Computer planning of stereotactic iodine-125 seed brachytherapy for recurrent malignant gliomas

At St Thomas' Hospital, we have developed a computer program on a Titan graphics supercomputer to plan the stereotactic implantation of iodine-125 seeds for the palliative treatment of recurrent malignant gliomas. Use of the Gill-Thomas-Cosman relocatable frame allows planning and surgery to be carried out at different hospitals on different days. Stereotactic computed tomography (CT) and positron emission tomography (PET) scans are performed and the images transferred to the planning computer. The head, tumour and frame fiducials are outlined on the relevant images, and a three-dimensional model generated. Structures which could interfere with the surgery or radiotherapy, such as major vessels, shunt tubing etc., can also be outlined and included in the display. Catheter target and entry points are set using a three-dimensional cursor controlled by a set of dials attached to the computer. The program calculates and displays the radiation dose distribution within the target volume for various catheter and seed arrangements. The CT co-ordinates of the fiducial rods are used to convert catheter co-ordinates from CT space to frame space and to calculate the catheter insertion angles and depths. The surgically implanted catheters are after-loaded the next day and the seeds left in place for between 4 and 6 days, giving a nominal dose of 50 Gy to the edge of the target volume. 25 patients have been treated so far.

Familial recurrence risks for multiple sclerosis in Australia

BACKGROUND: Genetic susceptibility to multiple sclerosis (MS) has been recognised for many years. Considerable data exist from the northern hemisphere regarding the familial recurrence risks for MS, but there are few data for the southern hemisphere and regions at lower latitude such as Australia. To investigate the interaction between environmental and genetic causative factors in MS, the authors undertook a familial recurrence risk study in three latitudinally distinct regions of Australia. METHODS: Immediate and extended family pedigrees have been collected for three cohorts of people with MS in Queensland, Victoria and Tasmania spanning 15° of latitude. Age of onset data from Queensland were utilised to estimate age-adjusted recurrence rates. RESULTS: Recurrence risks in Australia were significantly lower than in studies from northern hemisphere populations. The age-adjusted risk for siblings across Australia was 2.13% compared with 3.5% for the northern hemisphere. A similar pattern was seen for other relatives. The risks to relatives were proportional to the population risks for each site, and hence the sibling recurrence-risk ratio (λ(s)) was similar across all sites. DISCUSSION: The familial recurrence risk of MS in Australia is lower than in previously reported studies. This is directly related to the lower population prevalence of MS. The overall genetic susceptibility in Australia as measured by the λ(s) is similar to the northern hemisphere, suggesting that the difference in population risk is explained largely by environmental factors rather than by genetic admixture.

Computational fluid dynamic analysis of intracranial aneurysmal bleb formation

Background The management of unruptured aneurysms is controversial with the decision to treat influenced by aneurysm characteristics including size and morphology. Aneurysmal bleb formation is thought to be associated with an increased risk of rupture. Objective To correlate computational fluid dynamic (CFD) indices with bleb formation. Methods Anatomical models were constructed from three-dimensional rotational angiogram (3DRA) data in 27 patients with cerebral aneurysms harbouring single blebs. Additional models representing the aneurysm before bleb formation were constructed by digitally removing the bleb. We characterised haemodynamic features of models both with and without the bleb using CFDs. Flow structure, wall shear stress (WSS), pressure and oscillatory shear index (OSI) were analysed. Results There was a statistically significant association between bleb location at or adjacent to the point of maximal WSS (74.1%, p=0.019), irrespective of rupture status. Aneurysmal blebs were related to the inflow or outflow jet in 88.9% of cases (p<0.001) whilst 11.1% were unrelated. Maximal wall pressure and OSI were not significantly related to bleb location. The bleb region attained a lower WSS following its formation in 96.3% of cases (p<0.001) and was also lower than the average aneurysm WSS in 86% of cases (p<0.001). Conclusion Cerebral aneurysm blebs generally form at or adjacent to the point of maximal WSS and are aligned with major flow structures. Wall pressure and OSI do not contribute to determining bleb location. The measurement of WSS using CFD models may potentially predict bleb formation and thus improve the assessment of rupture risk in unruptured aneurysms.

Specialist nursing training in Poland: Applications for neuroscience nursing

Background: Nurses have a pivotal role in providing, facilitating, advocating and promoting the best possible care and outcome for the client. To ensure decisions and actions are based on current standards of practice, nurses must be accountable for participation in ongoing education in their area of practice. Aim: To present a description of the current state of Polish nursing education and specialized model for neurological and neurosurgical nursing that can be utilized for both undergraduate and postgraduate continuing education in Poland. Data sources: The model of postgraduate training introduced in Poland in 2000 was taken into consideration in developing the framework for neuroscience nursing postgraduate continuing education presented here. The framework for neurological continuing education is also based on a review of the literature and is consistent with Poland’s legally binding professional nursing regulations (normative and implementing regulations). Conclusion: The model demonstrates the need for the content of pre- and post-undergraduate degree education in neurological nursing to be graduated, based on the frameworks for undergraduate education (acquiring the knowledge and basic skills for performing the work of nurses) and postgraduate education (acquiring knowledge and specialist skills necessary for providing advanced nursing care including medical acts on patients with nervous system diseases). Implications for nursing: New and advanced skills gained in specialization training can be applied to complex functions, roles and professional tasks undertaken by nurses in relation to care of patients with neurological dysfunctions.

Deficits on self ordered tasks associated with hyperostosis frontalis interna

A 74 year old patient, EW, with dorsolateral frontal cortical compression due to hyperostosis frontalis interna, in the absence of the Morgagni or Stewart-Morel syndromes, is described. In addition to conventional neuropsychological measures EW was administered one nonspatial and two spatial self ordered working memory tasks, as well as a standard measure of fluid intelligence or g. She showed impaired performance on all three self ordered working memory tasks compared with a normal control group of 10 subjects matched for age, education, sex, and IQ. By contrast, her performance on the fluid intelligence test was comparable with that of the controls. It is concluded that the compression of dorsolateral frontal cortex accompanying hyperostosis frontalis interna may produce selective cognitive impairment.

Diffusion indices on magnetic resonance imaging and neuropsychological performance in amnestic mild cognitive impairment

Background: Magnetic resonance diffusion tensor imaging (DTI) shows promise in the early detection of microstructural pathophysiological changes in the brain. Objectives: To measure microstructural differences in the brains of participants with amnestic mild cognitive impairment (MCI) compared with an age-matched control group using an optimised DTI technique with fully automated image analysis tools and to investigate the correlation between diffusivity measurements and neuropsychological performance scores across groups. Methods: 34 participants (17 participants with MCI, 17 healthy elderly adults) underwent magnetic resonance imaging (MRI)-based DTI. To control for the effects of anatomical variation, diffusion images of all participants were registered to standard anatomical space. Significant statistical differences in diffusivity measurements between the two groups were determined on a pixel-by-pixel basis using gaussian random field theory. Results: Significantly raised mean diffusivity measurements (p<0.001) were observed in the left and right entorhinal cortices (BA28), posterior occipital-parietal cortex (BA18 and BA19), right parietal supramarginal gyrus (BA40) and right frontal precentral gyri (BA4 and BA6) in participants with MCI. With respect to fractional anisotropy, participants with MCI had significantly reduced measurements (p<0.001) in the limbic parahippocampal subgyral white matter, right thalamus and left posterior cingulate. Pearson's correlation coefficients calculated across all participants showed significant correlations between neuropsychological assessment scores and regional measurements of mean diffusivity and fractional anisotropy. Conclusions: DTI-based diffusivity measures may offer a sensitive method of detecting subtle microstructural brain changes associated with preclinical Alzheimer's disease.

Antithrombin III associated with fibrinogen predicts the risk of cerebral ischemic stroke

Background and purpose: The purpose of this study is to examine the feasibility of developing plasma predictive value biomarkers of cerebral ischemic stroke before imaging evidence is acquired. Methods: Blood samples were obtained from 198 patients who attended our neurology department as emergencies - with symptoms of vertigo, numbness, limb weakness, etc. - within 4.5 h of symptom onset, and before imaging evidence was obtained and medical treatment. After the final diagnosis was made by MRI/DWI/MRA or CTA in the following 24-72 h, the above cases were divided into two groups: stroke group and non-stroke group according to the imaging results. The levels of baseline plasma antithrombin III (AT-III), thrombin-antithrombin III (TAT), fibrinogen, D-dimer and high-sensitivity C-reactive protein (hsCRP) in the two groups were assayed. Results: The level of the baseline AT-III in the stroke group was 118.07 ± 26.22%, which was lower than that of the non-stroke group (283.83 ± 38.39%). The levels of TAT, fibrinogen, hsCRP were 7.24 ± 2.28 μg/L, 5.49 ± 0.98 g/L, and 2.17 ± 1.07 mg/L, respectively, which were higher than those of the non-stroke group (2.53 ± 1.23 μg/L, 3.35 ± 0.50 g/L, 1.82 ± 0.67 mg/L). All the P-values were less than 0.001. The D-dimer level was 322.57 ± 60.34 μg/L, which was slightly higher than that of the non-stroke group (305.76 ± 49.52 μg/L), but the P-value was 0.667. The sensitivities of AT-III, TAT, fibrinogen, D-dimer and hsCRP for predicting ischemic stroke tendency were 97.37%, 96.05%, 3.29%, 7.89%, but the specificity was 93.62%, 82.61%, 100% and 100%, respectively, and all the P-values were less than 0.001. High levels of D-dimer and hsCRP were mainly seen in the few cases with severe large-vessel infarction. Conclusions: Clinical manifestations of acute focal neurological deficits were associated with plasma AT-III and fibrinogen. These tests might help the risk assessment of acute cerebral ischemic stroke and/or TIA with infarction tendency in the superacute stage before positive imaging evidence is obtained.

Finite element analysis of vulnerable atherosclerotic plaques: A comparison of mechanical stresses within carotid plaques of acute and recently symptomatic patients with carotid artery disease

Objectives: There is considerable evidence that patients with carotid artery stenosis treated immediately after the ischaemic cerebrovascular event have a better clinical outcome than those who have delayed treatment. Biomechanical assessment of carotid plaques using high-resolution MRI can help examine the relationship between the timing of carotid plaque symptomology and maximum simulated plaque stress concentration. Methods: Fifty patients underwent high-resolution multisequence in vivo MRI of their carotid arteries. Patients with acute symptoms (n=25) underwent MRI within 72 h of the onset of ischaemic cerebrovascular symptoms, whereas recently symptomatic patients (n=25) underwent MRI from 2 to 6 weeks after the onset of symptoms. Stress analysis was performed based on the geometry derived from in vivo MRI of the symptomatic carotid artery at the point of maximum stenosis. The peak stresses within the plaques of the two groups were compared. Results: Patient demographics were comparable for both groups. All the patients in the recently symptomatic group had severe carotid stenosis in contrast to patients with acute symptoms who had predominantly mild to moderate carotid stenosis. The simulated maximum stresses in patients with acute symptoms was significantly higher than in recently symptomatic patients (median (IQR): 313310 4 dynes/cm 2 (295 to 382) vs 2523104 dynes/cm 2 (236 to 311), p=0.02). Conclusions: Patients have extremely unstable, high-risk plaques, with high stresses, immediately after an acute cerebrovascular event, even at lower degrees of carotid stenoses. Biomechanical stress analysis may help us refine our risk-stratification criteria for the management of patients with carotid artery disease in future.

Characterisation of carotid atheroma in symptomatic and asymptomatic patients using high resolution MRI

Background and purpose: To prospectively evaluate differences in carotid plaque characteristics in symptomatic and asymptomatic patients using high resolution MRI. Methods: 20 symptomatic and 20 asymptomatic patients, with at least 50% carotid stenosis as determined by Doppler ultrasound, underwent preoperative in vivo multispectral MRI of the carotid arteries. Studies were analysed both qualitatively and quantitatively in a randomised manner by two experienced readers in consensus, blinded to clinical status, and plaques were classified according to the modified American Heart Association (AHA) criteria. Results: After exclusion of poor quality images, 109 MRI sections in 18 symptomatic and 19 asymptomatic patients were available for analysis. There were no significant differences in mean luminal stenosis severity (72.9% vs 67.6%; p = 0.09) or plaque burden (median plaque areas 50 mm2 vs 50 mm 2; p = 0.858) between the symptomatic and asymptomatic groups. However, symptomatic lesions had a higher incidence of ruptured fibrous caps (36.5% vs 8.7%; p = 0.004), haemorrhage or thrombus (46.5% vs 14.0%; p<0.001), large necrotic lipid cores (63.8% vs 28.0%; p = 0.002) and complicated type VI AHA lesions (61.5% vs 28.1%; p = 0.001) compared with asymptomatic lesions. The MRI findings of plaque haemorrhage or thrombus had an odds ratio of 5.25 (95% CI 2.08 to 13.24) while thin or ruptured fibrous cap (as opposed to a thick fibrous cap) had an odds ratio of 7.94 (95% CI 2.93 to 21.51) for prediction of symptomatic clinical status. Conclusions: There are significant differences in plaque characteristics between symptomatic and asymptomatic carotid atheroma and these can be detected in vivo by high resolution MRI.

Identifying vulnerable carotid plaques in vivo using high resolution magnetic resonance imaging-based finite element analysis

Object. Individuals with carotid atherosclerosis develop symptoms following rupture of vulnerable plaques. Biomechanical stresses within this plaque may increase vulnerability to rupture. In this report the authors describe the use of in vivo carotid plaque imaging and computational mechanics to document the magnitude and distribution of intrinsic plaque stresses. Methods. Ten (five symptomatic and five asymptomatic) individuals underwent plaque characterization magnetic resonance (MR) imaging. Plaque geometry and composition were determined by multisequence review. Intrinsic plaque stress profiles were generated from 3D meshes by using finite element computational analysis. Differences in principal (shear) stress between normal and diseased sections of the carotid artery and between symptomatic and asymptomatic plaques were noted. Results. There was a significant difference in peak principal stress between diseased and nondiseased segments of the artery (mean difference 537.65 kPa, p < 0.05). Symptomatic plaques had higher mean stresses than asymptomatic plaques (627.6 kPa compared with 370.2 kPa, p = 0.05), which were independent of luminal stenosis and plaque composition. Conclusions. Significant differences in plaque stress exist between plaques from symptomatic individuals and those from asymptomatic individuals. The MR imaging-based computational analysis may therefore be a useful aid to identification of vulnerable plaques in vivo.

Correlation of macrophage location and plaque stress distribution using USPIO-enhanced MRI in a patient with symptomatic severe carotid stenosis: A new insight into risk stratification

High resolution, USPIO-enhanced MR imaging can be used to identify inflamed atherosclerotic plaque. We report a case of a 79-year-old man with a symptomatic carotid stenosis of 82%. The plaque was retrieved for histology and finite element analysis (FEA) based on the preoperative MR imaging was used to predict maximal Von Mises stress on the plaque. Macrophage location correlated with maximal predicted stresses on the plaque. This supports the hypothesis that macrophages thin the fibrous cap at points of highest stress, leading to an increased risk of plaque rupture and subsequent stroke.

Inflammation and Complement Activation in Intracranial Artery Aneurysms

Intracranial artery aneurysms (IAs) are estimated to be present in 2.3% of the population. A rupture of an IA causes subarachnoid hemorrhage, with up to 50% mortality. The annual low rupture risk of an IA indicates that most IAs never rupture. The current treatment options are invasive and somewhat risky. Thus rupture-prone IAs should be identified and this requires a better understanding of the IA wall pathobiology. Inflammatory cell infiltrations have been found to precede IA rupture, indicating the role of inflammation in IA wall degeneration and rupture. The complement system is a key mediator of inflammation and house-hold processing of injured tissue. This study aimed at identifying the role of complement activation in IA wall degeneration and the complement activators involved and determining how the complement system is regulated in the IA wall. In immunostainings, the end-product of complement activation, the terminal complement complex (TCC), was located mainly in the outer part of the IA wall, in areas that had also sustained loss of cells. In electron microscopy, the area of maximum TCC accumulation contained cellular debris and evidence of both apoptotic and necrotic cell death. Complement activation correlated with IA wall degeneration and rupture, de-endothelialization, and T-cell and CD163-positive macrophage infiltration. The complement system was found to become activated in all IAs by the classical pathway, with recruitment of alternative pathway amplification. Of the potential activators immunoglobulins G and M and oxidatively modified lipids were found in large areas. Lipid accumulation was observed to clearly colocalize with TCC and C-reactive protein. In the luminal parts of the IA wall, complement activation was limited by cellular expression of protectin (CD59) and extracellular matrix-bound inhibitors, C4b binding protein and factor H whereas the outer part of the wall lacked cells expressing protectin as well as matrix-bound factor H. In single nucleotide polymorphism-analysis, age-related macular degeneration-associated factor H Y402H polymorphism did not associate with the presence of IAs or their rupture The data suggest that complement activation and TCC formation are involved in IA wall degeneration and rupture. Complement seems to become activated by more than one specific activator. The association of complement with de-endothelialization and expression of several complement activators indicate a possible role of endothelial dysfunction and/or impaired clearance mechanisms. Impaired complement regulation seems to be associated with increased complement activation in IA walls. These results stress the role of chronic inflammation in IA wall pathobiology and the regulatory role of complement within this process. Imaging inflammation would possibly enhance the diagnostics of rupture-prone IAs, and targeting IA treatment to prevent chronic inflammation might improve IA treatment in the future.

Microsurgical Aneurysm Model in Rats and Mice: Development of Endovascular Treatment and Optimization of Magnetic Resonance Imaging

The rupture of a cerebral artery aneurysm causes a devastating subarachnoid hemorrhage (SAH), with a mortality of almost 50% during the first month. Each year, 8-11/100 000 people suffer from aneurysmal SAH in Western countries, but the number is twice as high in Finland and Japan. The disease is most common among those of working age, the mean age at rupture being 50-55 years. Unruptured cerebral aneurysms are found in 2-6% of the population, but knowledge about the true risk of rupture is limited. The vast majority of aneurysms should be considered rupture-prone, and treatment for these patients is warranted. Both unruptured and ruptured aneurysms can be treated by either microsurgical clipping or endovascular embolization. In a standard microsurgical procedure, the neck of the aneurysm is closed by a metal clip, sealing off the aneurysm from the circulation. Endovascular embolization is performed by packing the aneurysm from the inside of the vessel lumen with detachable platinum coils. Coiling is associated with slightly lower morbidity and mortality than microsurgery, but the long-term results of microsurgically treated aneurysms are better. Endovascular treatment methods are constantly being developed further in order to achieve better long-term results. New coils and novel embolic agents need to be tested in a variety of animal models before they can be used in humans. In this study, we developed an experimental rat aneurysm model and showed its suitability for testing endovascular devices. We optimized noninvasive MRI sequences at 4.7 Tesla for follow-up of coiled experimental aneurysms and for volumetric measurement of aneurysm neck remnants. We used this model to compare platinum coils with polyglycolic-polylactic acid (PGLA) -coated coils, and showed the benefits of the latter in this model. The experimental aneurysm model and the imaging methods also gave insight into the mechanisms involved in aneurysm formation, and the model can be used in the development of novel imaging techniques. This model is affordable, easily reproducible, reliable, and suitable for MRI follow-up. It is also suitable for endovascular treatment, and it evades spontaneous occlusion.