An unusual location of deep venous thrombosis associated with ischemic stroke and persistent foramen ovale.

Up to 40% of ischemic strokes have no known cause (cryptogenic). The prevalence of persistent foramen ovale (PFO) amongst patients with cryptogenic stroke (CS) is twice as high as that of the normal population, therefore suggesting a causal relationship between the two entities. However, PFO by itself is not sufficient to cause stroke, as an embolic source is needed. This source is often unknown, making the causal relationship between CS and PFO hard to demonstrate. The most frequent, although still seldom, identifiable cause of embolism in an otherwise cryptogenic stroke associated with PFO is a deep venous thrombosis (DVT) of the lower extremities. Here, we present a unique case of brachiocephalic venous DVT associated with PFO and ischemic stroke in a young patient. As the search for DVT in patients with PFO and stroke is often limited to the lower extremities, this case may suggest that an unspecified number of DVTs are overlooked. Our report lends support to paradoxical embolism as a mechanism of stroke in patients with PFO and does, at least in selected cases, suggest a more detailed search for DVT beyond the lower extremities.

A novel clinical syndrome revealing a deficiency of the muscarinic M3 receptor.

OBJECTIVES: No clinical disorders have been caused by dysfunction of any of the 5 subtypes (M1-M5) of muscarinic receptors. We present a patient with a novel clinical syndrome that we suggest results from a deficiency of the muscarinic M3 receptor. METHODS: We conducted a comprehensive workup of autonomic function. The patient's disorder was compared to the phenotypic features of male M3 knockout mice. M3 protein quantity was assessed by Western blot and radioligand binding in peripheral blood lymphocytes. Tests for autoantibodies and genetic abnormalities were performed. RESULTS: The disease pattern was characterized by disturbances in micturition, pupil constriction, body weight, and sudomotor function, with normal accommodation, gastrointestinal motility, salivation, and lacrimation, similar to features of male M3 knockout mice. M3 protein quantity was reduced. Genetic tests were unrevealing, but unspecific antinuclear antibodies were present. CONCLUSIONS: The presented clinical syndrome suggests a deficiency of the muscarinic M3 receptor. These results and future evaluation of patients with autonomic deficits may provide insights into the site and functional role of the muscarinic M3 receptor in humans.

Normal spatial attention but impaired saccades and visual motion perception after lesions of the monkey cerebellum.

Lesions of the cerebellum produce deficits in movement and motor learning. Saccadic dysmetria, for example, is caused by lesions of the posterior cerebellar vermis. Monkeys and patients with such lesions are unable to modify the amplitude of saccades. Some have suggested that the effects on eye movements might reflect a more global cognitive deficit caused by the cerebellar lesion. We tested that idea by studying the effects of vermis lesions on attention as well as saccadic eye movements, visual motion perception, and luminance change detection. Lesions in posterior vermis of four monkeys caused the known deficits in saccadic control. Attention tested by examination of acuity threshold changes induced by prior cueing of the location of the targets remained normal after vermis lesions. Luminance change detection was also unaffected by the lesions. In one case, after a lesion restricted to lobulus VIII, the animal had impaired visual motion perception.

[Practical examinations for neurology. The Tuebingen model]. / Praktische Prüfungen in der Neurologie. Das Tübinger Modell.

Practically orientated examinations represent an important innovation in medical education. In the subject area of neurology, the "Objective Structured Clinical Examination" (OSCE) proved to be a viable form of examination for the subject of neurological anamnesis and a medical examination course at the University of Tuebingen in Germany. A total of 577 students in their sixth semester of study were examined in, to date, four OSCEs and achieved an average of 17.5 of possible 25 points in the subject of neurology. Improvement in point average was observable over the course of time, while the average performance of students across the total OSCE remained constant. Student evaluations regarding form and content of the neurological examinations yielded an average grade of B (in the German system 2.1). Simulation patients were rated with an average grade of A- (German system 1.7). Examination methods are presented together with experience concerning preparation, implementation, and developmental enhancement of neurological OSCE examinations. Implications of this novel form of examination for faculty development and regulating students' learning and study behaviour are discussed.

Second primary tumor in anti-Ma1/2-positive paraneoplastic limbic encephalitis.

Memory loss can be a symptom of paraneoplastic limbic encephalitis (PLE) a neuropsychiatric disorder associated mostly with small-cell lung cancer and anti-Hu antibodies or with testicular tumors and anti-Ma2 antibodies. We present the case of a patient with temporal coincidence of beginning cognitive decline and diagnosis of a carcinoma of the prostate in whom we diagnosed anti-Ma1/Ma2-positive PLE. The tumor had been completely resected but memory impairment further deteriorated. As the effective treatment of the cancer is considered as the most efficient treatment of a paraneoplastic neurological syndrome (PNS) a second neoplasia was suspected in the patient. By the aid of whole body positron emission tomography with 18-fluorine fluoro-2-deoxy-glucose (FDG-PET) an adenocarcinoma of the cecum could be detected. Two months after surgery anti-Ma antibodies were negative. We conclude that a second neoplasia should be considered, if effective cancer treatment does not lead to improvement or stabilisation of a PNS. Tumor search should be exhaustive and include PET when conventional imaging fails to show a malignancy.

[Microdeletion 22q11.2. A too rarely diagnosed genetic change in psychiatric illnesses]. / Mikrodeletion 22q11.2. Eine zu selten diagnostizierte genetische Veränderung bei psychiatrischen Erkrankungen.

Microdeletion 22q11.2 with an estimated incidence of 1:4000 is known to cause the DiGeorge syndrome (DGS) or the velocardiofacial syndrome (VCFS), both usually being diagnosed in the newborn period or childhood. Recent studies have shown that children suffering from VCFS frequently develop psychiatric disorders in late adolescence or adulthood. Here we report the case of a 30-year-old man presenting with slight facial dysmorphisms, hypoparathyreoidism, minor cardiac anomalies, and slight cognitive impairments who had developed a severe personality disorder which eventually led to the diagnosis of microdeletion 22q11.2 with maternal inheritance. Psychiatric patients should be thoroughly examined for typical signs associated with this chromosomal anomaly. Genetic diagnosis is necessary because of the 50% probability of inheritance with possibly severe congenital anomalies. In view of a prevalence of 2% in an unselected group of patients with schizophrenic psychosis, microdeletion 22q11.2 is likely to be underdiagnosed.

Optimizing visual motion perception during eye movements.

We usually perceive a stationary, stable world and we are able to correctly estimate the direction of heading from optic flow despite coherent visual motion induced by eye movements. This astonishing example of perceptual invariance results from a comparison of visual information with internal reference signals predicting the visual consequences of an eye movement. Here we demonstrate that the reference signal predicting the consequences of smooth-pursuit eye movements is continuously calibrated on the basis of direction-selective interactions between the pursuit motor command and the rotational flow induced by the eye movement, thereby minimizing imperfections of the reference signal and guaranteeing an ecologically optimal interpretation of visual motion.

Cortical substrates of perceptual stability during eye movements.

We are usually unaware of retinal image motion resulting from our own movement. For instance, during slow-tracking eye movements, the world around us remains perceptually stable despite the retinal image slip induced by the eye movement. This example of perceptual invariance is achieved by subtracting an internal reference signal, reflecting the eye movement, from the retinal motion signal. If the two cancel each other, visual structures, which do not move, will also be perceived as nonmoving. If, however, the reference signal is too small or too large, a false eye-movement-induced motion of the external world will be perceived. We have exploited our ability to manipulate the size of the reference signal in an attempt to reveal the structures in visual cortex, encoding the perception of self-induced visual motion rather than the retinal motion signal. Using EEG and lately also MEG recordings in human subjects and single-unit recordings in monkeys, we have been able to show that our ability to perceive the world as stationary despite eye-movement-induced retinal image slip is based on "late" parts of the cortical hierarchy of motion processing, sparing the early stages up to cortical area MT and, among others, involving cortex at the junction between the parietal and temporal lobes close to the parieto-insular-vestibular cortex. Lesions of this network in humans render the visual system unable to compensate for the visual consequences of eye movements, giving rise to severe dizziness, whenever the eyes move smoothly.

Absence of a common functional denominator of visual disturbances in cerebellar disease.

Several studies have demonstrated disturbances of visual perception in patients suffering from cerebellar disease. In an attempt to determine the cause of these visual disturbances and thereby the cerebellar contribution to vision, we designed two sets of experiments in which we tested (i) the possibility of a general magnocellular deficit in cerebellar disease and (ii) the alternative possibility of impaired spatial attention underlying visual disturbances in cerebellar patients. The first set of experiments consisted of a test of position discrimination, a parvocellular function and tests tapping different aspects of motion perception including speed discrimination, direction discrimination and the ability to extract a coherent motion signal embedded in noise. The second set of experiments compared the performance on two different classes of texture discrimination. The first one required fast and precise shifts of focal spatial attention ('serial search'), the second one, testing preattentive texture discrimination ('pop-out'), did not. In the first set of experiments cerebellar patients were impaired on the position discrimination task as well as several, albeit not all, tests of motion perception. The pattern of disturbances obtained was neither compatible with the notion of a selective magnocellular deficit nor the idea, originally put forward by Ivry and Diener (J Cogn Neurosci 1991; 3: 355-66) that visual deficits are secondary to an impaired measurement of time. In the second set of experiments, cerebellar patients showed normal performance on pop-out tasks and normal performance on all variants of the serial search task except for the one requiring comparison of a single element presented with a sample of the target in short-term memory. In summary, our results support the existence of visual disturbances in cerebellar disease, but provide evidence against a common, simple denominator such as a timing deficit, deficient cerebellar modulation of magnocellular circuitry, deficits of spatial attention or visual working memory.

Impaired analysis of moving objects due to deficient smooth pursuit eye movements.

It is usually assumed that the raison d'être for smooth pursuit eye movements is an advantage in the visual analysis of moving objects due to the stabilization of the retinal image on the fovea. Although such benefits resulting from foveal pursuit are plausible, there have been few attempts to demonstrate them rigorously. Moreover, it is unknown whether and to what extent pursuit deficits due to neurological disease impair vision. In this study, therefore, we measured psychophysical thresholds for two different discrimination tasks assessing the visual analysis of moving objects as a function of smooth pursuit performance. Results from a group of healthy subjects were compared with those obtained from patients exhibiting catch-up saccades (n = 9) or saccadic intrusions in the form of square-wave jerks (n = 2). In a first set of experiments we measured acuity thresholds for Landolt optotypes moving horizontally at velocities of up to 14 degrees /s (dynamic visual acuity, DVA). In the control group (n = 20), DVA thresholds were indistinguishable from thresholds observed under stationary fixation due to efficient pursuit eye movements allowing continuous foveal stabilization of the retinal Landolt image. In contrast, all patients with catch-up saccades showed pursuit gains that decreased with increasing velocity, paralleled by a dramatic rise in DVA thresholds. Patients with square-wave jerks in turn revealed sufficient pursuit velocity but impaired foveation due to the involuntary saccades that occurred at similar frequencies independent of target velocity. In these patients, thresholds were more or less independent of the Landolt velocity but significantly raised compared with controls. Similar results were obtained in a test determining the sensitivity for vertical position steps of a given pursuit target. In summary, our results indicate that the lack of adequate pursuit eye movements is indeed deleterious for the visual analysis of moving objects.

An electrophysiological correlate of visual motion awareness in man.

It is usually held that perceptual spatial stability, despite smooth pursuit eye movements, is accomplished by comparing a signal reflecting retinal image slip with an internal reference signal, encoding the eye movement. The important consequence of this concept is that our subjective percept of visual motion reflects the outcome of this comparison rather than retinal image slip. In an attempt to localize the cortical networks underlying this comparison and therefore our subjective percept of visual motion, we exploited an imperfection inherent in it, which results in a movement illusion. If smooth pursuit is carried out across a stationary background, we perceive a tiny degree of illusionary background motion (Filehne illusion, or FI), rather than experiencing the ecologically optimal percept of stationarity. We have recently shown that this illusion can be modified substantially and predictably under laboratory conditions by visual motion unrelated to the eye movement. By making use of this finding, we were able to compare cortical potentials evoked by pursuit-induced retinal image slip under two conditions, which differed perceptually, while being identical physically. This approach allowed us to discern a pair of potentials, a parieto-occipital negativity (N300) followed by a frontal positivity (P300), whose amplitudes were solely determined by the subjective perception of visual motion irrespective of the physical attributes of the situation. This finding strongly suggests that subjective awareness of visual motion depends on neuronal activity in a parieto-occipito-frontal network, which excludes the early stages of visual processing.

[Sympathetic reflex dystrophy in circumscribed stenosis of the abdominal aorta. Case report and discussion of pathophysiologic principles]. / Sympathische Reflexdystrophie bei umschriebener Stenose der Aorta abdominalis. Kasuistik und Diskussion der pathophysiologischen Grundlagen.

Reflex sympathetic dystrophy (RSD) is a pain syndrome characterized by somatosensory and motor disturbances, as well as by autonomic and trophic changes. The term is used in a descriptive sense and does not imply specific mechanisms of pathogenesis. We report on a patient who fulfilled the clinical criteria of RSD and who also displayed increasing impairment of peripheral blood supply. Angiography revealed a circumscribed stenosis of the abdominal aorta adjacent to the bifurcation. Disturbances in peripheral circulation as a potential cause of RSD are discussed.

Gluteal compartment syndrome due to rhabdomyolysis after heroin abuse.

We report a 30-year-old man who developed painful swelling of his right leg and complete sciatic nerve palsy after an i.v. injection of heroin. Excessive elevation of serum creatine phosphokinase indicated the presence of rhabdomyolysis. Fasciotomy of the gluteus maximus led to rapid and complete recovery from sciatic nerve palsy. Nontraumatic rhabdomyolysis may cause a gluteal compartment syndrome that requires immediate fasciotomy.

False perception of motion in a patient who cannot compensate for eye movements.

We are usually unaware of the motion of an image across our retina that results from our own movement. For instance, during slow-tracking eye movements we do not mistake the shift of the image projected onto the retina for motion of the world around us, but instead perceive a stable world. Following early suggestions by von Helmholtz, it is commonly believed that this spatial stability is achieved by subtracting the retinal motion signal from an internal reference signal, such as a copy of the movement command (efference copy). Object motion is perceived only if the two differ. Although this concept is widely accepted, its anatomical underpinning remains unknown. Here we describe the case of a patient with bilateral extrastriate cortex lesions, suffering from false perception of motion due to an inability to take eye movements into account when faced with self-induced retinal image slip. This is indicated by the fact that during smooth-pursuit eye movements, he perceives motion of the stationary world at a velocity that corresponds to the velocity of his eye movement; that is, he perceives the raw retinal image slip uncorrected for his own eye movements. We suspect that this deficiency reflects damage of a distinct parieto-occipital region that disentangles self-induced and externally induced visual motion by comparing retinal signals with a reference signal encoding eye movements and possibly ego-motion in general.

[Cortical vertigo]. / Corticaler Schwindel.

Dizziness of cortical origin is the subjective correlate of a disturbance of spatial orientation resulting from cerebrocortical dysfunction. Cortical dizziness in the form of vertigo is rare. If present, it most probably reflects a dysfunction of a vestibular representation in the insula. It may be accompanied by tinnitus, sensory disturbance and possibly also spontaneous nystagmus. The dysfunction of this region may result either from a focal seizure or from a lesion, for instance due to ischemia. Nondirectional, visual dizziness is most probably much more common than vertigo. This latter type of dizziness results from a functional disturbance of those parts of parietooccipital cortex, contributing to the discrimination of self-induced and externally-induced retinal image slip. It is not accompanied by additional symptoms and should immediately cease upon closure of the eyes or avoidance of ego motion.

Modification of the Filehne illusion by conditioning visual stimuli.

During smooth pursuit eye movements made across a stationary background an illusory motion of the background is perceived (Filehne illusion). The present study was undertaken in order to test if the Filehne illusion can be influenced by information unrelated to the retinal image slip prevailing and to the eye movement being executed. The Filehne illusion was measured in eight subjects by determining the amount of external background motion required to compensate for the illusory background motion induced by 12 deg/sec rightward smooth pursuit. Using a two-alternative forced-choice method, test trials, which yielded the estimate of the Filehne illusion, were randomly interleaved with conditioning trials, in which high retinal image slip was created by background stimuli moving at a constant horizontal velocity. There was a highly reproducible monotic relationship between the size and direction of the Filehne illusion and the velocity of the background stimulus in the conditioning trials with the following extremes: large Filehne illusions with illusory motion to the right occurred for conditioning stimuli moving to the left, i.e. opposite to the direction of eye movement in the test trials, while conversely, conditioning stimuli moving to the right yielded Filehne illusions close to zero. Additional controls suggest that passive motion aftereffects are unlikely to account for the modulation of the Filehne illusion by the conditioning stimulus. We hypothesize that this modification might reflect the dynamic character of the networks elaborating spatial constancy.

Attenuation of a voltage-dependent sodium current by GABA (identified neurons, buccal ganglia, Helix pomatia).

The action of systemically applied GABA on voltage-dependent currents of the identified neurons B1-B4 in the buccal ganglia of Helix pomatia were investigated by conventional voltage clamp techniques. In the B4 neuron, superfusion with sodium-free solution or addition of tetrodotoxin to the bath medium abolished the voltage dependent inward current. This voltage dependent sodium current was reduced with GABA application. Muscimol exerted the same effect as GABA whereas administration of baclofen had no effect. Voltage-dependent sodium and calcium currents of the neurons B1-B3 remained unchanged with GABA application. It is concluded that GABA is capable of reducing voltage-dependent sodium currents of distinct neuronal individuals via a GABAA receptor-like structure.