Martin Wiesmann

S-100 Protein and Neuron-Specific Enolase Concentrations in Blood as Indicators of Infarction Volume and Prognosis in Acute Ischemic Stroke

BACKGROUND AND PURPOSE Better techniques are needed to monitor infarction volume and predict neurological outcome after ischemic brain infarction. We evaluated the usefulness of serial measurements of S-100 protein versus neuron-specific enolase (NSE) in blood samples from patients with acute stroke. METHODS Using nonisotopic sandwich immunoassays, we measured plasma concentrations of S-100 protein and NSE on admission and on days 3, 4, 7, and 14 after infarction in 44 patients (age range, 22 to 86 years; mean age, 65.1 years; 12 female, 32 male). Infarct volume was measured by volumetric CT on day 4 after ictus, and clinical outcome was assessed at discharge from hospital with the Activities of Daily Living Scale and 6 months after infarction with the Glasgow Outcome Scale. RESULTS Peak blood levels of S-100 protein were found on day 2.5 +/- 1.3, and peak levels of NSE were found on day 1.9 +/- 0.8 after infarction. Peak plasma levels of S-100 protein correlated well with infarct volume (r = .75, P < .001) and with clinical outcome assessed with the Glasgow Outcome Scale (r = .51, P < .001). Serum levels of NSE correlated with infarct volume (r = .37, P < .05) but not with clinical outcome (r = .18, P > .05). CONCLUSIONS The results of our study indicate that measuring blood concentrations of S-100 protein periodically in the first 10 days after cerebral infarction helps to predict infarct volume and the long-term neurological outcome more accurately than periodic measurements of blood concentrations of NSE.

Brain activation patterns during imagined stance and locomotion in functional magnetic resonance imaging

Posture and gait are sensorimotor actions that involve peripheral, spinal, and supraspinal structures. To investigate brain activity during stance and locomotion, 13 healthy subjects were asked to stand, walk, run, and lie down; subsequently, they were trained to imagine standing, walking, running, and lying [imagined lying as rest condition in functional magnetic resonance imaging (fMRI)]. Separate and distinct activation/deactivation patterns were found for the three imagined conditions: (1) standing imagery was associated with activation in the thalamus, basal ganglia, and cerebellar vermis; (2) walking imagery was associated with activation in the parahippocampal and fusiform gyri (areas involved in visuospatial navigation), occipital visual areas, and in the cerebellum; (3) running imagery caused a predominantly cerebellar activation in the vermis and adjacent hemispheres (six times larger than during imagination of walking or standing), but activations in the parahippocampal and fusiform gyri were smaller than during walking. Deactivations were found for walking and running, but not for standing imagery. They were located in the vestibular (posterior insula, superior temporal gyrus, supramarginal gyrus) and somatosensory (postcentral gyrus) cortex with right-hemispheric dominance. These findings support the concept of a hierarchical organization of posture and locomotion. Automated locomotion, for example, running, is based on spinal generators whose pace is driven by the cerebellar locomotor region. Deactivation in the vestibular and somatosensory cortex prevents adverse interactions with the optimized spinal pattern and sensory signals; this confirms earlier findings of a multisensory inhibition during unhindered locomotion. During slow walking, spatial navigation, mediated by the parahippocampal cortex, becomes more important. Postural control during standing involves a low intensity cerebellar activity and sensorimotor control via the thalamus and basal ganglia.

Reduced perception of bodily signals in anorexia nervosa

OBJECTIVE Interoceptive awareness is known to be impaired in eating disorders. To date, it has remained unclear whether this variable is related to the construct of interoceptive sensitivity. Interoceptive sensitivity is considered to be an essential variable in emotional processes. The objective of the study was to elucidate this potential relationship and to clarify whether general interoceptive sensitivity is reduced in anorexia nervosa. METHODS Using a heartbeat perception task, interoceptive sensitivity was assessed in 28 female patients with anorexia nervosa and 28 matched healthy controls. Questionnaires assessing interoceptive awareness (EDI) and several other variables were also administered. RESULTS Patients with anorexia nervosa displayed significantly decreased interoceptive sensitivity. They also had more difficulties in interoceptive awareness. CONCLUSIONS In addition to a decreased ability to recognize certain visceral sensations related to hunger, there is a generally reduced capacity to accurately perceive bodily signals in anorexia nervosa. This highlights the potential importance of interoceptive sensitivity in the pathogenesis of eating disorders.

Imaging human supraspinal locomotor centers in brainstem and cerebellum

An erect posture with bipedal locomotion is a characteristic feature of humans compared to other mammals. Most of our knowledge about the hierarchical network of supraspinal locomotor centers derives from animal experiments, mainly in the cat. We posed the question of whether evolutionary transition from quadrupedal to bipedal locomotion--with associated change of foreleg function--caused reorganization of these supraspinal locomotor centers. Using functional magnetic resonance imaging, we identified separate and distinct cerebellar and brainstem BOLD signal increases related to posture and gait during mental imagery of standing, walking, and running in healthy volunteers (n=26). Comparison with the locomotion centers in the cat showed that these activations include the pacemakers for gait initiation and speed regulation in the interfastigial cerebellum and bilateral midbrain tegmentum (cerebellar and mesencephalic locomotor regions), their descending target regions in the pontine reticular formation, and the rhythm generators in the cerebellar vermis and paravermal cortex. Moreover, during mental imagery of stance, a BOLD signal increase was observed in the dorsal pons, reflecting an activation of the dorsal tegmental field, a locomotion-suppressing site in the cat. These results support the view that the organization of supraspinal locomotor centers was preserved during the transition to bipedal locomotion. The clinical relevance of these centers has so far been largely neglected. However, Parkinsons disease, for example, is associated with reduced cell counts in the pedunculopontine nucleus, a part of the mesencephalic locomotor region. This association suggests that deep brain stimulation of locomotion centers may provide new therapeutic approaches for common gait disorders.

Functional MRI of galvanic vestibular stimulation with alternating currents at different frequencies.

Functional MRI was performed in 28 healthy volunteers to study the effects of galvanic vestibular stimulation with alternating currents (AC-GVS) of different frequencies on brain activation patterns. The aims of this study were (1) to identify specific areas within the vestibular cortical network that are involved in the processing of frequency-specific aspects by correlation analyses, (2) to determine the optimal frequency for stimulation of the vestibular system with respect to perception, and (3) to analyze whether different frequencies of AC-GVS are mediated in different cortical areas or different sites within the vestibular cortex. AC-GVS was performed using sinusoidal stimulation currents with an amplitude of +/-2.5 mA, and frequencies of 0.1 Hz, 0.3 Hz, 0.8 Hz, 1.0 Hz, 2.0 Hz, and 5.0 Hz were applied. Regardless of the applied stimulation frequency, AC-GVS elicited activations within a network of multisensory areas similar to those described in earlier studies using direct currents. No mapping of different stimulation frequencies to different cortical locations was observed. Additional activations of somatosensory cortex areas were observed during stimulation with 5 Hz only. The strongest vestibular sensations were reported during stimulation with 1 Hz and 2 Hz. Correlation analyses between blood oxygenation level dependent (BOLD) signal changes and stimulation frequency revealed a positive dependency in areas of the supramarginal gyrus, posterolateral thalamus, cerebellar vermis, posterior insula, and in the hippocampal region/uncus. These regions represent areas involved in the processing of vestibular information for head and body orientation in space.

S-100 protein plasma levels after aneurysmal subarachnoid haemorrhage

SummaryWe investigated the level of S-100 protein in blood as an indicator of brain damage in 71 patients suffering from subarachnoid haemorrhage (SAH) due to ruptured aneurysms.Concentrations of S-100 protein were determined by micro-titre based immunofluorometic assay detecting predominantly S-100b on blood samples obtained 24 hours, 3 days and 7 days after onset of symptoms in patients with SAH and from 120 healthy control subjects. Neurological status was assessed using the Hunt and Hess (HH) scale on admission and by the Glasgow Outcome Scale (GOS) 6 months later.Mean concentrations of S-100 protein in blood were significantly (p<0.0001) higher in patients 24 hours (0.263±0.387 μg/l), 3 days (0.192±0.288 μg/l) and 7 days (0.256±0.442 μg/l) after onset of SAH symptoms compared to controls (0.050±0.081 μg/l). More severe neurological symptoms (higher HH scale scores) on admission correlated with higher S-100 levels on admission (R=0.70) and Day 3 (R=0.66) (p<0.0001). Worse outcome (lower GOS score) 6 months after SAH was also associated with higher plasma concentration of S-100 in the first week after SAH.In summary, this study showed that in patients with SAH due to ruptured aneurysm, S-100 protein levels correlate with early neurological deficit and are as sensitive as HH scores in predicting neurological outcome (GOS scores). Measurement of S-100 protein in blood is a reliable non-invasive method and may be clinically useful to screen for and monitor progression of central nervous system diseases of various origins.

Functional Connectivity Bias of the Orbitofrontal Cortex in Drug-Free Patients with Major Depression

BACKGROUND The orbitofrontal cortex (OFC) plays a crucial role in emotion-processing circuits and should therefore also be included in models of the pathophysiology of major depression. The aim of this study was to compare the functional connectivity of the OFC during emotion processing in patients with major depression and healthy control subjects. METHODS Twenty-five untreated patients with major depression and 15 healthy control subjects were investigated using a functional magnetic resonance imaging face-matching task. RESULTS Dorsal anterior cingulate cortex, precuneus, and cerebellum activity showed less connectivity with the OFC in patients than in control subjects. In contrast, functional connectivity between the OFC and the right dorsolateral prefrontal cortex (DLPFC), right inferior frontal operculum, and left motor areas was increased in patients compared with healthy control subjects. CONCLUSIONS The OFC plays a key role in the pathophysiology of major depression. The observed imbalance of OFC connectivity seems to represent a neural mechanism of the processing bias. From a neurobiological point of view, the uncoupling of precuneus and gyrus cinguli activity from the OFC might be associated with problems in the regulation of self-schemas, whereas the increased connectivity of the DLPFC to the OFC might represent a higher neural response to negative stimuli.

Subarachnoid Hemosiderosis and Superficial Cortical Hemosiderosis in Cerebral Amyloid Angiopathy

SUMMARY: Cerebral amyloid angiopathy (CAA) is an important cause of intracerebral hemorrhage. Its definite diagnosis still requires histopathologic demonstration of vascular amyloid. Thus, further improvement of noninvasive imaging methods would be desirable. Here we present 3 patients with histologically proved CAA, in which superficial cortical hemosiderosis and subarachnoid hemosiderosis were present in T2*-weighted MR images. Thus, we propose that these 2 findings might be valuable as noninvasive diagnostic markers for CAA.

Elevated plasma Levels of S-100b protein in schizophrenic patients

BACKGROUND In this study, we examined the possibility that structural damage to the brain may play a role in the pathogenesis of schizophrenia. METHODS We compared plasma levels of S-100b protein in 20 patients with schizophrenic psychosis and 20 age- and gender-matched healthy blood donors. Concentrations of S-100 protein were determined by microtiter-based immunofluorometric assay detecting predominantly S-100b. RESULTS Mean concentrations of S-100b protein in blood were significantly (p < or = .001) higher in schizophrenic patients (0.165 +/- 0.138 microgram/L) compared to control subjects (0.054 +/- 0.031 microgram/L). Levels did not correlate with age of onset or duration of psychosis. CONCLUSIONS Our findings indicate that patients with schizophrenia may suffer ongoing structural damage to cells of the central nervous system, and that the concentration of S-100b protein in plasma may help to identify clinical subgroups in schizophrenia.

Visualization of cranial nerves I-XII: value of 3D CISS and T2-weighted FSE sequences

Abstract. The aim of this study was to evaluate the sensitivity of the three-dimensional constructive interference of steady state (3D CISS) sequence (slice thickness 0.7 mm) and that of the T2-weighted fast spin echo (T2-weighted FSE) sequence (slice thickness 3 mm) for the visualization of all cranial nerves in their cisternal course. Twenty healthy volunteers were examined using the T2-weighted FSE and the 3D CISS sequences. Three observers evaluated independently the cranial nerves NI–NXII in their cisternal course. The rates for successful visualization of each nerve for 3D CISS (and for T2-weighted FSE in parentheses) were as follows: NI, NII, NV, NVII, NVIII 40 of 40 (40 of 40), NIII 40 of 40 (18 of 40), NIV 19 of 40 (3 of 40), NVI 39 of 40 (5 of 40), NIX, X, XI 40 of 40 (29 of 40), and NXII 40 of 40 (4 of 40). Most of the cranial nerves can be reliably assessed when using the 3D CISS and the T2-weighted FSE sequences. Increasing the spatial resolution when using the 3D CISS sequence increases the reliability of the identification of the cranial nerves NIII–NXII.