Endovascular treatment for acute ischemic stroke patients: implications and interpretation of IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials: A report from the Working Group of International Congress of Interventional Neurology

OBJECTIVE The results of Interventional Management of Stroke (IMS) III, Magnetic Resonance and REcanalization of Stroke Clots Using Embolectomy (MR RESCUE), and SYNTHESIS EXPANSION trials are expected to affect the practice of endovascular treatment for acute ischemic stroke. The purpose of this report is to review the components of the designs and methods of these trials and to describe the influence of those components on the interpretation of trial results. METHODS A critical review of trial design and conduct of IMS III, MR RESCUE, and SYNTHESIS EXPANSION is performed with emphasis on patient selection, shortcomings in procedural aspects, and methodology of data ascertainment and analysis. The influence of each component is estimated based on published literature including multicenter clinical trials reporting on endovascular treatment for acute ischemic stroke and myocardial infarction. RESULTS We critically examined the time interval between symptom onset and treatment and rates of angiographic recanalization to differentiate between "endovascular treatment" and "parameter optimized endovascular treatment" as it relates to the IMS III, MR RESCUE, and SYNTHESIS EXPANSION trials. All the three trials failed to effectively test "parameter optimized endovascular treatment" due to the delay between symptom onset and treatment and less than optimal rates of recanalization. In all the three trials, the magnitude of benefit with endovascular treatment required to reject the null hypothesis was larger than could be expected based on previous studies. The IMS III and SYNTHESIS EXPANSION trials demonstrated that rates of symptomatic intracerebral hemorrhages subsequent to treatment are similar between IV thrombolytics and endovascular treatment in matched acute ischemic stroke patients. The trials also indirectly validated the superiority/equivalence of IV thrombolytics (compared with endovascular treatment) in patients with minor neurological deficits and those without large vessel occlusion on computed tomographic/magnetic resonance angiography. CONCLUSIONS The results do not support a large magnitude benefit of endovascular treatment in subjects randomized in all the three trials. The possibility that benefits of a smaller magnitude exist in certain patient populations cannot be excluded. Large magnitude benefits can be expected with implementation of "parameter optimized endovascular treatment" in patients with ischemic stroke who are candidates for IV thrombolytics.

A review of clinical trial designs used to detect a disease-modifying effect of drug therapy in Alzheimer's disease and Parkinson's disease

Acknowledgements This article presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0707-10124). The views expressed in this article are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The funders had no role in study design, data collection, data analysis, data interpretation, writing of the report or for the decision to submit for publication.

Clinical prediction of large vessel occlusion in anterior circulation stroke: mission impossible?

Simple clinical scores to predict large vessel occlusion (LVO) in acute ischemic stroke would be helpful to triage patients in the prehospital phase. We assessed the ability of various combinations of National Institutes of Health Stroke Scale (NIHSS) subitems and published stroke scales (i.e., RACE scale, 3I-SS, sNIHSS-8, sNIHSS-5, sNIHSS-1, mNIHSS, a-NIHSS items profiles A-E, CPSS1, CPSS2, and CPSSS) to predict LVO on CT or MR arteriography in 1085 consecutive patients (39.4 % women, mean age 67.7 years) with anterior circulation strokes within 6 h of symptom onset. 657 patients (61 %) had an occlusion of the internal carotid artery or the M1/M2 segment of the middle cerebral artery. Best cut-off value of the total NIHSS score to predict LVO was 7 (PPV 84.2 %, sensitivity 81.0 %, specificity 76.6 %, NPV 72.4 %, ACC 79.3 %). Receiver operating characteristic curves of various combinations of NIHSS subitems and published scores were equally or less predictive to show LVO than the total NIHSS score. At intersection of sensitivity and specificity curves in all scores, at least 1/5 of patients with LVO were missed. Best odds ratios for LVO among NIHSS subitems were best gaze (9.6, 95 %-CI 6.765-13.632), visual fields (7.0, 95 %-CI 3.981-12.370), motor arms (7.6, 95 %-CI 5.589-10.204), and aphasia/neglect (7.1, 95 %-CI 5.352-9.492). There is a significant correlation between clinical scores based on the NIHSS score and LVO on arteriography. However, if clinically relevant thresholds are applied to the scores, a sizable number of LVOs are missed. Therefore, clinical scores cannot replace vessel imaging.

Neuromarketing and consumer neuroscience:contributions to neurology

Background: 'Neuromarketing' is a term that has often been used in the media in recent years. These public discussions have generally centered around potential ethical aspects and the public fear of negative consequences for society in general, and consumers in particular. However, positive contributions to the scientific discourse from developing a biological model that tries to explain context-situated human behavior such as consumption have often been neglected. We argue for a differentiated terminology, naming commercial applications of neuroscientific methods 'neuromarketing' and scientific ones 'consumer neuroscience'. While marketing scholars have eagerly integrated neuroscientific evidence into their theoretical framework, neurology has only recently started to draw its attention to the results of consumer neuroscience.Discussion: In this paper we address key research topics of consumer neuroscience that we think are of interest for neurologists; namely the reward system, trust and ethical issues. We argue that there are overlapping research topics in neurology and consumer neuroscience where both sides can profit from collaboration. Further, neurologists joining the public discussion of ethical issues surrounding neuromarketing and consumer neuroscience could contribute standards and experience gained in clinical research.Summary: We identify the following areas where consumer neuroscience could contribute to the field of neurology:. First, studies using game paradigms could help to gain further insights into the underlying pathophysiology of pathological gambling in Parkinson's disease, frontotemporal dementia, epilepsy, and Huntington's disease.Second, we identify compulsive buying as a common interest in neurology and consumer neuroscience. Paradigms commonly used in consumer neuroscience could be applied to patients suffering from Parkinson's disease and frontotemporal dementia to advance knowledge of this important behavioral symptom.Third, trust research in the medical context lacks empirical behavioral and neuroscientific evidence. Neurologists entering this field of research could profit from the extensive knowledge of the biological foundation of trust that scientists in economically-orientated neurosciences have gained.Fourth, neurologists could contribute significantly to the ethical debate about invasive methods in neuromarketing and consumer neuroscience. Further, neurologists should investigate biological and behavioral reactions of neurological patients to marketing and advertising measures, as they could show special consumer vulnerability and be subject to target marketing. © 2013 Javor et al.; licensee BioMed Central Ltd.

Philosophy's loss, neurology's gain:the endeavor of John Hughlings-Jackson

The year 2011 marked the centenary of the death of one of the founders of British neurology, John Hughlings-Jackson (1835-1911). By common consent he was a great clinician. But he was more. He endeavored to use clinical observations to throw light on one of the great problems of the modern world, the problem of mind. Hughlings-Jackson's daily contact with mentalities warped by neurological disease caused him to ponder deeply the nature of the mind-brain relationship, nowadays often known simply as the "hard problem. " In particular, he saw the danger of conflating mind and brain, a danger that has grown greater with the spectacular growth of neuroscientific knowledge during the last century. Although Hughlings-Jackson's neuroscientific thought is long outdated, his philosophic endeavors remain highly instructive. © 2012 by The Johns Hopkins University Press.

Clinical characteristics of patients with epilepsy in a specialist neuropsychiatry service

Neuropsychiatry services provide specialist input into the assessment and management of behavioral symptoms associated with a range of neurological conditions, including epilepsy. Despite the centrality of epilepsy to neuropsychiatry and the recent expansion of neuropsychiatry service provision, little is known about the clinical characteristics of patients with epilepsy who are routinely seen by a specialist neuropsychiatry service. This retrospective study filled this gap by retrospectively evaluating a naturalistic series of 60 consecutive patients with epilepsy referred to and assessed within a neuropsychiatry setting. Fifty-two patients (86.7%) had active epilepsy and were under the ongoing care of the referring neurologist for seizure management. The majority of patients (N = 42; 70.0%) had a diagnosis of localization-related epilepsy, with temporal lobe epilepsy as the most common epilepsy type (N = 37; 61.7%). Following clinical assessment, 39 patients (65.0%) fulfilled formal diagnostic criteria for at least one psychiatric disorder; nonepileptic attack disorder (N = 37; 61.7%), major depression (N = 23; 38.3%), and generalized anxiety disorder (N = 16; 26.7%) were the most commonly diagnosed comorbidities. The clinical characteristics of patients seen in specialist neuropsychiatry settings are in line with the results from previous studies in neurology clinics in terms of both epilepsy and psychiatric comorbidity. Our findings confirm the need for the development and implementation of structured care pathways for the neuropsychiatric aspects of epilepsy, with focus on comorbid nonepileptic attacks and affective and anxiety symptoms. This is of particular importance in consideration of the impact of behavioral symptoms on patients' health-related quality of life.

Clinical Accuracy of the MedGem Indirect Calorimeter for Measuring Resting Energy Expenditure in Cancer Patients

OBJECTIVE: To compare, in patients with cancer and in healthy subjects, measured resting energy expenditure (REE) from traditional indirect calorimetry to a new portable device (MedGem) and predicted REE. DESIGN: Cross-sectional clinical validation study. SETTING: Private radiation oncology centre, Brisbane, Australia. SUBJECTS: Cancer patients (n = 18) and healthy subjects (n = 17) aged 37-86 y, with body mass indices ranging from 18 to 42 kg/m(2). INTERVENTIONS: Oxygen consumption (VO(2)) and REE were measured by VMax229 (VM) and MedGem (MG) indirect calorimeters in random order after a 12-h fast and 30-min rest. REE was also calculated from the MG without adjustment for nitrogen excretion (MGN) and estimated from Harris-Benedict prediction equations. Data were analysed using the Bland and Altman approach, based on a clinically acceptable difference between methods of 5%. RESULTS: The mean bias (MGN-VM) was 10% and limits of agreement were -42 to 21% for cancer patients; mean bias -5% with limits of -45 to 35% for healthy subjects. Less than half of the cancer patients (n = 7, 46.7%) and only a third (n = 5, 33.3%) of healthy subjects had measured REE by MGN within clinically acceptable limits of VM. Predicted REE showed a mean bias (HB-VM) of -5% for cancer patients and 4% for healthy subjects, with limits of agreement of -30 to 20% and -27 to 34%, respectively. CONCLUSIONS: Limits of agreement for the MG and Harris Benedict equations compared to traditional indirect calorimetry were similar but wide, indicating poor clinical accuracy for determining the REE of individual cancer patients and healthy subjects.

The STRATIFY tool and clinical judgment were poor predictors of falling in an acute hospital setting

Objective: To compare the effectiveness of the STRATIFY falls tool with nurses’ clinical judgments in predicting patient falls. Study Design and Setting: A prospective cohort study was conducted among the inpatients of an acute tertiary hospital. Participants were patients over 65 years of age admitted to any hospital unit. Sensitivity, specificity, and positive predictive value (PPV) and negative predictive values (NPV) of the instrument and nurses’ clinical judgments in predicting falls were calculated. Results: Seven hundred and eighty-eight patients were screened and followed up during the study period. The fall prevalence was 9.2%. Of the 335 patients classified as being ‘‘at risk’’ for falling using the STRATIFY tool, 59 (17.6%) did sustain a fall (sensitivity50.82, specificity50.61, PPV50.18, NPV50.97). Nurses judged that 501 patients were at risk of falling and, of these, 60 (12.0%) fell (sensitivity50.84, specificity50.38, PPV50.12, NPV50.96). The STRATIFY tool correctly identified significantly more patients as either fallers or nonfallers than the nurses (P50.027). Conclusion: Considering the poor specificity and high rates of false-positive results for both the STRATIFY tool and nurses’ clinical judgments, we conclude that neither of these approaches are useful for screening of falls in acute hospital settings.

Attention and memory bias for body image and health related information using an Emotional Stroop task in a non-clinical sample

It has been proposed that body image disturbance is a form of cognitive bias wherein schemas for self-relevant information guide the selective processing of appearancerelated information in the environment. This threatening information receives disproportionately more attention and memory, as measured by an Emotional Stroop and incidental recall task. The aim of this thesis was to expand the literature on cognitive processing biases in non-clinical males and females by incorporating a number of significant methodological refinements. To achieve this aim, three phases of research were conducted. The initial two phases of research provided preliminary data to inform the development of the main study. Phase One was a qualitative exploration of body image concerns amongst males and females recruited through the general community and from a university. Seventeen participants (eight male; nine female) provided information on their body image and what factors they saw as positively and negatively impacting on their self evaluations. The importance of self esteem, mood, health and fitness, and recognition of the social ideal were identified as key themes. These themes were incorporated as psycho-social measures and Stroop word stimuli in subsequent phases of the research. Phase Two involved the selection and testing of stimuli to be used in the Emotional Stroop task. Six experimental categories of words were developed that reflected a broad range of health and body image concerns for males and females. These categories were high and low calorie food words, positive and negative appearance words, negative emotion words, and physical activity words. Phase Three addressed the central aim of the project by examining cognitive biases for body image information in empirically defined sub-groups. A National sample of males (N = 55) and females (N = 144), recruited from the general community and universities, completed an Emotional Stroop task, incidental memory test, and a collection of psycho-social questionnaires. Sub-groups of body image disturbance were sought using a cluster analysis, which identified three sub-groups in males (Normal, Dissatisfied, and Athletic) and four sub-groups in females (Normal, Health Conscious, Dissatisfied, and Symptomatic). No differences were noted between the groups in selective attention, although time taken to colour name the words was associated with some of the psycho-social variables. Memory biases found across the whole sample for negative emotion, low calorie food, and negative appearance words were interpreted as reflecting the current focus on health and stigma against being unattractive. Collectively these results have expanded our understanding of processing biases in the general community by demonstrating that the processing biases are found within non-clinical samples and that not all processing biases are associated with negative functionality