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Biomedical subjects

G Deuschl

Publications and source records attributed to G Deuschl.

At least 37 records · Page 2Linked to original sources
PubMed2005

Platelet activation and platelet-leucocyte interaction in patients with migraine. Subtype differences and influence of triptans.

As migraine is the result of an inflammatory mechanism with serotonergic signalling, leucocyte function, platelet function and intercellular communication between those cells is likely to be connected to the final pathway of the disease. We examined P-selectin expression on platelets (platelet activation) and leucocyte-platelet aggregate formation in 72 migraine patients during their attack-free interval and controls using a flow cytometric assay. Patients suffering from migraine without aura had a significantly increased platelet activation and leucocyte-platelet aggregation compared with the control group, unlike the migraine patients with aura. Patients who had taken a triptan within 3 days prior to the investigation showed platelet activation values similar to the control group. The variations in platelet activation patterns of migraine subgroups could indicate different pathomechanisms. Even outside an attack, migraine patients, particularly those without aura, show an increased level of platelet activation which seems to be down-regulated by triptans. This mechanism may account for the triptan-induced increases in headache frequency. The involvement of proinflammatory platelet-leucocyte cross-talk suggests a possible therapeutic strategy using anti-inflammatory drugs.

Female↗
PubMed2004

The effect of subthalamic nucleus stimulation on autogenic inhibition in Parkinson disease.

BACKGROUND: Recent animal experiments suggest an important role of descending input from basal ganglia to brainstem and via the reticulospinal tract (RST) to spinal cord in the genesis of motor symptoms in Parkinson disease (PD). In humans, a marker for RST activity is Ib mediated autogenic inhibition, which is reduced in PD patients. The authors investigated the effect of high frequency stimulation of the subthalamic nucleus (STN-HFS) on autogenic inhibition in PD. METHODS: In 10 controls and 10 PD patients with chronically implanted STN electrodes, the soleus H-reflex conditioned by gastrocnemius nerve stimulation (interstimulus interval 2 to 10 msec) was used to examine the effect of STN-HFS on the activity of Ib spinal interneurons. RESULTS: STN-HFS was able to restore the abnormally reduced autogenic inhibition. The H-reflex changes during STN-HFS significantly correlated with the clinical improvement of gait and posture. CONCLUSIONS: Observed changes in spinal autogenic inhibition may allow measurement of the contribution of subcortical routes to the STN-HFS induced motor benefit in PD.

Aged↗
PubMed2004

Two different pathogenetic mechanisms in psychogenic tremor.

BACKGROUND: The pathophysiologic mechanism underlying psychogenic tremor is not clear. Continuous voluntary production of tremor may be uncovered by a positive entrainment of tremor in different limbs. But some patients have tremor ongoing during their waking time which is unlikely to be produced voluntarily. Therefore, nonvoluntary physiologic oscillatory mechanisms must be considered. METHODS: Fifteen patients with psychogenic tremor manifesting in both hands, who were diagnosed using established criteria, were examined. Postural tremor was recorded with accelerometry and electromyography (EMG) while the hands were held against gravity. Power spectral peak frequencies and accelerometric total power as a measure of amplitude were determined. Coherency spectra between the EMG signals from the right and left arm were calculated. RESULTS: Seven of 15 patients showed a significant coherency between the two hands; the remaining 8 patients maintained independent oscillations. Clinical presentation, tremor frequencies, and amplitudes were not significantly different between the two groups. CONCLUSIONS: Two different pathogenetic mechanisms may play a role in psychogenic tremor. Bilateral voluntary movements are typically coherent. Thus, coherent psychogenic tremor would be in keeping with voluntarily produced oscillations. Absent coherence is an indication of another, possibly nonvoluntary mechanism like clonus or enhanced physiologic tremor.

Adult↗
PubMed2004

High concordance for essential tremor in monozygotic twins of old age.

OBJECTIVE: To assess the relative contribution of genetic and environmental factors for the etiology of essential tremor (ET) and to explore the effect of different diagnostic criteria. METHODS: A total of 2,448 twins of the Danish twin registry aged 70 years or more were screened for ET by an interview and an Archimedes spiral test. All twin pairs (n = 162) with a positive screening test of at least one of the twins were recontacted and 218 individuals (109 pairs) were interviewed and examined by a movement disorder specialist. The consensus criteria of the Tremor Investigation Group were applied to diagnose ET. RESULTS: Twenty-nine twins fulfilled the criteria of definite, 7 of probable, and 56 of possible ET. The probandwise concordance rate for the broadest definition of ET was 77% for monozygotic twins (MZ) and 59% for dizygotic twins (DZ). However, in an analysis restricted to cases of probable and definite ET, the concordance rates were 93% and 29%. The heritability for the liability to ET ranged from 93% to 99% using a general population prevalence of 1.2% for white 70+-year-olds. The inclusion of probable and exclusion of possible cases in the diagnosis of ET produced the highest concordance rates. CONCLUSION: The high concordance among MZ twins of very old age in this first population-based twin study of ET suggests that a disease phenotype consisting of definite and probable ET has a high heritability and hence is a good candidate for a phenotype to be used in linkage studies.

Age Factors↗
PubMed2004

Gait analysis of sporadic and hereditary spastic paraplegia.

OBJECTIVES: Sporadic (SSP) and hereditary spastic paraplegias (HSP) are clinically and genetically heterogeneous disorders, which are characterised by a slowly progressive spastic paraparesis. Initial symptoms and the rate of progression are variable even among members of the same family. Spastic paraparesis is the major and most disabling clinical symptom and was assessed with gait analysis using a three-dimensional infrared movement analysis system. METHODS AND RESULTS: 22 patients with clinically and/or genetically confirmed SSP/HSP were compared with age-matched control subjects. Significantly lower values were found for gait velocity, stride length, step height and the range of motion of the knee-angle. The gait pattern is characterised by a severe spasticity of both legs with only mild paresis. The balance-related gait parameters show a broad-based gait without inwardly rotated feet. No correlation was found between disease duration and the severity of the gait disorder and the central motor conduction time to the leg muscles and the abnormal gait parameters. The gait pattern did not differ between the 7 SSP cases and the 15 HSP cases. CONCLUSIONS: We conclude that three-dimensional gait analysis can uncover specific features of such rare gait disorders, and may be used as an objective tool to quantify the impairment of gait parameters in patients with SSP/HSP and thus can be used to monitor disease progression and the effect of therapeutic interventions.

Adult↗
PubMed2004

[Antidepressants and anticonvulsive agents. Practical utility profile in pain therapy].

Antidepressants are used in the treatment of neuropathic pain syndromes, as prophylaxis for primary headache syndromes, and in the treatment of fibromyalgia. Anticonvulsants are suited for therapy of all neuropathic pain syndromes, and can be applied as the method of second choice for certain headache syndromes. All substances tested with good results are tricyclic antidepressants. Their psychotropic action profile should be taken into consideration when planning therapy. Their antidepressive effect does not coincide with the effect of pain reduction. Therapy should start with a slow increase of the dose and can be prolonged as monotherapy or in combination with other analgetics. Carbamazepine is used in the treatment of shooting neuralgic pain attacks, whereas gabapentin has become the agent of first choice in the therapy of permanent neuropathic pain. Other substances in this group should be reserved for extraordinary situations based on their license and side effect profile.

Anticonvulsants↗
PubMed2004

Tremor analysis in two normal cohorts.

OBJECTIVE: Quantitative tremor analyses using almost identical methods were compared between two independent large normal cohorts, to separate robust measures that may readily be used diagnostically from more critical ones needing lab-specific normalization. METHODS: Hand accelerometry and surface EMG from forearm flexors and extensors were recorded with (500 and 1000 g) and without weight loading under postural conditions in 117 and 67 normal volunteers in two different specialty centers for movement disorders in Germany. RESULTS: Tremor amplitude (total power) and frequency fell within a similar range but differed significantly. A significant reduction of tremor frequency under 1000 g weight load (>1 Hz), and a lack of rhythmic EMG activity at the tremor frequency in around 85-90% of the recordings were robust findings in both centers. CONCLUSIONS: The differences in frequency and total power indicate that these measures critically depend on the details of the recording conditions being slightly different between the two centers. Thus each lab needs to establish its own normative data. We estimate that at least 25 normal subjects have to be recorded to obtain normal values. The reduction of tremor frequency under load and lacking tremor-related EMG activity were well reproducible allowing a differentiation of physiological from low amplitude pathological tremor. SIGNIFICANCE: This study provides a framework for more standardized tremor analyses in clinical neurophysiology.

Adult↗
PubMed2004

Platelet-leukocyte interaction and platelet activation in migraine: a link to ischemic stroke?

OBJECTIVES: Migraine has been identified as an independent risk factor for ischemic stroke. Both neurogenic inflammation and platelet activation have been linked to the pathophysiology of migraine. Increased platelet activation results in up-regulation of specific binding to leukocytes which promotes pro-inflammatory leukocyte secretion and their tethering to endothelium, a mechanism that has been demonstrated in stroke and which could provide a link to migraine. We aimed to determine whether platelet-leukocyte aggregation is increased in migraine patients outside an acute attack. METHODS: Seventy two patients with migraine according to IHS criteria were compared to a control group (n = 72). Whole blood flow cytometry was used to quantify the activation dependent P selectin on the platelet, and to assess the fraction of platelets bound to the different leukocyte subsets. RESULTS: Migraine patients showed significantly more platelet-leukocyte aggregates compared to the control subjects (p = 0.003). This effect was driven by an increased polymorphonuclear cell-platelet aggregation (p = 0.003) whereas platelet aggregation with monocytes and lymphocytes was not. Platelet activation was also increased (p = 0.001). CONCLUSIONS: In migraine pro-inflammatory platelet adhesion to leukocytes occurs during the headache free interval similar to that seen in acute coronary and cerebrovascular syndromes. This may suggest a link between migraine and stroke on a cellular level.

Acute Disease↗
PubMed2004

Probable multiple system atrophy in a German family.

Multiple system atrophy (MSA) is a neurodegenerative disorder of unknown aetiology. A possible underlying genetic component has not yet been identified. A family is reported with phenotypic MSA and probable autosomal dominant inheritance. The patients presented initially with either parkinsonian or cerebellar signs, and developed severe autonomic failure and typical atrophy of the brain stem and cerebellum in the course of the disease.

Adult↗
PubMed2003

Rate dependency of the human cortical network subserving executive functions during generation of random number series--a functional magnetic resonance imaging study.

In a random number generation (RNG) task subjects are instructed to generate the numbers 1-10 in a random fashion. RNG performance is assumed to involve executive functions, as it requires controlled response generation and suppression of habitual responses. To investigate cerebral structures involved in RNG associated executive functions we investigated functional magnetic resonance imaging in eight healthy subjects while performing an RNG task at two different response rates (1 and 2 Hz). During the 1 Hz condition an activation was detected bilaterally in the dorsolateral prefrontal cortex (BA 9/46), the lateral premotor cortex (BA 6), the anterior cingulate (BA 32), the inferior and superior parietal cortex (BA 7/40) and the cerebellar hemispheres. In the 2 Hz condition behavioural data showed higher counting tendencies reflecting poorer executive control. In parallel, a homogenous diminution of the activity in the involved cortical areas was obtained. This finding would support the theory of a cortical network involved in executive functions consisting of distinct brain regions working together rather than a distinct fronto-cortical functional localisation.

Adult↗
PubMed2003

The phenylalanine loading test in the differential diagnosis of dystonia.

Early diagnosis of dopa-responsive dystonia (DRD) and its delineation from other dystonic syndromes is of great relevance because DRD is an eminently treatable condition. The possible relevance of the phenylalanine loading test (Phe-L) in differentiating DRD from primary focal and generalized dystonia was investigated. A marked difference in the phenylalanine/tyrosine ratio between patients with DRD and patients with other types of dystonia was observed. This indicates that Phe-L may be helpful in the differential diagnosis of dystonias.

Administration, Oral↗
PubMed2003

Deep brain stimulation of the subthalamic nucleus for Parkinson's disease: a therapy approaching evidence-based standards.

DBS of the STN is one of the most promising new therapies for the treatment of PD. However - like many other therapies for PD - the present stage of the scientific assessment does not yet suffice the rigid criteria of evidence-based medicine. Further studies should specifically address the questions of efficacy and side effects as well as the impact on quality of life.

Dyskinesias↗
PubMed2003

Intrathecal synthesis of monocyte chemoattractant protein-1 (MCP-1) in amyotrophic lateral sclerosis: further evidence for microglial activation in neurodegeneration.

Autopsy studies and animal experiments suggest that microglial inflammation contributes to the pathogenesis of amyotrophic lateral sclerosis (ALS). Monocyte-chemoattractant protein (MCP-1) might play an important role in microglial recruitment. We studied MCP-1 levels in sera and cerebrospinal fluid of 29 ALS patients and compared the results with 11 control patients with tension headache. The MCP-1 level was determined using enzyme-linked immunosorbent assays (ELISA). A significant increase in cerebrospinal fluid MCP-1 level but not serum level was seen in the patients with ALS compared to the control subjects. These results suggest that cerebrospinal fluid MCP-1 activity may be a sensitive marker for neuroinflammation in ALS useful for monitoring treatment trials in ALS.

Age of Onset↗
PubMed2003

Involvement of benzodiazepine receptors in neuroinflammatory and neurodegenerative diseases: evidence from activated microglial cells in vitro.

Increased binding of a ligand for the peripheral benzodiazepine binding receptor is currently used in PET studies as an in vivo measurement of inflammation in diseases like multiple sclerosis and Alzheimer's disease. Although peripheral-type benzodiazepin receptors (PBRs) are abundant in many cell types and expressed in the CNS physiologically only at low levels, previous reports suggest that after experimental lesions in animal models and in human neurodegenerative/-inflammatory diseases upregulated PBR expression with increased binding of its ligand PK11195 is confined mainly to activated microglia in vivo/in situ. Because the functional role of the PBR is unknown, we confirm by immunohistochemistry and PCR (I) that this receptor is expressed on microglia in vitro and (II) that benzodiazepines modulate proliferation of microglial cells and the release of the inflammatory molecules nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) in cell culture supernatants of primary rat microglia. Compared to lipopolysaccharide-activated controls the release of NO was markedly decreased in cultures treated with benzodiazepines (clonazepam, midazolam, diazepam) and the PBR ligand PK11195. Moreover, release of TNF-alpha and proliferation was significantly inhibited in the benzodiazepine-treated groups. These findings link the in vivo data of elevated PBR levels in neurodegenerative/-inflammatory diseases to a functional role and opens up possible therapeutic intervention targeting the PBR in microglia.

Animals↗
PubMed2003

Eye movement abnormalities in essential tremor may indicate cerebellar dysfunction.

Experimental and clinical data indicate that the cerebellum is involved in the pathophysiology of advanced stages of essential tremor (ET). The aim of this study was to determine whether a dysfunction also affects cerebellar structures involved in eye movement control. Eye movements of 14 patients with ET and 11 age-matched control subjects were recorded using the scleral search-coil technique. Vestibular function was assessed by electro-oculography. Eight ET patients had clinical evidence of intention tremor (ET(IT)); six had a predominantly postural tremor (ET(PT)) without intention tremor. ET patients showed two major deficits that may indicate cerebellar dysfunction: (i) an impaired smooth pursuit initiation; and (ii) pathological suppression of the vestibulo-ocular reflex (VOR) time constant by head tilts ('otolith dumping'). In the step ramp smooth pursuit paradigm, the initial eye acceleration in the first 60 ms of pursuit generation was significantly reduced in ET patients, particularly in ET(IT) patients, by approximately 44% (mean 23.4 degrees/s(2)) compared with that of control subjects (mean 41.3 degrees/s(2)). Subsequent steady-state pursuit velocity and sinusoidal pursuit gain (e.g. 0.4 Hz: 0.90 versus 0.78) were also significantly decreased in ET patients, whereas pursuit latency was unaffected. The intention tremor score correlated with the pursuit deficit, e.g. ET(IT) patients were significantly more affected than ET(PT) patients. Gain and time constant (tau) of horizontal VOR were normal, but suppression of the VOR time constant by head tilt ('otolith dumping') was pathological in 41% of ET patients, particularly in ET(IT) patients. Saccades and gaze-holding function were not impaired. The deficit of pursuit initiation, its correlation with the intensity of intention tremor, and the pathological VOR dumping provide additional evidence of a cerebellar dysfunction in the advanced stage of ET, when intention tremor becomes part of the clinical symptoms, and point to a common pathomechanism. The oculomotor deficits may indicate an impairment of the caudal vermis in ET.

Adult↗
PubMed2003

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: evaluation of active electrode contacts.

BACKGROUND: The subthalamic nucleus is the preferred target for deep brain stimulation in patients with advanced Parkinson's disease. The site of permanent stimulation is the subject of ongoing debate, as stimulation both within and adjacent to the subthalamic nucleus may be effective. OBJECTIVE: To assess the position of active electrode contacts in relation to the dorsal margin of the subthalamic nucleus as determined by intraoperative microrecordings and magnetic resonance imaging (MRI). METHODS: In 25 patients suffering from severe levodopa sensitive parkinsonism, deep brain stimulating electrodes (n = 49) were implanted following mapping of the subthalamic nucleus by microrecording and microstimulation along five parallel tracks. Postoperative stereotactic radiography and fusion of pre- and postoperative MRI studies were used to determine the stereotactic position relative to the midcommissural point of the most effective electrode contacts selected for permanent stimulation (n = 49). Intraoperative microrecordings were analysed retrospectively to define the dorsal margin of the subthalamic nucleus. In cases where the dorsal margin could be defined in at least three microrecording tracks (n = 37) it was correlated with the position of the active contact using an algorithm developed for direct three dimensional comparisons. RESULTS: Stimulation of the subthalamic nucleus resulted in marked improvement in levodopa sensitive parkinsonian symptoms and levodopa induced dyskinesias, with significant improvement in UPDRS III scores. In several instances, projection of the electrode artefacts onto the T2 weighted MRI visualised subthalamic nucleus of individual patients suggested that the electrodes had passed through the subthalamic nucleus. When the actual position of active electrode contacts (n = 35) was correlated with the dorsal margin of the subthalamic nucleus as defined neurophysiologically, most contacts were located either in proximity (+/- 1.0 mm) to the dorsal border of the subthalamic nucleus (32.4%) or further dorsal within the subthalamic region (37.8%). The other active contacts (29.7%) were detected within the dorsal (sensorimotor) subthalamic nucleus. The average position of all active contacts (n = 49) was 12.8 mm (+/- 1.0) lateral, 1.9 mm (+/- 1.4) posterior, and 1.6 mm (+/- 2.1) ventral to the midcommissural point. CONCLUSIONS: Subthalamic nucleus stimulation appears to be most effective in the border area between the upper subthalamic nucleus (sensorimotor part) and the subthalamic area containing the zona incerta, fields of Forel, and subthalamic nucleus projections.

Aged↗
PubMed2003

Subthalamic nucleus stimulation in Parkinson's disease: correlation of active electrode contacts with intraoperative microrecordings.

BACKGROUND/AIMS: The most effective site for subthalamic nucleus (STN) stimulation has remained unclear. The position of active contacts relative to the dorsal margin of the STN was determined. METHODS: Electrodes (n = 49) were implanted following STN mapping by microrecording and microstimulation along five tracks (n = 25 patients). The stereotactic position of active contacts was determined and correlated with microrecordings using an algorithm for direct three-dimensional comparisons (n = 37). RESULTS: Most active contacts were detected within +/-1.0 mm from the dorsal margin of the STN as defined by microrecording (32.4%) or farther dorsal in the subthalamic area (37.8%), and only 29.7% were localized to the STN proper. This was consistent with the average stereotactic coordinates of the active contacts in these three groups. CONCLUSION: Our data suggest that the dorsal border area of the STN is the most effective target. Besides the dorsolateral STN (sensorimotor part) this may include projections from/to STN, the zona incerta, and pallidofugal projections in the fields of Forel.

Electric Stimulation Therapy↗