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G Deuschl

Publications and source records attributed to G Deuschl.

At least 19 recordsLinked to original sources
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

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

Dystonic tremor.

Dystonic tremor is a new and still poorly defined clinical entity. It seems to be generally accepted that tremor in the setting of obvious dystonia should be classified in this category. It may occur in generalized, segmental, and focal dystonias as well as in primary and secondary dystonias. In primary dystonia dystonic tremor may precede the occurrence of clear signs of dystonia which hence causes uncertainty about the classification of this condition. Secondary criteria like persistently focal tremor in one extremity, jerky and irregular tremors, gestes antagonistes, or selective responsiveness to antidystonic therapeutic agents may be helpful to distinguish this entity. The occurrence of dystonic tremor in symptomatic cases is often seen following thalamic lesions, peripheral injuries or in dystonia associated with sympathetic reflex dystrophy. The pathophysiology is unknown. Reciprocal inhibition and other inhibitory reflex pathways at various levels seem to be reduced at least in some cases with dystonic tremors.

Dystonia↗
PubMed2002

Dissociation of habit-learning in Parkinson's and cerebellar disease.

Damage to the medial-temporal region is known to result in declarative (explicit) memory deficits but nondeclarative (implicit) memory is largely unaffected by such lesions. Earlier studies have shown that some forms of implicit learning depend on cerebellar circuits but remain preserved following affections of the basal ganglia circuits. It is unknown which forms of implicit learning persist in patients with cerebellar pathology but are affected after basal ganglia lesions. Therefore, we determined if a test sensitive for habit-learning (probabilistic classification task) resulted in normal values for patients with cerebellar disease but resulted in affected results in patients with Parkinson's disease (PD). To this end, 23 patients with PD, 16 patients with familial or idiopathic cerebellar degeneration (CD), and 20 controls were tested for habit-learning. There was no impairment of patients with CD for the early learning period but there was abnormal learning in the PD group. For a later learning period, the patients with the PD showed improved performance. We conclude that the probabilistic learning task is an implicit, nonmotor learning task which is sensitive for basal ganglia pathology but remains unaffected in the case of cerebellar pathology. Such a test may be of special interest for the detection and possible neurobehavioral treatment of cognitive and motor deficits.

Aged↗
PubMed2002

Evaluation of healthcare utilization and health status of patients with Parkinson's disease treated with deep brain stimulation of the subthalamic nucleus.

OBJECTIVE: To assess the effects on motor functioning, health status and direct medical costs of high-frequency stimulation of the subthalamic nucleus (DBS-STN) in patients with idiopathic Parkinson's disease (PD). In addition, the cost-effectiveness of DBS-STN vs. drug treatment was investigated. METHODS: 16 consecutive patients with PD from two centers (Düsseldorf/Cologne; Kiel) treated by DBS-STN were prospectively evaluated. Clinical evaluations were done at baseline and 1, 3, 6, 12 months following surgery by means of the Unified Parkinson's disease Rating Scale (UPDRS). Health status of PD patients was assessed using the Sickness Impact Profile (SIP) at baseline and 6 months following surgery. Relevant economic data were taken from the medical records and costs (1999) were derived from different German medical economic resources. Costs were determined from the perspective of the health care provider. RESULTS: Following DBS-STN UPDRS scores (subscores and sum score) as well as health status improved considerably in PD patients. The overall SIP score and the physical dimension score (p < 0.009) were significantly different (p < 0.01) six month after surgery compared with baseline values. Mean costs of DM 40,020 (US dollars 20,810, EURO 20,410, GB pounds 12,810) per patient were spent during the 12 month observation period for in-patient and out-patient care. These expenses included already the costs for the electronic device for bilateral stimulation. Following DBS-STN medication was considerably reduced. Mean daily drug costs at baseline were DM 46.7+/-21.8 (US dollars 24, EURO 24, GB pounds 15) and DM 18.3+/-17.7 (US dollars 10, EURO 9, GB pounds 6) at 12 months following DBS-STN. Accounting for the decreased drug consumption, total annual costs amounted to DM 31,400 (US dollars 16,330, EURO 16,010, GB pounds 10,050). Further, we estimated the incremental cost effectiveness as DBS-STN had higher costs but was more effective than baseline treatment. The incremental total cost-effectiveness ratio for DBS-STN was DM 1.800 (US dollars 940, EURO 920, GB pounds 580) for one point decrease of the UPDRS. CONCLUSION: DBS-STN is an effective treatment that considerably alleviates the severity of signs and symptoms and improves the health status of patients with PD. Compared with drug treatment, however, the expenditures associated with DBS-STN are increased when only direct medical costs are considered in a one year horizon. However, on a long-term basis costs will decrease considerably because of the reduction of the drug expenditure and improved functioning in all activities of daily living. To adequately evaluate the cost-effectiveness of DBS-STN compared with standard drug regimen for PD it is necessary to include direct, indirect and intangible costs on a long-term basis and under standardized circumstances.

Aged↗
PubMed2002

Deep-brain stimulation for Parkinson's disease.

Deep brain simulation (DBS) is a powerful new therapeutic approach for patients with Parkinson's disease. However, patient selection is critical for a valuable therapeutic result. Dopa sensitivity of the target symptoms, severe disability and low neurosurgical risks are among the major criteria for this indication. Other criteria like age or cognition must still be addressed in future prospective studies. The preferred target for DBS in PD is the subthalamic nucleus for various good reasons. However, prospective studies for this procedure are lacking and some clinical problems may be more easily solved with targeting the internal pallidum or the thalamus. Despite major progress in this field, much work remains to be done.

Electric Stimulation Therapy↗
PubMed2002

Magnetic resonance imaging-based morphometry and landmark correlation of basal ganglia nuclei.

The two principle targets for deep brain stimulation or lesioning in patients with Parkinson's disease, the subthalamic nucleus (STN) and the globus pallidus internus (GPi), reveal a high degree of individual variability which is relevant to the planning of stereotactic operations. Both nuclei can clearly be delineated in T2WI spin echo MRI which was acquired under stereotactic conditions in general anesthesia before surgery. Such images of 35 patients served for retrospective morphometric analysis of different basal ganglia nuclei (STN, GP, red nucleus, and substantia nigra) and several anatomical landmarks (anterior and posterior commissure, maximum width of third ventricle, brain length and width). The average AC-PC distance was 25.74 mm (range 21 to 29 mm) and is in agreement with previous studies. On average, the center of the STN was located 12.65 mm (+/-1.3) lateral from the midline as determined 3 mm ventral to the intercommissural plane. The average width of the third ventricle was 7.05 mm (+/-2.41). The width of the third ventricle correlated with the laterality of the STN (r(right)=.78; r(left)=.83) and GP (r(right)=.76; r(left)=.68). Although to a lesser extent, significant correlations were also observed between the laterality of the STN and brain width, improving prediction of STN laterality by multiple linear regression analysis (r(right)=.82; r(left)=.87). Similarly, the laterality of GP correlated with brain width. In addition, gender-specific differences were detected. The STN and GP was located farther lateral in males which may be due to overall brain anatomy as gender-specific differences were also observed for brain width and length and AC-PC distance. MRI-based in vivo-localization of different basal ganglia nuclei extend statistical information from common histological brain atlases which are based on a limited number of brains. The correlations observed between different basal ganglia nuclei, i.e. the STN and GPi, and anatomical landmarks may be useful for surgical planning.

Adult↗
PubMed2002

Intact artificial grammar learning in patients with cerebellar degeneration and advanced Parkinson's disease.

In an artificial grammar learning task, subjects were asked to memorise short lists of letter strings formed according to complex rules for letter order. After an interval they were unexpectedly asked to discriminate new grammatical strings from strings which used the same letters but violated the sequential constraints of the grammar. Artificial grammar learning can be mastered successfully by amnesic patients and is considered to be an implicit learning task independent of declarative learning and memory mechanisms. In this study, 10 patients with cerebellar degeneration (CD), 21 Parkinson's disease (PD) and 15 control subjects were tested on artificial grammar learning. Additionally PD patients with advanced disease were examined under adequate medication and dopaminergic withdrawal. All patient groups showed intact artificial grammar learning. Neither cerebellar damage nor basal ganglia dysfunction nor dopaminergic medication impairs or affects artificial grammar learning. Although the patients showed significant executive dysfunction, implicit learning remains intact. The conclusion is that cerebellar and basal ganglia circuits play no essential part in this kind of implicit learning. The results suggest that artificial grammar learning is a cortically mediated function comparable to the mechanism of visual priming.

Aged↗
PubMed2002

Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study).

OBJECTIVES: To determine the efficacy and safety of the catechol-O-methyltransferase (COMT) inhibitor entacapone, used as an adjunct to levodopa, in Parkinson's disease (PD) patients. PATIENTS AND METHODS: In this parallel group, randomized, double-blind study, 301 PD patients, the majority with motor fluctuations, received entacapone (200 mg) or placebo with each daily dose of standard or controlled-release (CR) levodopa. The 24-week treatment period was followed by 2 weeks of entacapone withdrawal. Efficacy was determined by home diaries ('on' and 'off' times), Unified Parkinson's Disease Rating Scale (UPDRS) and changes in levodopa dosage, and safety by adverse-event inquiry, vital signs, electro cardiography (ECG) and laboratory tests. RESULTS: In the total population, the UPDRS activities of daily living and motor scores were significantly improved (P < 0.05) by entacapone vs placebo. In fluctuating patients, 'on' time increased (1.7 h) and 'off' time decreased (1.5 h) significantly more with entacapone than with placebo (0.5 and 0.6 h, respectively; P < 0.05), and the daily levodopa dose was reduced by 54 mg with entacapone and increased by 27 mg with placebo (P < 0.05). Entacapone benefit was lost on withdrawal. Entacapone efficacy was comparable between patients using CR and standard levodopa preparations. Increased dyskinesias (entacapone 34%, placebo 26%) and nausea (10 and 5%, respectively), mostly occurring shortly after treatment initiation, were generally managed by reducing the levodopa dose. Diarrhoea (entacapone 8%, placebo 4%) was seldom severe. There were no differences in vital signs, ECG or laboratory results. CONCLUSION: Entacapone is an effective and safe levodopa extender and enhancer, improving the symptomatic efficacy of levodopa in PD and adding to the patients' benefit.

Aged↗
PubMed2002

MRI- and skull x-ray-based approaches to evaluate the position of deep brain stimulation electrode contacts--a technical note.

Deep brain stimulation (DBS) has developed into an established therapy for the treatment of movement disorders, most commonly Parkinson's disease and tremor of different etiology. The subthalamic nucleus (STN) has evolved as the preferred target for DBS in patients with idiopathic Parkinson's disease. The principal target for DBS in tremor patients is the ventrolateral thalamus which has been explored for ablative procedures (thalamotomy) for some decades. Detailed information about the exact site of chronic stimulation, i.e. the location of the active electrode contacts, are important to map the actual subcortical structures modulating the therapeutic effects of DBS. We compared two different methods not requiring intra-operative teleradiography to determine the stereotactic coordinates of single electrode contacts, (i) correlation of pre- and post-operative MRI, and (ii) post-operative stereotactic skull x-ray. For seven patients implanted bilateral with quadripolar DBS electrodes the coordinates for each contact were determined by both approaches. This revealed for a total of 56 electrode contacts a median euclidean 3D-difference between both methods of 1.18 mm (range 0.42 to 1.93 mm). These data suggest that both approaches may be used to determine the position of single electrode contacts.

Electric Stimulation Therapy↗
PubMed2002

Technical complication in deep brain stimulation.

With a growing number of patients treated with deep brain stimulation (DBS) operations for both hardware-related complications and routine replacements of impulse generators will be performed more frequently. Failure of DBS systems have to be analyzed thoroughly as this thwarts the enormous efforts required for proper electrode implantation and operative revisions increase the morbidity associated with DBS. A female patient implanted with DBS electrodes for advanced Parkinson's disease presented with straining of the right extension lead and deteriorating gait because of electrode migration. This was due to a malpositioned set screw connector adapting the electrode lead to the extension wire which had been placed below the mastoid process. Following surgical revision with implantation of a new electrode into the STN, electrode dislocation recurred requiring another surgical revision. This was due to renewed connector migration from its parietal position into the cervical region. Straining of extension leads should be recognized as a warning sign for (imminent) electrode dislocation or lead fracture. This may just be the case with connectors located below the mastoid process or in the cervical region, a risk which appears to be increased further with reduced-length extensions. Renewed dislocation of revised extensions may be prevented by securing the position of the connector (e.g. with manipulates).

Electric Stimulation Therapy↗
PubMed2002

Typical features of cerebellar ataxic gait.

BACKGROUND: Although gait disturbance is one of the most pronounced and disabling symptoms in cerebellar disease (CD), quantitative studies on this topic are rare. OBJECTIVES: To characterise the typical clinical features of cerebellar gait and to analyse ataxia quantitatively. METHODS: Twelve patients with various cerebellar disorders were compared with 12 age matched controls. Gait was analysed on a motor driven treadmill using a three dimensional system. A tandem gait paradigm was used to quantify gait ataxia. RESULTS: For normal locomotion, a significantly reduced step frequency with a prolonged stance and double limb support duration was found in patients with CD. All gait measurements were highly variable in CD. Most importantly, balance related gait variables such as step width and foot rotation angles were increased in CD, indicating the need for stability during locomotion. The tandem gait paradigm showed typical features of cerebellar ataxia such as dysmetria, hypometria, hypermetria, and inappropriate timing of foot placement. CONCLUSIONS: Typical features of gait in CD are reduced cadence with increased balance related variables and an almost normal range of motion (with increased variability) in the joints of the lower extremity. The tandem gait paradigm accentuates all the features of gait ataxia and is the most sensitive clinical test.

Disability Evaluation↗
PubMed2002

Essential tremor and cerebellar dysfunction: abnormal ballistic movements.

BACKGROUND: Clinical characteristics reminiscent of cerebellar tremor occur in patients with advanced essential tremor. Ballistic movements are known to be abnormal in cerebellar disease. The hypothesis was proposed that ballistic movements are abnormal in essential tremor, reflecting cerebellar dysfunction. OBJECTIVE: To elucidate the role of the cerebellum in the pathophysiology of essential tremor. METHODS: Kinematic parameters and the triphasic electromyographic (EMG) components of ballistic flexion elbow movements were analysed in patients assigned to the following groups: healthy controls (n = 14), pure essential postural tremor (ET(PT); n = 17), and essential tremor with an additional intention tremor component (ET(IT); n = 15). RESULTS: The main findings were a delayed second agonist burst (AG(2)) and a relatively shortened deceleration phase compared with acceleration in both the essential tremor groups. These abnormalities were most pronounced in the ET(IT) group, which had additional prolongation of the first agonist burst (AG(1)) and a delayed antagonist burst (ANT). CONCLUSIONS: Abnormalities of the triphasic pattern and kinematic parameters are consistent with a disturbed cerebellar timing function in essential tremor. These abnormalities were most pronounced in the ET(IT) group. The cerebellar dysfunction in essential tremor could indicate a basic pathophysiological mechanism underlying this disorder. ET(PT) and ET(IT) may represent two expressions within a continuous spectrum of cerebellar dysfunction in relation to the timing of muscle activation during voluntary movements.

Adult↗