Internal and external effects on cognition: Evidence from memory training in very preterm-born children and cognition in patients with carotid artery stenosis before and after treatment

The present synopsis aims to integrate one study about memory training in very preterm-born children and two studies about cognition in patients with carotid artery stenosis before and after treatments. Preterm-born children are at increased risk of cognitive deficits and behavioural problems compared with peers born at term. This thesis determined whether memory training would improve cognitive functions in school-age very preterm-born children. Memory strategy training produced significant improvements in trained and non-trained cognitive functions; a core working memory training revealed significant effects on short-term memory and working memory tasks. Six months after training, children in both training groups showed better working memory performance than children in the waiting control group. This is evidence that memory training – an external influence on cognition – induces plastic changes in very preterm-born children. Patients with carotid artery stenosis are known to be at increased risk of cognitive impairment. We showed that patients with symptomatic or asymptomatic carotid artery stenosis were at higher risk for cognitive deficits than expected in a normative sample. This thesis seeks to link cognitive plasticity to internal factors like carotid stenosis. An external factor, which influences blood flow to the brain is the nature of the carotid artery stenosis treatment. Research on the effects of carotid artery stenosis treatment on cognition has produced inconsistent results. We found significant improvement in frontal lobe functions, visual memory and motor speed one year after treatment independent of the treatment type (best medical treatment, carotid artery stenting, carotid artery endarterectomy); providing evidence for ‘treatment-induced’ cognitive plasticity. Baseline performance was negatively associated with improvement in various cognitive functions after training in very preterm-born children and after treatment in patients with carotid artery stenosis. The present synopsis aims to integrate these findings into the current and relevant literature, and discuss consequences as well as methodological considerations resulting from the studies constituting the thesis at hand.

Carotid artery intimal medial thickness, brachial artery flow-mediated vasodilation and cardiovascular risk factors in diabetic and non-diabetic indigenous Australians

Background: Indigenous Australians are at high risk for cardiovascular disease and type 2 diabetes. Carotid artery intimal medial thickness (CIMT) and brachial artery flow-mediated vasodilation (FMD) are ultrasound imaging based surrogate markers of cardiovascular risk. This study examines the relative contributions of traditional cardiovascular risk factors on CIMT and FMD in adult Indigenous Australians with and without type 2 diabetes mellitus. Method: One hundred and nineteen Indigenous Australians were recruited. Physical and biochemical markers of cardiovascular risk, together with CIMT and FMD were meausred for all subjects. Results: Fifty-three Indigenous Australians subjects (45%) had type 2 diabetes mellitus. There was a significantly greater mean CIMT in diabetic versus non-diabetic subjects (p = 0.049). In the non-diabetic group with non-parametric analyses, there were significant correlations between CIMT and: age (r = 0.64, p < 0.001), systolic blood pressure (r = 0.47, p < 0.001) and non-smokers (r = -0.30, p = 0.018). In the diabetic group, non-parametric analysis showed correlations between CIMT, age (r = 0.36, p = 0.009) and duration of diabetes (r = 0.30, p = 0.035) only. Adjusting forage, sex, smoking and history of cardiovascular disease, Hb(A1c) became the sole significant correlate of CIMT (r = 0.35,p = 0.01) in the diabetic group. In non-parametric analysis, age was the sole significant correlate of FMD (r = -0.31,p = 0.013), and only in non-diabetic subjects. Linear regression analysis showed significant associations between CIMT and age (t = 4.6,p < 0.001), systolic blood pressure (t = 2.6, p = 0.010) and Hb(A1c) (t = 2.6, p = 0.012), smoking (t = 2.1, p = 0.04) and fasting LDL-cholesterol (t = 2.1, p = 0.04). There were no significant associations between FMD and examined cardiovascular risk factors with linear regression analysis Conclusions: CIMT appears to be a useful surrogate marker of cardiovascular risk in this sample of Indigenous Australian subjects, correlating better than FMD with established cardiovascular risk factors. A lifestyle intervention programme may alleviate the burden of cardiovascular disease in Indigenous Australians by reducing central obesity, lowering blood pressure, correcting dyslipidaemia and improving glycaemic control. CIMT may prove to be a useful tool to assess efficacy of such an intervention programme. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

Folate supplementation fails to affect vascular function and carotid artery intima media thickness in cyclosporin A-treated renal transplant recipients

Background: Cyclosporin A (CsA)-treated renal transplant recipients (RTR) exhibit relative hyperhomocystinemia and vascular dysfunction. Folate supplementation lowers homocysteine and has been shown to improve vascular function in healthy subjects and patients with coronary artery disease. The aim of this study was to assess the effects of 3 months of folate supplementation (5 mg/day) on vascular function and structure in RTR. Methods: A double-blind, placebo-controlled crossover study was conducted in 10 CsA-treated RTR. Vascular structure was measured as carotid artery intima media thickness (IMT) and function was assessed as changes in brachial artery diameter during reactive hyperemia (RE) and in response to glyceryl trinitrate (GTN). Function data were analyzed as absolute and percent change from baseline and area under the diameter/time curve. Blood samples were collected before and after supplementation and analyzed for total plasma homocysteine, folate, vitamin B-12 and asymmetric dimethyl arginine (ADMA) in addition to regular measures of hemoglobin, hematocrit, mean corpuscular volume (MCV) and serum creatinine. Results: Folate supplementation significantly increased plasma folate by 687% (p < 0.005) and decreased homocysteine by 37% (p < 0.05) with no changes (p > 0.05) in vitamin B 12 or ADMA. There were no significant (p > 0.05) changes in vascular structure or function during the placebo or the folate supplementation phases; IMT; placebo pre mean +/- SD, 0.52 +/- 0.12, post 0.50 +/- 0.11; folate pre 0.55 +/- 0.17, post 0.49 +/- 10.20 mm 5% change in brachial artery diameter (RH, placebo pre 10 +/- 8, post 6 +/- 5; folate pre 9 +/- 7, post 7 +/- 5; GTN, placebo pre 18 +/- 10, post 17 +/- 9, folate pre 16 +/- 9, post-supplementation 18 +/- 8). Conclusion: Three months of folate supplementation decreases plasma homocysteine but has no effect on endothelial function or carotid artery IMT in RTR.

A predictive computational fluid dynamics study of carotid artery

Abstract not available

Computed Tomography Perfusion Can Guide Endovascular Therapy in Bilateral Carotid Artery Dissection

Carotid artery dissection (CAD) is a major cause of stroke in those under age 45, accounting for around 20% of ischaemic events[1,2]. In the absence of known connective tissue disorders, most dissections are traumatic[2]. First-line management is comprised of antiplatelet or anticoagulation therapy, but many traumatic dissections progress despite this and carry the risk of long-term complications from embolism or stenosis[3]. We report a case of traumatic bilateral carotid dissection leading to progressive neurological symptoms and hypoperfusion on computed tomography perfusion (CTP), despite escalation in anticoagulation, which led to emergency carotid stenting.

A Case of Internal Carotid Artery Thrombosis associated with Thalidomide Administration in Multiple Myeloma

Thalidomide is an effective chemotherapeutic agent used to achieve remission in multiple myeloma. However, its administration is associated with several adverse effects including venous thromboembolism, while arterial thrombosis has also, although rarely, been described in the literature. We report a case of internal carotid artery occlusion within 1 week of starting thalidomide with prophylactic low molecular weight heparin in a patient who had no other prothrombotic risk factors. It is not known why this complication occurs despite the administration of anticoagulant prophylaxis. The role of factor VIII, von Willebrand factor antigen levels and fibrinogen in multiple myeloma patients should be studied in order to determine if these factors should be targeted in future prophylactic treatment.

Circulating bone marrow cells can contribute to neointimal formation

To examine the source of smooth muscle-like cells during vascular healing, C57BL/6 (Ly 5.2) female mice underwent whole body irradiation followed by transfusion with 10(6) nucleated bone marrow cells from congenic (Ly 5.1) male donors. Successful repopulation (88.4 +/- 4.9%) by donor marrow was demonstrated in the female mice by flow cytometry with FITC-conjugated A20.1/Ly 5.1 monoclonal antibody after 4 weeks. The arteries of the female mice were then subjected to two types of insult: (1) The iliac artery was scratch-injured by 5 passes of a probe causing severe medial damage. After 4 weeks, the arterial lumen was obliterated by a cell-rich neointima, with cells containing a smooth muscle actin present around the residual lumen. Approximately half of these cells were of male donor origin, as evidenced by in situ hybridization with a Y-chromosome-specific probe. (2) In an organized arterial thrombus formed by inserting an 8-0 silk suture into the left common carotid artery, donor cells staining with alpha smooth muscle actin were found in those arteries sustaining serious damage but not in arteries with minimal damage, Our results suggest that bone marrow-derived cells are recruited in vascular healing as a complementary source of smooth muscle-like cells when the media is severely damaged and few resident smooth muscle cells are available to effect repair. Copyright (C) 2001 S. Karger AG, Basel.

Neointimal formation by circulating bone marrow cells

The origin of smooth muscle cells involved in vascular healing was examined. Eighteen C57BL/6 (Ly 5.2) female mice underwent whole body irradiation followed by transfusion with 10(6) bone nucleated marrow cells from congenic (Ly 5.1) male donors. Successful repopulation by donor marrow was demonstrated after 4 weeks by flow cytometry with FITC-conjugated A20.1/Ly 5.1 monoclonal antibody. The iliac artery of six of the chimeric mice was scratch-injured by five passes of a probe, causing severe medial damage. After 4 weeks the arterial lumen was obliterated by a cell-rich neointima, with alpha-smooth muscle actin-containing cells present around the residual lumen. Approximately half of these cells were of male donor origin, as evidenced by in situ hybridization with a Y chromosome-specific probe. An organized arterial thrombus was formed in the remaining 12 chimeric mice by inserting an 8.0 silk suture into the left common carotid artery. Donor cells staining with alpha-smooth muscle actin were found in those arteries sustaining serious damage but not in arteries with minimal damage. Our results suggest that bone marrow-derived cells are recruited in vascular healing as a complementary source of smooth muscle-like cells when the media is severely damaged and few resident smooth muscle cells are available to effect repair.

Induction and maintenance of in vivo ventricular fibrillation in rabbits

Aim: To provide new sustainable in vivo models of ventricular fibrillation in rabbits. Methods: New Zealand rabbits were submitted to anaesthesia and mechanical ventilation. after which ventricular fibrillation was induced through electrical stimulation (for 2 min at 100 Hz, with 2-ms pulses, 10 mA. and 10V) directly to the heart. To that end, the animals were divided into two groups: right ventricle (n = 11) and left ventricle (n = 11). In group right ventricle, the thoracic cavity was exposed, and a catheter was introduced into the right ventricle via the right jugular vein. in group left ventricle, the thorax remained closed, and the catheter was introduced into the left ventricle via the left common carotid artery (cervical access). Results: Sustained ventricular fibrillation was achieved in 100% of group right ventricle rabbits (n = 11 and in 82% of group left ventricle rabbits (n = 9). Conclusion: Both models proved appropriate for achieving sustained ventricular fibrillation. However, in view of the invasiveness of the procedure adopted in group right ventricle, the experimental conditions used in group left ventricle seemed more physiological and more effective in inducing sustained ventricular fibrillation. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Endoscopic Anatomy of the Pterygopalatine Fossa and the Transpterygoid Approach: Development of a Surgical Instruction Model

Introduction: The pterygopalatine fossa (PPF) is a narrow space located between the posterior wall of the antrum and the pterygoid plates. Surgical access to the PPF is difficult because of its protected position and its complex neurovascular anatomy. Endonasal approaches using rod lens endoscopes, however, provide better visualization of this area and are associated with less morbidity than external approaches. Our aim was to develop a simple anatomical model using cadaveric specimens injected with intravascular colored silicone to demonstrate the endoscopic anatomy of the PPF. This model could be used for surgical instruction of the transpterygoid approach. Methods: We dissected six PPF in three cadaveric specimens prepared with intravascular injection of colored material using two different injection techniques. An endoscopic endonasal approach, including a wide nasoantral window and removal of the posterior antrum wall, provided access to the PPF. Results: We produced our best anatomical model injecting colored silicone via the common carotid artery. We found that, using an endoscopic approach, a retrograde dissection of the sphenopalatine artery helped to identify the internal maxillary artery (IMA) and its branches. Neural structures were identified deeper to the vascular elements. Notable anatomical landmarks for the endoscopic surgeon are the vidian nerve and its canal that leads to the petrous portion of the internal carotid artery (ICA), and the foramen rotundum, and V2 that leads to Meckel`s cave in the middle cranial fossa. These two nerves, vidian and V2, are separated by a pyramidal shaped bone and its apex marks the ICA. Conclusion: Our anatomical model provides the means to learn the endoscopic anatomy of the PPF and may be used for the simulation of surgical techniques. An endoscopic endonasal approach provides adequate exposure to all anatomical structures within the PPF. These structures may be used as landmarks to identify and control deeper neurovascular structures. The significance is that an anatomical model facilitates learning the surgical anatomy and the acquisition of surgical skills. A dissection superficial to the vascular structures preserves the neural elements. These nerves and their bony foramina, such as the vidian nerve and V2, are critical anatomical landmarks to identify and control the ICA at the skull base.

An anatomical study on the lingual-facial trunk

Purpose We quantified variations of the lingual artery origin, measured the lingual artery origin distance from clinical relevant landmarks and compared the lingual artery diameters with normal and variable origin. Methods Forty-two formalin fixed male cadavers were bilaterally evaluated. Measurements were performed with the aid of an electronic digital caliper. Results The origin distances from the common carotid artery bifurcation was 1.05 +/- 0.11 and 1.02 +/- 0.11 cm for the right and left lingual arteries respectively with no differences compared to the lingual-facial trunks. The diameters of the lingual arteries were 0.25 +/- 0.01 and 0.26 +/- 0.01 cm for the right and left sides, respectively, while the lingual facial trunks showed diameters of 0.21 +/- 0.02 and 0.24 +/- 0.02 cm for the right and left sides, respectively. Conclusions The present study adds information on the lingual artery diameter and its anatomical relation to clinically useful landmarks.