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Biomedical subjects

T Brandt

Publications and source records attributed to T Brandt.

At least 127 records · Page 7Linked to original sources

Direction-specific impairment of motion perception and spatial orientation in downbeat and upbeat nystagmus in humans.

Downbeat and upbeat nystagmus can be classified as central vestibular syndromes in the vertical (pitch) plane of the vestibulo-ocular reflex (VOR) which are defined by ocular motor, perceptual, and postural manifestations. While the ocular motor syndrome was often studied investigations on the perceptual consequences for spatial orientation and motion perception are rare. Subjective visual straight ahead (SVA) and perception of object motion were measured in 11 patients with downbeat (n=6) and upbeat (n=5) nystagmus. Upward deviations of SVA (median +5.2 degrees) were found in downbeat nystagmus, and downward deviations (median -7.8 degrees) in upbeat nystagmus. SVA was deviated toward the slow phase of the vertical nystagmus in the pitch plane and associated with increased fore-aft body sway. Perception of object motion was more severely impaired for vertical (particularly for motion in the direction of slow nystagmus phases) than for horizontal directions in both downbeat and upbeat nystagmus. Impairment of motion perception in the vertical pitch plane of the VOR is beneficial to the extent that it alleviates disturbing oscillopsia due to the involuntary retinal slip. Thus, our findings confirm the hypothesis that downbeat and upbeat nystagmus reflect a central tone imbalance of the VOR in the vertical pitch plane with ocular motor, postural, and perceptual manifestations.

Adult↗

Stroke from internal carotid artery occlusion during mumps infection.

During the terminal incubation period of severe mumps infection, a 40-year-old patient suffered from large infarction in the right middle cerebral artery territory. The proximal right internal carotid artery (ICA) was occluded on angiography. Computed tomography of the neck detected a hemorrhage located ventromedial to the right common carotid artery. Four months later the right ICA was partly recanalized. Carotid surgery revealed an atherosclerotic plaque and a vessel wall, which was fragile and less compact than usually. A strong inflammatory reaction to mumps infection may have contributed to the pathogenesis of the cervical hemorrhage and to acute thrombosis and occlusion of the ICA.

Adult↗

Bilateral functional MRI activation of the basal ganglia and middle temporal/medial superior temporal motion-sensitive areas: optokinetic stimulation in homonymous hemianopia.

OBJECTIVE: To determine to what extent sensorimotor control is achieved for each hemisphere separately or interactively during small-field optokinetic stimulation in patients with complete homonymous hemianopia. DESIGN: Functional and structural neuroimaging using high-resolution magnetic resonance imaging. SETTING: University medical center research facility. PATIENTS: Three patients with complete homonymous hemianopia after acute infarction of the right posterior cerebral artery. MAIN OUTCOME MEASURES: Anatomical location of activated structures during horizontal optokinetic stimulation and T2-weighted anatomical magnetic resonance imaging. RESULTS: Occipitotemporal cortical areas (Brodmann areas 39 and 40) were the only activated cortical structures that showed statistically significant (P<.01) activation on the affected hemisphere. Of the subcortical areas, activation of thalamic nuclei appeared to be missing on the affected side, whereas the basal ganglia (putamen, globus pallidus, and caudate nucleus) were bilaterally activated. CONCLUSIONS: Bilateral activation of the basal ganglia confirms the concept of the basal ganglia-thalamocortical motor loop and of the efference copy of oculomotor pathways from each hemisphere. Our findings suggest 2 possible explanations for the activation of occipitotemporal areas (the human homolog of middle temporal/medial superior temporal areas) on the infarcted hemisphere: involvement of direct extrastriatal visual pathways or interhemispheric callosal connections between right and left middle temporal/medial superior temporal areas.

Aged↗

Diffusion-weighted MRI in transient global amnesia: elevated signal intensity in the left mesial temporal lobe in 7 of 10 patients.

Prompted by the findings of previous studies with positron emission tomography and single photon emission computed tomography, which demonstrated hypoperfusion or hyperperfusion in the left temporal lobe in isolated patients with transient global amnesia (TGA), we compared the sensitivity of diffusion-weighted (DW) magnetic resonance imaging (MRI) with that of conventional T1- and T2-weighted MRI in patients with TGA. Ten patients with the typical syndrome of a pure TGA were included in the study. For all patients, a coronal DW sequence, a steady-state free precession (SSFP) sequence, and conventional T1- and T2-weighted turbo spin-echo sequences were obtained. Seven of the 10 patients had elevated signal intensity in the left hippocampal region on DW MRI; moreover, 3 of these 7 patients exhibited bilateral signal abnormality in this sequence. All conventional T1- and T2-weighted images as well as all follow-up studies were normal. The signal elevation in DW MRI correlates with a decrease in the interstitial space and with cellular edema in the temporal lobe during TGA. The underlying pathomechanism causing this cellular edema cannot be clearly outlined using DW MRI. Our data are, however, compatible with spreading depression. This is the first study to show that DW MRI is a sensitive MRI method for evaluating TGA, especially in the early stage of the disease.

Aged↗

Cerebral functional magnetic resonance imaging of vestibular, auditory, and nociceptive areas during galvanic stimulation.

Cerebral activation was investigated with functional magnetic resonance imaging (fMRI) during galvanic stimulation of the mastoid in 6 normal volunteers. Cutaneous stimulation at the neck C4-5 level served as a control. During mastoid stimulation, bilateral vestibular activation occurred in the posterior insula (parietoinsular vestibular cortex, PIVC), the transverse temporal (Heschl's) gyrus, and thalamic pulvinar. The cutaneous pain elicited by galvanic stimulation caused bilateral activity of the medial part of the insula and the anterior median thalamus. Thus, galvanic stimulation at the mastoid level activates cortical areas of three different sensory systems in the insulathalamic region, the vestibular, the auditory, and the nociceptive systems.

Adult↗

Ultrastructural connective tissue abnormalities in patients with spontaneous cervicocerebral artery dissections.

The cause of spontaneous cervicocerebral artery dissection is unknown. An underlying arteriopathy due to a connective tissue disorder has often been presumed. We studied 25 patients with proven nontraumatic dissections. The ultrastructural morphology of dermal connective tissue components was assessed by transmission electron microscopy of skin biopsies. Ultrastructural abnormalities were seen in 17 (68%) patients, resembling in some cases the aberrations found in Ehlers-Danlos syndrome type II or III. These observations indicate a correlation of cervical artery dissections with connective tissue abnormalities. A structural abnormality in the extracellular matrix potentially caused by basic molecular defects is suggested and warrants further exploration.

Adult↗

Characterization of viral double-stranded RNA-binding proteins.

Several viruses have been shown to code for proteins that specifically bind to double-stranded RNA or RNA with large amounts of secondary structure. These proteins have been implicated in providing interferon resistance to viruses and in inhibiting induction of apoptosis by viruses, and have been suggested to be involved in regulation of viral and cellular protein synthesis in infected cells. This article describes methods for detecting and analyzing viral double-stranded RNA-binding proteins.

Blotting, Northern↗

Serum antibodies against membranous labyrinth in patients with "idiopathic" bilateral vestibulopathy.

To investigate the possibility of an autoimmune mechanism in idiopathic bilateral vestibulopathy (IBV), we screened patients' sera for antibodies against inner ear structures. IgG antibodies against membranous labyrinth (ampulla, semicircular canals, saccule and utricle) were detected in 8 of 12 patients by immunofluorescence on rat inner ear cryosections. All but one serum of 22 healthy controls and the sera of 6 patients with known autoimmune disorders showed only background staining. Low-titre anti-nuclear IgM antibodies were present in three control sera and one IBV serum. High-titre anti-nuclear IgM was found in a patient with lupus erythematosus and in one with scleroderma. Anti-nuclear IgM was not organ-specific. No human serum used contained detectable anti-vascular preformed antibodies. Cross-reactivity to sections of liver, kidney, cornea, brain and skeletal muscle was absent. Double-staining for IgG and F-actin, the primary constituent of hair cell cilia, did not show predominant Ig-coating of sensory hair cells. Immunosuppressive therapy in 3 IBV patients did not improve the disorder, probably owing to irreversible loss of sensory and neural structures. These data suggest that the bulk of anti-labyrinthine autoantibodies may be an epiphenomenon, yet a small subgroup of organ-specific autoantibodies may synergize with a cellular response in the development of vestibular lesions.

Autoantibodies↗

Incidence of post-lumbar puncture syndrome reduced by reinserting the stylet: a randomized prospective study of 600 patients.

The post-lumbar puncture syndrome (PLPS) can best be explained by prolonged spinal fluid leakage owing to delayed closure of a dural defect. Its incidence after spinal anaesthesia is much lower than after diagnostic lumbar puncture (LP). This difference could be caused by a strand of arachnoid, which might enter the needle with the outflowing cerebrospinal fluid (CSF) during diagnostic LP and upon removal of the needle be threaded back through the dura to produce prolonged CSF leakage. To find a technique that further reduces the incidence of PLPS, this hypothesis was tested by evaluating the effect that reinserting the stylet before removing the needle had on the incidence of PLPS. By reinserting the stylet to the tip of the needle, the hypothesized strand would be pushed out, thereby reducing the frequency of PLPS. Sprotte's "atraumatic needle" (21 gauge) was used for LP. A total of 600 patients participated in the prospective study. They were randomized into two groups and questioned about their complaints every day for up to 7 days after the LP. All LPs were performed by two experienced neurologists (T.B., M.S.). In 300 patients, the stylet was reinserted to the tip of the eedle; in the other 300 it was not reinserted. Whereas 49 of the 300 patients without reinsertion developed PLPS, only 15 of the 300 patients with reinsertion did. This significant difference (16.3 vs 5.0%, P < 0.005, chi square test) supports our hypothesis. On the basis of our results, we recommend reinserting the stylet before removing the needle in order to reduce the incidence of PLPS.

Adult↗

Effects of galvanic vestibular stimulation on otolithic and semicircular canal eye movements and perceived vertical.

OBJECTIVE: The aim of this study was to determine the otolithic and semicircular canal effects of galvanic vestibular stimulation with increasing current strengths on eye movements and the perception of verticality. METHODS: We measured (1) 3-dimensional eye movements, (2) subjective tilt of the peripheral visual field, and (3) subjective tilt of a central vertical line in 12 healthy subjects during galvanic vestibular stimulation. A rectangular, unipolar binaural electric current was applied to each subject's mastoid. RESULTS: Anodal stimulation of the right mastoid led to an ipsiversive tonic ocular torsion of up to 5.4 degrees, to a contralateral tilt of both the peripheral visual field (1-9 degrees), and a central vertical line (0.5-6.2 degrees) increasing in amplitude with increasing current strengths applied. This reflects otolith stimulation. In most subjects, current strengths of 3 mA or more elicited a slight (horizontal-) torsional nystagmus (amplitude 1-2 degrees) that was superimposed on static torsion. This reflects horizontal and vertical semicircular canal stimulation. A correlation was found in the amount of the 3 measured parameters and the strength of the applied current. CONCLUSIONS: Thus, galvanic vestibular stimulation at low current intensities (1-3 mA) preferably excites otolith responses, which increase with increasing current intensity. With higher current intensity above 3 mA, additional semicircular canal responses are elicited in the form of horizontal-rotatory nystagmus superimposed on static torsional deviations. The lack of a vertical deviation and nystagmus can be explained by the counterdirected vertical components of the anterior and posterior semicircular canal.

Adult↗

Perceptual and oculomotor effects of neck muscle vibration in vestibular neuritis. Ipsilateral somatosensory substitution of vestibular function.

Afferent cervical somatosensory input may substitute for absent vestibular information as part of central vestibular compensation after unilateral peripheral vestibular deficit. In order to determine the particular contribution of neck muscle spindles to the perception of body orientation and to the oculomotor system, we measured (i) the subjective visual straight ahead (SVA) by psychophysical tests and (ii) the changes in eye position by video-nystagmography during unilateral stimulation of the posterior neck muscles by vibration (100 Hz). Twenty-five patients with subacute unilateral vestibular lesion (vestibular neuritis) and 25 controls participated in the study. Vibration elicited a horizontal displacement of SVA towards the side of stimulation in all subjects. Mean displacement (+/- SD) was 3.28 +/- 2.96 degrees for right-side and 3.45 +/- 2.93 degrees for left-side stimulation in controls. Muscle stimulation on the patients' lesion side induced a significantly higher displacement (11.51 +/- 6.63 degrees) than contralateral stimulation (3.04 +/- 2.95 degrees, P < 0.01, paired Student's t test). The mean difference during stimulation between the two sides in the patients was 8.02 +/- 5.52 degrees; in the controls, however, it was only 0.74 +/- 0.47 degree (P < 0.001, Student's t test). This asymmetry increased gradually in patients over a period of weeks, reaching a maximum at days 60-80 and declining thereafter. Videonystagmography revealed that ipsilateral stimulation in patients induced large horizontal eye deviations of up to 25 degrees towards the side of the lesion (9.1 +/- 7.6 degrees, n = 18). Contralateral stimulation induced only small shifts, which were within the range of controls. The correlation coefficient between displacement of the SVA and change in eye position was high (r = 0.94, P < 0.0001), indicating that the shift of SVA is the perceptual correlate of the directional change of gaze in space. This interpretation was supported by two control experiments in which the subject was required to (i) indicate the subjective straight ahead by finger-pointing with the eyes closed and (ii) adjust SVA when looking through horizontally reversing prisms. Vibration of neck muscles caused almost no displacement of the SVA when it was indicated by pointing with the eyes closed, but reversed the direction of the displacement if the subject wore reversing prisms. In summary, our data showed: (i) an increase in muscle spindle input following unilateral vestibular lesion; (ii) this increase is asymmetrical, restricted to the affected side, and gradually builds up over weeks; and (iii) the perceived effects during vibration are secondary to changes in eye position rather than changes in cortical representation of body orientation. This is the first study to demonstrate a unilateral increase in somatosensory weight, which substitutes for missing vestibular input.

Adolescent↗

Horizontal or vertical optokinetic stimulation activates visual motion-sensitive, ocular motor and vestibular cortex areas with right hemispheric dominance. An fMRI study.

The differential effects of optokinetic stimulation with and without fixation suppression were analysed in an fMRI study in 10 right-handed healthy subjects. Horizontal and vertical small-field optokinetic stimulation activated the same multiple visual, ocular motor and vestibular cortical and subcortical areas in both hemispheres. The extent of activation in each hemisphere was independent of the stimulus direction. All activated areas representing cortical (occipitotemporal cortex, posterior parietal cortex, precentral and posterior median frontal gyrus, prefrontal cortex, medial part of the superior frontal gyrus) and subcortical (caudate nucleus, putamen, globus pallidus and paramedian thalamus) ocular motor structures were activated during optokinetic stimulation as well as during fixation suppression of optokinetic nystagmus. However, the activation was significantly stronger with optokinetc nystagmus compared with fixation suppression. The only relatively increased activity during fixation suppression was seen in the medial part of the superior frontal gyrus (supplementary eye field) and the anterior cingulate gyrus. The anterior insula and the posterior insula (human homologue of the parieto-insular vestibular cortex) were activated during optokinetic nystagmus but not during fixation suppression. A significant right hemispheric predominance (regardless of stimulus direction) was found under both conditions in the visual motion-sensitive and ocular motor areas of the cortex, except the supplementary eye field and anterior cingulate gyrus. This was most prominent in the occipitotemporal cortex, but did not occur in the primary visual cortex and in subcortical ocular motor structures (putamen, globus pallidus and caudate nucleus). Thus, cortical and subcortical activation patterns did not differ for horizontal and vertical optokinetic stimulation, and there was distinct right-hemisphere dominance for visual motion-sensitive and cortical ocular motor areas and the thalamus. Fixation suppression of optokinetic nystagmus yielded four different results: (i) increased activation in the supplementary eye field and anterior cingulate gyrus; (ii) unchanged activation in the visual cortex; (iii) decreased activation in most of the ocular motor areas; and (iv) suppressed activation in the anterior and posterior insula and the thalamus. Activation of the parieto-insular vestibular cortex may be related to ocular motor function rather than self-motion perception.

Adult↗

Reciprocal inhibitory visual-vestibular interaction. Visual motion stimulation deactivates the parieto-insular vestibular cortex.

The vestibular system--a sensor of head accelerations--cannot detect self-motion at constant velocity and thus requires supplementary visual information. The perception of self-motion during constant velocity movement is completely dependent on visually induced vection. This can be linear vection or circular vection (CV). CV is induced by large-field visual motion stimulation during which the stationary subject perceives the moving surroundings as being stable and himself as being moved. To determine the unknown cortical visual-vestibular interaction during CV, we conducted a PET activation study on CV in 10 human volunteers. The PET images of cortical areas activated during visual motion stimulation without CV were compared with those with CV. Hitherto, CV was explained neurophysiologically by visual-vestibular convergence with activation of the vestibular nuclei, thalamic subnuclei and vestibular cortex. If CV were mediated by the vestibular cortex, one would expect that an adequate visual motion stimulus would activate both the visual and vestibular cortex. Contrary to this expectation, it was shown for the first time that visual motion stimulation with CV not only activates a medial parieto-occipital visual area bilaterally, separate from middle temporal/medial superior temporal areas, it also simultaneously deactivates the parieto-insular vestibular cortex. There was a positive correlation between the perceived intensity of CV and relative changes in regional CBF in parietal and occipital areas. These findings support a new functional interpretation: reciprocal inhibitory visual-vestibular interaction as a multisensory mechanism for self-motion perception. Inhibitory visual-vestibular interaction might protect visual perception of self-motion from potential vestibular mismatches caused by involuntary head accelerations during locomotion, and this would allow the dominant sensorial weight during self-motion perception to shift from one sensory modality to the other.

Adult↗

Safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody): an open-label, dose escalation study in patients hospitalized for acute stroke.

BACKGROUND AND PURPOSE: To obtain information on the safety, pharmacokinetics and biological activity of enlimomab (anti-ICAM-1 antibody) in stroke patients. METHODS: An open, uncontrolled, dose titration study was conducted in 32 patients hospitalized for stroke. Patients received one of four fixed dose regimens of enlimomab. A loading dose of enlimomab administered within 24 h of the onset of stroke symptoms was followed by four daily maintenance doses; total doses ranged from 140 to 480 mg. RESULTS: The pharmacokinetic target levels (enlimomab serum levels of >/=10 microg/ml) were consistently achieved in all patients receiving dose regimens III and IV. Non-serious adverse events thought to be causally related to enlimomab administration included headache, vomiting and extrasystoles. Serious events occurred in 14 patients, including pneumonia, sepsis, cardiac failure and cardiac arrest. The only serious adverse event considered to be related to enlimomab administration was an anaphylactoid reaction, in a patient who received an unfiltered loading dose of antibody; the patient recovered. The overall mortality in the study was 15.6% and the 30-day mortality was 12.5%. There was no increase in the frequency of adverse events with increasing doses of enlimomab. CONCLUSIONS: Doses of enlimomab between 140 and 480 mg administered over 5 days did not increase the risk of adverse events in patients with ischaemic or haemorrhagic stroke during an observation period of 30 +/- 10 days. A loading dose of 160 mg followed by four daily maintenance doses of 40 mg appears to be suitable for further study.

Acute Disease↗

Role of CT angiography in patient selection for thrombolytic therapy in acute hemispheric stroke.

BACKGROUND AND PURPOSE: It has been shown that thrombolytic therapy can improve clinical outcome in a subgroup of patients with acute cerebral ischemia. This subgroup was characterized by certain clinical and imaging findings (eg, moderate to severe neurological deficit for less than 3 to 6 hours, occlusion of the middle cerebral artery, lack of extended infarct signs on CT, and efficient leptomeningeal collaterals). Although not part of published prospective randomized rtPA trials, information about the status of the brain vessels would be helpful in the selection of patients who may benefit the most. Our purpose was to determine the feasibility of CT angiography (CTA) in patients with acute hemispheric ischemia and to evaluate its relevance for thrombolytic therapy. METHODS: CTA was performed in 40 consecutive patients (11 women and 29 men; age range, 19 to 80 years) with moderate or severe symptoms (National Institutes of Health Stroke Scale score of > or =8) of acute hemispheric ischemia. CTA findings were compared with Doppler ultrasonography (US; n=22) and intra-arterial digital subtraction angiography (DSA; n=7). Twenty patients received thrombolytic therapy, the remaining patients received intravenous heparin. RESULTS: Images and 3-dimensional reconstructions of diagnostic quality could be obtained in all patients. Thirty-four patients had a vessel occlusion. The extent of leptomeningeal collaterals correlated significantly with the outcome after thrombolytic therapy (rs=0.46, P<0.05). The evaluation of diagnostic accuracy showed a high agreement with US (22 of 22) and DSA (6 of 7). CONCLUSIONS: CTA can provide important information for the initiation of therapy in patients with acute hemispheric ischemia. Identification of patients with autolyzed thrombi, occlusion of the internal carotid artery bifurcation, and poor leptomeningeal collaterals is feasible with the use of CTA. These patients may have little potential for benefit from thrombolytic therapy.

Acute Disease↗

Vestibular exercises improve central vestibulospinal compensation after vestibular neuritis.

OBJECTIVE AND BACKGROUND: Animal experiments have shown that central vestibular compensation of unilateral peripheral vestibular lesions can be improved by vestibular exercises. There are, however, no equivalent clinical studies on the efficacy of such specific physiotherapy on acute unilateral peripheral vestibular lesions in humans. DESIGN AND METHODS: To quantify the differential effects of specific vestibular exercises on central compensation in patients with an acute/subacute unilateral vestibular lesion (vestibular neuritis), we determined the time course of recovery of 1) the ocular torsion (OT) for the vestibulo-ocular system, 2) the subjective visual vertical (SVV) for perception, and 3) the total sway path (SP) values for postural control in 19 patients with and 20 patients without vestibular exercises. All patients had a persisting peripheral vestibular deficit for at least 30 days (statistical end point). RESULTS: Although normalization of OT and SVV was similar in the control and physiotherapy groups, the total SP values on day 30 after symptom onset differed significantly: 3.2 +/- 1.9 m/min in the physiotherapy group and 16.9 +/- 6.1 m/min in the control group (ANOVA, p < 0.001). CONCLUSIONS: This prospective clinical study suggests that specific vestibular exercises improve vestibulospinal compensation in patients with acute peripheral vestibular lesions.

Adult↗