The anatomy of spatial neglect based on voxelwise statistical analysis: a study of 140 patients

A major challenge for any anatomical study of spatial neglect in neurological patients is that human lesions vary tremendously in extent and location between individuals. Approaches to this problem used in previous studies were to focus on subgroups of patients that are more homogeneous either with respect to the branch territory affected by the stroke or with respect to existing additional neurological symptoms (e.g. additional visual field defects). It could be argued that such strategies might bias the conclusions on the critical substrate associated with spatial neglect. The present study thus addressed the high variability inherent in naturally occurring lesions by using an unselected, but very large sample size and by comparing a neglect group with a non-neglect group using voxelwise statistical testing. We investigated an unselected 7 year sample of 140 consecutively admitted patients with right hemisphere strokes. Seventy-eight had spatial neglect, 62 did not show the disorder. The incidence of visual field defects was comparable in both groups. For assessing lesion location, in a first step, we used conventional lesion density plots together with subtraction analysis. Moreover, due to the large size of the sample voxelwise statistical testing was possible to objectively estimate which brain regions are more frequently compromised in neglect patients relative to patients without neglect. The results demonstrate that the right superior temporal cortex, the insula and subcortically putamen and caudate nucleus are the neural structures damaged significantly more often in patients with spatial neglect.     

Preoperative cardiac risk assessment

Heart disease is the leading cause of mortality in the United States. An important subset of heart disease is perioperative myocardial infarction, which affects approximately 50,000 persons each year. The American College of Cardiology (ACC) and American Heart Association (AHA) have coauthored a guideline on preoperative cardiac risk assessment, as has the American College of Physicians (ACP). The ACC/AHA guideline uses major, intermediate, and minor clinical predictors to stratify patients into different cardiac risk categories. Patients with poor functional status or those undergoing high-risk surgery require further risk stratification via cardiac stress testing. The ACP guideline also starts by screening patients for clinical variables that predict perioperative cardiac complications. However, the ACP did not feel there was enough evidence to support poor functional status as a significant predictor of increased risk. High-risk patients would sometimes merit preoperative cardiac catheterization by the ACC/AHA guideline, while the ACP version would reserve catheterization only for those who were candidates for cardiac revascularization independent of their noncardiac surgery. A recent development in prophylaxis of surgery-related cardiac complications is the use of beta blockers perioperatively for patients with cardiac risk factors.     

Shutter-glasses haploscope with eye-tracking control for fusion therapy

BACKGROUND: Common haploscopes require a manual input of the presented disparity and particularly prepared images; moreover, they can be used predominantly by orthoptists. We developed a device that makes possible a haploscope on the basis of a computer monitor with shutter-glasses. The presented disparity is determined with help of an eye-tracker. MATERIALS AND METHODS: A patient looks at a monitor through shutter-glasses, the eyes being recorded by a camera. An eye-tracking software determines the fixation points and the angle of strabismus. Images are presented at the monitor with a disparity that is regulated according to these measurements. This is controlled by means of a software so that the disparity is gradually decreased according to the patients abilities. Diagnostic data are recorded permanently. RESULTS: Any monitor contents, such as videos, TV or computer applications, can be used for fusion training or diagnostic purposes with the new apparatus. Initial investigations of patients with heterophoria or intermittent exophoria indicate a decrease of the subjective angle of strabismus by compensation and an increase of the fusional range. CONCLUSIONS: The developed shutter-glass-haploscope with eye-tracking control provides several methods for diagnosis. The appliance provides automated fusion training adapted to the patient that can be done at the working place or at home.     

The cortical substrate of visual extinction

Neuroimaging studies investigated the attentional systems of the human brain revealing two networks, one for voluntary allocation of attention and another for stimulus-driven attentional processes. Whereas lesions of the latter system were supposed to lead to spatial neglect, we show that such lesions rather are typical for the occurrence of visual extinction. Extinction describes the inability of brain-damaged patients to detect a contralesional target in the presence of a competing ipsilesional stimulus. In a sample of consecutively admitted patients with right hemisphere stroke, we found dissociable cortical substrates for spatial neglect and visual extinction. There was a surprising congruency between the typical lesion site in patients with extinction and the activation clusters found in previous neuroimaging studies of healthy subjects. The results show that the temporo-parietal junction (TPJ), considered to be a crucial part of the stimulus-driven attentional network, is the neural substrate of visual extinction.     

Severity of neglect predicts accuracy of imitation in patients with right hemisphere lesions

Goldenberg [Goldenberg, G. (1996). Defective imitation of gestures in patients with damage in the left or right hemisphere. Journal of Neurology, Neurosurgery, and Psychiatry, 61, 176–180] proposed that the vulnerability of the imitation of meaningless gestures to right or left brain damage depends on the body parts that are involved in the gestures. Whereas imitation of hand postures was disturbed only in patients with left brain damage, imitation of finger postures was affected to similar degrees in left and right brain damage. Subsequent studies confirmed the selective vulnerability of hand postures to LBD but failed to replicate the severe disturbance of finger postures in RBD. In contrast to Goldenberg's studies, these studies excluded RBD patients with neglect. The present investigation aimed to explore the relationship between spatial neglect and imitation of finger postures in RBD patients.Presence and severity of spatial neglect and accuracy of imitation of hand and finger postures were tested in 50 RBD patients. Disturbance of imitation was much more severe for finger than hand postures and was tightly correlated with severity of neglect. The number of errors was higher for fingers which from the patient's perspective were located on the left side of the examiner's demonstrating hand but this spatial bias was not sufficient to explain all errors. Possible causes for non-lateralized errors could be a general narrowing of the focus of attention and reduced capacity for processing of visual information which have been postulated to be regular companions of the lateral displacement of attention in spatial neglect.     

Identification of the protein receptor binding site of botulinum neurotoxins B and G proves the double-receptor concept

Botulinum neurotoxins (BoNTs) cause muscle paralysis by selectively cleaving core components of the vesicular fusion machinery within motoneurons. Complex gangliosides initially bind into a pocket that is conserved among the seven BoNTs and tetanus neurotoxin. Productive neurotoxin uptake also requires protein receptors. The interaction site of the protein receptor within the neurotoxin is currently unknown. We report the identification and characterization of the protein receptor binding site of BoNT/B and BoNT/G. Their protein receptors, synaptotagmins I and II, bind to a pocket at the tip of their H(CC) (C-terminal domain of the C-terminal fragment of the heavy chain) that corresponds to the unique second carbohydrate binding site of tetanus neurotoxin, the sialic acid binding site. Substitution of amino acids in this region impaired binding to synaptotagmins and drastically decreased toxicity at mouse phrenic nerve preparations; CD-spectroscopic analyses evidenced that the secondary structure of the mutated neurotoxins was unaltered. Deactivation of the synaptotagmin binding site by single mutations led to virtually inactive BoNT/B and BoNT/G when assayed at phrenic nerve preparations of complex-ganglioside-deficient mice. Analogously, a BoNT B mutant with deactivated ganglioside and synaptotagmin binding sites lacked appreciable activity at wild-type mouse phrenic nerve preparations. Thus, these data exclude relevant contributions of any cell surface molecule other than one ganglioside and one protein receptor to the entry process of BoNTs, which substantiates the double-receptor concept. The molecular characterization of the synaptotagmin binding site provides the basis for designing a novel class of potent binding inhibitors.