), and Hcy genotypes were also determined. The severity of PAD was evaluated, using ankle-brachial pressure index (ABPI), brachial-knee, and brachial-ankle pulse wave velocity (bk- and ba-PWV). Plasma tHcy and systolic blood pressure had a positive independent correlation with bk-PWV (ß = +0.56, P = .02 and ß = +0.38, P < .001, respectively). Red cell folate had an independent inverse correlation with bk-PWV (ß = -0.01, P = .01). Systolic blood pressure showed an independent positive correlation with ba-PWV only after adjustment for other risk biomarkers (ß = +0.1, P = .04). Novel markers, plasma tHcy, and RCF levels correlated with the severity of PAD.

Photoplethysmography, an easy and accurate method for measuring ankle brachial pressure index: can photoplethysmography replace Doppler?

OBJECTIVE: To assess the accuracy of ankle brachial pressure index (ABPI) assessed by photoplethysmography (PPG) compared with continuous wave Doppler (CW-Doppler). METHODS: Ankle brachial pressure index was measured in a standard manner using both PPG and Doppler probes. For PPG-ABPI, a PPG probe was placed on the index finger and great toe, and a microcomputer determined the ABPI. These values were compared with the ABPI measured manually using an 8-MHz Doppler probe. Correlation and agreement between PPG and Doppler ABPI were assessed by Lin's correlation coefficient and Bland-Altman plots. RESULTS: In all, 133 claudicants were assessed. There was a strong correlation between the 2 ABPI methods (beta = .79 and 95% limits of agreement of -0.23 to 0.24). CONCLUSION: Measuring ABPI automatically using the PPG technique is an effective alternative for Doppler ABPI. PPG-ABPI is completely objective, fast, and accurate.

The association between ankle brachial pressure index and pulse wave velocity: clinical implication of pulse wave velocity.

OBJECTIVE: The aim of this study was to assess the relationship between ankle brachial pressure index and pulse wave velocity in patients with peripheral arterial disease. METHODS: Brachial-knee and brachial-ankle pulse wave velocity were measured by pneumoplethysmography using cuffs in a standard technique. Correlation between pulse wave velocity and Doppler-ankle brachial pressure index was assessed by Spearman correlation and receiver operating curves. RESULTS: A total of 133 claudicants were assessed. Analysis by developing receiver operating curves for ankle brachial pressure index and pulse wave velocity showed that patients with ankle brachial pressure index over 0.6 were more likely to have a bk-pulse wave velocity over 9.2 m/s and ba-pulse wave velocity over 9.5 m/s. CONCLUSION: These results show for the first time that nondiabetic vascular patients may have measurable significant arterial stiffness independent of an impaired ankle brachial pressure index. These data suggest that pulse wave velocity may be valuable in screening and evaluating the severity of peripheral arterial disease.

Assessment of a multifactorial risk index for predicting postoperative pneumonia after open abdominal aortic aneurysm repair.

Pneumonia is a common postoperative complication, with a mortality of up to 40%. The Post-operative Pneumonia Risk Index (PPRI) was derived from a large cohort of general surgical patients but has not been validated in patients undergoing open abdominal aortic aneurysm (AAA) repair. The PPRI was applied to patients undergoing elective open AAA repair in a tertiary referral vascular unit. Pneumonia occurred in 20% of patients. Receiver operating characteristic curve analysis identified 36 as the optimum PPRI cutoff value. At this cutoff, the likelihood ratio for pneumonia was 1.35 (95% confidence interval 1.08-1.62). However, in a multivariate analysis, only weight loss in excess of 10% over the preceding 6 months was an independent predictor of postoperative pneumonia. Although the PPRI is of some value in identifying high-risk patients undergoing AAA repair, weight loss alone may be predictive, allowing targeted preventive measures in aneurysm patients at increased risk.

Are femorodistal bypass grafts for acute limb ischemia worthwhile / Vantagem associada ao uso de enxertos femorodistais para isquemia aguda de membros

Background: It has been shown that autogenous veins are associated with the best limb salvage rates for femorodistal bypass surgery. However, in emergency settings, when an autogenous vein is unavailable, use of synthetic graft material or amputation is a critical decision to make. Objective: To assess the appropriateness of femorodistal bypass grafts for acute limb ischemia in emergency settings. Methods: Patients who underwent emergent bypass and elective femorodistal bypass surgery between 1996 and 2006 were reviewed retrospectively in a single center. Results: There were 147 patients of which 84 had elective and 63 had emergent bypass. The graft patency rates for elective admissions were 44 and 25 percent vs. 25 and 23 percent for admissions for acute femorodistal graft surgery at 2 and 4 years, respectively (p < 0.004). Admissions for acute ischemia who were treated with prosthetic grafts had a primary patency of 24 vs. 27 percent for vein grafts at 2 years and 24 vs. 23 percent at 4 years (p = 0.33). In the acute femorodistal grafts group, primary patency at 2 years for vein and prosthetic grafts was 27 and 24 percent as compared to 42 and 32 percent for electives. These values for cumulative limb salvage rates for elective bypasses were 73 and 63 percent as compared to 52 percent at both time points in the acute femorodistal graft group (p < 0.004). In emergency settings, the limb salvage rate for acute femorodistal bypass with prosthetic grafts was 38 percent, and for vein grafts it was 62 percent at both time points (p = 0.08). Conclusion: The long term limb salvage rate of 38 percent suggests that emergent femorodistal revascularization is worthwhile.

Contexto: Já foi mostrado que veias autógenas estão associadas às melhores taxas de salvamento de membros para a cirurgia de bypass femorodistal. No entanto, em cenários de emergência, quando não há uma veia autógena disponível, é crítica a decisão entre o uso de material de enxerto sintético ou a amputação. Objetivo: Avaliar a adequação de enxertos femorodistais para isquemia aguda de membros em cenários de emergência. Métodos: Pacientes submetidos a cirurgia de bypass de urgência e cirurgia de bypass femorodistal eletiva entre 1996 e 2006 foram retrospectivamente revisados em um único centro. Resultados: Havia 147 pacientes, dentre os quais 84 haviam sido submetidos à cirurgia de bypass eletiva e 63 à cirurgia de bypass de urgência. As taxas de patência dos enxertos para internações eletivas foram 44 e 25 por cento versus 25 e 23 por cento para internações para cirurgia aguda de enxerto femorodistal a dois e quatro anos, respectivamente (p < 0,004). Internações por isquemia aguda que foram tratadas com enxertos prostéticos tiveram patência primária de 24 versus 27 por cento para enxertos venosos a 2 anos e 24 versus 23 por cento a 4 anos (p = 0,33). No grupo de enxertos femorodistais agudos, patência primária a 2 anos para enxertos venosos e prostéticos foi de 27 e 24 por cento, comparado a 42 e 32 por cento para eletivas. Esses valores para taxas de salvamento de membros em bypasses eletivos foram 73 e 63 por cento, comparadas a 52 por cento em ambos pontos no tempo para o grupo de enxerto femorodistal agudo (p < 0,004). Em cenários de emergência, a taxa de salvamento de membros para bypass femorodistal com enxertos prostéticos foi de 38 por cento e para enxertos venosos a taxa foi de 62 por cento em ambos pontos no tempo (p = 0,08). Conclusão: A taxa de 38 por cento para salvamento de membros a longo prazo indica que a revascularização femorodistal de urgência é vantajosa.