Biomedical subjects

A Schnitzler

Publications and source records attributed to A Schnitzler.

At least 19 recordsLinked to original sources

PubMed2026

Multiregion profiling of genomic and transcriptional heterogeneity in head and neck squamous-cell carcinoma.

BACKGROUND: Intratumoral heterogeneity (ITH) is thought to contribute to tumour evolution and treatment resistance but its biological and clinical significance in localised head and neck squamous-cell carcinoma (HNSCC) remains incompletely understood. PATIENTS AND METHODS: In the prospective SCANDARE study, we analysed 87 patients with resectable HNSCC treated with upfront surgery. Two to five spatially distinct tumour regions per patient underwent pathological evaluation, targeted DNA sequencing, and bulk RNA sequencing. Genomic ITH (gITH) was quantified using clonal deconvolution and Shannon diversity indices, whereas transcriptional heterogeneity (tITH) was assessed using the intratumour expression distance metric. Associations between ITH, molecular features, tumour microenvironment composition, and clinical outcomes were explored using multivariable statistical models. RESULTS: Pathology-based spatial heterogeneity showed limited prognostic value. gITH was common, with 37% of tumours displaying regionally heterogeneous pathogenic variants, including spatially actionable alterations in 10% of patients. In an initial multivariable Cox model, higher gITH was associated with shorter disease-free survival. However, after Ridge-penalised modelling and bootstrap internal validation, the effect size was attenuated [corrected hazard ratio 1.42, 95% confidence interval (CI) 0.91-2.75]. The overall model retained moderate discriminative performance (optimism-corrected C-index 0.69, 95% CI 0.59-0.79). gITH was associated with tumour cellularity, reduced estimated endothelial cell infiltration, and alterations in KMT2C and PIK3CA. tITH differed according to human papillomavirus (HPV) status, with lower tITH in HPV-positive tumours, and was associated with distinct biological pathways and genomic alterations. Genomic and tITH were not correlated. CONCLUSIONS: This prospective multiregion study provides a comprehensive characterisation of genomic and tITH in localised HNSCC. Our findings highlight substantial spatial molecular diversity within primary tumours and suggest potential associations between heterogeneity, tumour biology, and clinical outcome that warrant validation in independent cohorts.

head and neck squamous-cell carcinoma (HNSCC)↗

PubMed2006

Observation of a finger or an object movement primes imitative responses differentially.

Behavioural advantages for imitation of human movements over movements instructed by other visual stimuli are attributed to an 'action observation-execution matching' (AOEM) mechanism. Here, we demonstrate that priming/exogenous cueing with a videotaped finger movement stimulus (S1) produces specific congruency effects in reaction times (RTs) of imitative responses to a target movement (S2) at defined stimulus onset asynchronies (SOAs). When contrasted with a moving object at an SOA of 533 ms, only a human movement is capable of inducing an effect reminiscent of 'inhibition of return' (IOR), i.e. a significant advantage for imitation of a subsequent incongruent as compared to a congruent movement. When responses are primed by a finger movement at SOAs of 533 and 1,200 ms, inhibition of congruent or facilitation of incongruent responses, respectively, is stronger as compared to priming by a moving object. This pattern does not depend on whether S2 presents a finger movement or a moving object, thus effects cannot be attributed to visual similarity between S1 and S2. We propose that, whereas both priming by a finger movement and a moving object induces processes of spatial orienting, solely observation of a human movement activates AOEM. Thus, S1 immediately elicits an imitative response tendency. As an overt imitation of S1 is inadequate in the present setting, the response is inhibited which, in turn, modulates congruency effects.

Adult↗

PubMed2006

[Radiculopathy following intrathecal baclofen pump implantation].

INTRODUCTION: Intrathecally delivered baclofen has been used as a treatment for severe spasticity since 1984. After a successful intrathecal baclofen trial, a programmable drug delivery system was implanted. Few early complications such as infection or hematoma are observed after this surgery. OBJECTIVE: To describe an unusual and unknown complication of intrathecal baclofen therapy. METHOD: We report 2 cases of complications of intrathecal baclofen therapy, radiculalgy, that appeared early after pump implantation. The clinical symptoms and computed tomography (CT) results are described. RESULTS: The first patient described pain, which evoked left S1 radiculopathic features. The second had left L5 radiculopathic involvement. The mean pain level was estimated on a 10-point visual analog scale as 7.5 (range 4-9). Lumbar CT scan showed a conflict between the symptomatic root and the catheter and eliminated other causes of the symptoms. Treatment with analgesic drugs was successful in 1 patient. The other presented with proximal disconnection of the catheter, which led to surgical replacement of the catheter. The pain disappeared after this surgery. CONCLUSION: Intrathecal baclofen therapy with a subcutaneously implanted progammable pump can be complicated by radiculalgy secondary to a conflict between the catheter and symptomatic root. The diagnosis is made by CT lumbar scan. If medical treatment is not sufficient, surgery could be proposed to replace the catheter.

Adult↗

PubMed2006

[Psychobehavioural assessment for chronic low back pain].

INTRODUCTION: Psychobehavioural assessment may be a complementary approach to assess response to treatment for pain and disability in patients with low back pain. OBJECTIVES: To assess the correlation between psychobehavioural factors and pain and disability in patients with chronic low back pain in France. METHODS: We asked 83 patients with chronic low back pain to complete questionnaires during a primary care consultation by a general practitioner. Pain was measured by a visual analog scale (VAS), disability by the Quebec Back Pain Disability Scale and psychobehavioural factors by the Fear-Avoidance Beliefs Questionnaire (FABQ) and the Coping Strategy Questionnaire (CSQ). RESULTS: Pain was poorly correlated with anxiety (R = 0.36) and scores on the FABQ 1 (R = 0.46) and FABQ 2 (R = 0.30) and not correlated with depression (R = 0.22), duration of pain evolution (R = 0,10) and body mass index (R = 0.12). The duration of stopping work was poorly correlated with disability (R = 0.35) and FABQ 1 score (R = 0.43) and not correlated with pain (R = 0.11), anxiety (R = 0.11), depression (R = 0.26) and FABQ 2 score (R = 0.23). Disability was poorly correlated with scores on the FABQ 1 (R = 0.45) and FABQ 2 (R = 0.3), anxiety (R = 0.39) and depression (R = 0.47) and not correlated with pain (R = 0.25). Dramatization is the only way to cope with pain and was correlated with pain (R = 0.34), scores on the FABQ 1 (R = 0.47) and FABQ 2 (R = 0.43), disability (R = 0.38), anxiety (R = 0.44) and depression (R = 0.46). The use of prayer was poorly correlated with FABQ 1 score (R = 0.37) and anxiety (R = 0.30). Distraction was poorly correlated with scores on the FABQ 1 (R = 0.40) and FABQ 2 (R = 0.30). No strategy was correlated with duration of pain and stopping work. DISCUSSION-CONCLUSION: All the correlation assessments with psychobehaviour factors are weak. So evaluating each of these parameters will be interesting. Duration of pain was not correlated with increasing pain or change in behavioural strategy. Psychobehavioural factors are more invalidating than pain. More study is needed to assess psychobehavioural therapies in patients with low back pain.

Adult↗

PubMed2006

[Disabled workers with motor impairments: data from an occupational health service].

INTRODUCTION: Mediclen is an occupational health service in charge of following-up 36,736 workers (divided among 1770 companies) in 3 cities of an area near Paris. The employment rate of disabled people among the French population is not well known (rough estimate 4.4%), and few studies have reported on the situation of workers with a motor impairment. SUBJECTS AND METHOD: The recent computerization of medical records allowed us to identify 195 workers considered disabled by the French administration (i.e. 0.55% of the 36,736 workers followed up in 2002). Among these, 26 had a motor impairment. RESULTS: Twenty-one neurological disabilities were central and 5 were peripheral or neuromuscular. The workers were 44-years-old. Only two workers had a severe handicap. Companies had to adapt workstations for half of the workers, with the advice of neurologists (7 of 10 advice given) and once a physical medicine doctor. DISCUSSION-CONCLUSION: The integration of people with motor impairments into the world of work is rare and difficult. This practical experience showed the difficulties people with motor impairment face. Close collaboration of physical medicine services with occupational health services is necessary to improve the integration of this population into the world of work.

Adult↗

PubMed2005

Task-dependent oscillations during unimanual and bimanual movements in the human primary motor cortex and SMA studied with magnetoencephalography.

The neural mechanisms subserving uni- and bimanual control of movements are not well understood. Nevertheless, recent studies indicate a functional role of oscillatory activity in movement control and point towards a hemispheric asymmetry in motor control. This study specifically addresses the issues of (i) task-relatedness, (ii) hemispheric symmetry, and (iii) frequency specificity of the measures power, cerebro-muscular coherence, and cerebro-cerebral coherence in bilateral primary motor cortex and supplementary motor area (SMA). We have studied 10 right-handed subjects with simultaneous recordings of magnetoencephalography and surface electromyography during different unimanual and bimanual tasks. Using the analysis technique Dynamic Imaging of Coherent Sources (DICS), left and right primary motor cortex and SMA were functionally localized. Power, cerebro-musclar coherence, and cerebro-cerebral coherence between these areas were computed for four frequency bands in each condition and subjected to ANOVA. Results show a task-specific modulation of power and coherence, and further indicate a hemispheric asymmetry in the control of unimanual and bimanual movements. In addition, different frequency bands showed different task-dependent variations. The gamma band (26-40 Hz) showed strongest modulation for cerebro-muscular coherence and was strongest for the isometric contraction conditions. In contrast, the beta band (13-24 Hz) showed the strongest variations between static and dynamic conditions, and seems to play a particular role in movement control. In summary, our results indicate a differential functional role of oscillatory activity and coupling in the motor system.

Adult↗

PubMed2005

[Constituted adult equine from the ankle: surgical treatment by Ilizarov external fixator].

INTRODUCTION: Ilizarov's external fixator indications are classically used in children to lengthen the lower limbs. This technique is used for adults to gradually correct articular limitations, especially in the knee, ankle and foot. METHOD AND RESULTS: We report a case of a 53-year-old patient with distal microangiopathy of the lower limbs leading to amputation of the toes and a bilateral, direct, irreducible, isolated equine feature? from the back foot to 0/50/60 degrees? on retraction of the Achilles tendon. The aim of patient management was to regain walking ability. Because of vascular and cutaneous fragility, the classical surgical treatment was contra-indicated. Progressive reduction by Ilizarov's external fixator was tried. Dorsal inflection was obtained by twice-daily screwing until a radiological angle of 90 degrees was obtained between the tibia and talus. At ten weeks post-surgery, the dorsal voluntary inflection ankle amplitude was symmetrical to 0/10/60 degrees. The patient walked with orthopaedic shoes compensating for the few degrees of residual equine. DISCUSSION: Correction of adult equine without osseous deformation by Ilizarov's external fixator should be considered when conventional surgery is contra-indicated.

Age Factors↗

PubMed2004

Pathological oscillatory coupling within the human motor system in different tremor syndromes as revealed by magnetoencephalography.

Whole-head MEG-systems and modern spatial-filter-based analysis tools recently provided new possibilities to analyze non-invasively cerebral networks of human tremor syndromes. We compared tremor syndromes in Parkinsonian patients with a typical resting tremor as well as in patients with hepatic encephalopathy (HE) with a postural tremor called "mini-asterixis". In 6 patients with idiopathic Parkinson's disease (PD) we found strong coherence between the electromyography (EMG) of forearm muscles and activity in the contralateral primary motor cortex (M1) at tremor frequency but also at double tremor frequency. Furthermore, significant coherences were observed between M1 and medial wall areas (CMA/SMA), lateral premotor cortex, diencephalon, SII cortex, posterior parietal cortex and the contralateral cerebellum at tremor and, stronger, at double tremor frequency. In contrast, in 6 patients with "mini-asterixis" and HE due to chronic liver cirrhosis excessive corticomuscular coherence occurred at the individual tremor frequency between EMG and M1 activity. Interestingly, thalamus-M1 coupling was significantly altered towards lower frequencies matching the individual frequency of the mini-asterixis. Cerebro-muscular or cerebro-cerebral coupling at double tremor frequency was not observed. Therefore, "mini-asterixis" reflects most likely a pathologically decelerated and augmented synchronized rhythmical motor cortical output. This could be due to functional alterations in the M1-basal-ganglia-thalamo-cortical loops in severe HE. In summary, tremor syndromes in PD as well as in patients with HE and "mini-asterixis" are characterized by pathological oscillatory activity within cerebral networks of motor areas. However, the present study shows different mechanisms of tremor generation in PD and HE patients.

Evoked Potentials, Motor↗

PubMed2004

Use-dependent cortical plasticity in thalidomide-induced upper extremity dysplasia: evidence from somaesthesia and neuroimaging.

In this study cerebral reorganization was investigated in thalidomide-damaged subjects who use their feet to compensate for their malformed upper extremities. Tactile localization across toes was combined with fMRI to study use-dependent plasticity of the human somatosensory cortex. The manner of compensatory foot use was assessed by a questionnaire. In the behavioural experiment toes were stimulated with above threshold monofilaments and subjects had to report which toe was stimulated. When feet were employed for all everyday actions subjects made significantly fewer errors in the localization task. In subjects who use their feet only for specific actions such as grasping objects there were as many localization errors as in the control group of thalidomide-affected subjects with normal extremities. However, the patterns of mislocalizations were different with less errors occurring for the toe of the dominant foot involved in these actions. Functional MRI showed stronger haemodynamic responses to electrical stimulation of the toes in subjects using their feet for everyday actions as compared to controls. Our data show that long-term use of the feet for fine sensorimotor skills leads to better performance in tactile localization and changes in cerebral SI representation supporting the notion of use-dependent plasticity in the somatosensory cortex.

Activities of Daily Living↗

PubMed2004

[Cortical representation of pain].

Contrary to the traditional view that the cerebral cortex is not involved in pain perception an extensive cortical network associated with pain processing has been revealed during the past decades. This network consistently includes the primary (S1) and secondary somatosensory cortices (S2), the insular cortex, and the anterior cingulate cortex (ACC). These cortical areas are organized in parallel and contribute to different dimensions of pain experience. The S1 cortex is mainly involved in discriminative aspects of pain, while the S2 cortex seems to have an important role in cognitive aspects of pain perception. The insula has been proposed to be involved in autonomic reactions to noxious stimuli and in pain-related learning and memory. The ACC is closely related to pain affect and may subserve the integration of general affect, cognition, and response selection. Furthermore, first pain appears to be particularly related to activation of S1 whereas second pain is closely related to ACC activation.

Animals↗

PubMed2003

Mini-asterixis in hepatic encephalopathy induced by pathologic thalamo-motor-cortical coupling.

Recently, it was shown that a slowed motor cortical drive in hepatic encephalopathy (HE) results in mini-asterixis (MA). During forearm elevation, the authors have now investigated the coupling between motor cortex and thalamic activity using magnetoencephalography in six cirrhotic patients with HE and MA and in six control subjects. HE patients showed thalamo-motor-cortical coupling at a significantly lower frequency than the coupling in control subjects. The pathologic motor cortical drive in HE probably results from altered thalamocortical oscillatory coupling.

Aged↗

PubMed2003

Properties of MEG tomographic maps obtained with spatial filtering.

Magnetoencephalography (MEG) has, in comparison with other functional imaging modalities, unique properties which makes it the prime candidate for the noninvasive investigation of long-range oscillatory interactions in the human brain. Recent methodological developments based on spatial filtering introduced the computation of functional tomographic maps covering the entire brain and representing the distribution of coherence to a given reference signal or the distribution of power. Because of the spatially inhomogeneous sensitivity profile of the MEG sensors, the spatial resolution of the resulting functional maps is not isotropic across the brain. Here, we introduce a convenient analytic expression for the computation of the spatial resolution at any given point in the brain. We derive the dependence of the resolution on the signal-to-noise ratio and on the changes of the leadfields. The resolution map can be displayed on anatomical MRI in the same way as the functional maps. In addition, we establish a procedure for computing a confidence volume of local maxima which is based on a bootstrap method. The confidence volume is a measure for the uncertainty of the localization. It is important for assigning local maxima of activation to specific anatomical structures and may be used to test for differences in localization between different experimental conditions.

Artifacts↗

PubMed2002

The neural basis of intermittent motor control in humans.

The basic question of whether the human brain controls continuous movements intermittently is still under debate. Here we show that 6- to 9-Hz pulsatile velocity changes of slow finger movements are directly correlated to oscillatory activity in the motor cortex, which is sustained by cerebellar drive through thalamus and premotor cortex. Our findings suggest that coupling of 6- to 9-Hz oscillatory activity in the cerebello-thalamo-cortical loop represents the neural mechanism for the intermittent control of continuous movements.

Adult↗

PubMed2002

Cortical origin of mini-asterixis in hepatic encephalopathy.

The authors investigated 12 patients with cirrhosis who had hepatic encephalopathy (HE): six with continuous mini-asterixis and six with subclinical HE without asterixis. They studied the coupling between hand-muscle electromyography (EMG) recordings and brain activity recorded by magnetoencephalography. On forearm elevation, patients with tremor developed excessive coupling between activity in the motor cortex (M1) and contralateral hand-muscle EMG recordings at the frequency of mini-asterixis, which was not found in controls. The corticomuscular coupling demonstrates the involvement of M1 in asterixis and may reflect a pathologically slowed and synchronized motor cortical drive.

Adult↗

PubMed2001

Dynamic imaging of coherent sources: Studying neural interactions in the human brain.

Functional connectivity between cortical areas may appear as correlated time behavior of neural activity. It has been suggested that merging of separate features into a single percept ("binding") is associated with coherent gamma band activity across the cortical areas involved. Therefore, it would be of utmost interest to image cortico-cortical coherence in the working human brain. The frequency specificity and transient nature of these interactions requires time-sensitive tools such as magneto- or electroencephalography (MEG/EEG). Coherence between signals of sensors covering different scalp areas is commonly taken as a measure of functional coupling. However, this approach provides vague information on the actual cortical areas involved, owing to the complex relation between the active brain areas and the sensor recordings. We propose a solution to the crucial issue of proceeding beyond the MEG sensor level to estimate coherences between cortical areas. Dynamic imaging of coherent sources (DICS) uses a spatial filter to localize coherent brain regions and provides the time courses of their activity. Reference points for the computation of neural coupling may be based on brain areas of maximum power or other physiologically meaningful information, or they may be estimated starting from sensor coherences. The performance of DICS is evaluated with simulated data and illustrated with recordings of spontaneous activity in a healthy subject and a parkinsonian patient. Methods for estimating functional connectivities between brain areas will facilitate characterization of cortical networks involved in sensory, motor, or cognitive tasks and will allow investigation of pathological connectivities in neurological disorders.

Algorithms↗

PubMed2001

Involvement of the motor cortex in pseudochoreoathetosis.

The pathophysiological background of involuntary movements in pseudochoreoathetosis is unclear. We therefore recorded in four patients with pseudochoreoathetosis and in six age-matched controls cortical activity with a whole-head magnetoencephalography (MEG) system and surface EMGs from hand muscles. Subjects performed the following tasks: 1) rest, and 2) constant finger stretch during forearm elevation; controls additionally simulated pseudochoreoathetotic finger movements. During rest, the patients showed involuntary finger movements associated with excessive MEG-EMG coherence at frequencies between 6 and 20 Hz, whereas coherence in controls simulating pseudochoreoathetotic movements did not exceed noise level (P < 0.02). During finger stretch, MEG-EMG coherence in patients was similar to that of controls. Cortical sources of MEG-EMG coherence in patients were localized in the contralateral motor cortex. We conclude that pseudochoreoathetosis is associated with pathologically increased corticomuscular coherence and thus differs, neurophysiologically, from voluntarily simulated pseudochoreoathetotic movements. The enhanced MEG-EMG coherence in pseudochoreoathetosis probably reflects a pathologically strong motor cortical drive of spinal motorneurons after deafferentation.

Adult↗

PubMed2001

Motor impairment in patients with parietal lesions: disturbances of meaningless arm movement sequences.

The execution of meaningless movement sequences was studied in 12 patients with lesions of the parietal cortex in comparison to the performance of age- and sex-matched controls. Five sequences of increasing complexity had to be performed by imitation and after verbal instruction. The performance errors were qualitatively scored by means of four error categories (temporal or spatial error, addition or omission of movement components). This study examined whether the error scores depended on instruction modality, movement complexity or lesion side. Patients with left parietal lesions produced more errors than those with right parietal lesions and control subjects. While additions or omissions of movement components occurred almost equally in all groups, temporal and spatial errors were more frequent in patients with left parietal lesions only. In addition, only the latter group showed a significant increase of error rates with increasing movement complexity. There were no significant differences between the contra- and ipsilesional hand in any group. These results demonstrate that lesions in the left parietal lobe lead to a disturbed spatio-temporal organisation of movement that becomes increasingly prominent for more complex movements.

Adult↗

PubMed2001

Local Lyapunov exponents detect epileptic zones in spike-less interictal MEG recordings.

OBJECTIVE: In terms of dynamical system theory the rapid alteration of electromagnetic brain signal properties observed with transition from interictal into ictal epileptic activity implies an alteration between at least two dynamical states (attractors). We explored whether such a multistability is reflected also in the dynamical characteristics of the interictal signal. METHODS: A combined method consisting of structural MRI, multichannel magnetoencephalography (MEG) and the non-linear dynamics was applied for the detection of subthreshold interictal activity in temporal lobe epilepsy. Employing multichannel MEG we calculated local Lyapunov exponents (ILE) as a measure of the probability of state transitions in patients with mesiotemporal and extra-mesiotemporal focal epilepsy. RESULTS: The spatial distribution of the variability of ILE was found to be correlated to the side of the epileptic focus, thus, providing a reliable estimate of its localization. CONCLUSION: Our results demonstrate that interictal epileptic activity is characterized by an increase of the number of transitions between different attractors.

Adult↗