Search PubMed⌕ Search

Biomedical subjects

Günther Deuschl

Publications and source records attributed to Günther Deuschl.

At least 19 recordsLinked to original sources

How to assess motor impairment in writer's cramp.

Writer's cramp is a task-specific hand dystonia affecting handwriting. Clinical scores such as the Arm Dystonia Disability Scale (ADDS) or Writer's Cramp Rating Scale (WCRS) as well as kinematic analysis of handwriting movements have been used to assess functional impairment in affected patients. In 21 patients with writer's cramp and healthy controls, we analyzed the kinematics of writing and cyclic drawing movements. We rated the severity of dystonia using the ADDS and WCRS and correlated the clinical scores with movement kinematics. Mean stroke frequency was significantly reduced in dystonic patients. Drawing movements showed more frequently a decrease in stroke frequency than handwriting movements. During circle drawing, mean vertical peak velocity was more variable in patients relative to controls, indicating an impaired ability to reproduce the same kinematic pattern over time. An increase in vertical writing pressure was only observed during handwriting but not during circle drawing and may reflect a compensatory effort to stabilize the pencil. Kinematic measures and individual ADDS and WCRS scores did not correlate with each other. The lack of correlation is not surprising as ADDS, WCRS, and kinematic analysis probe different aspects of motor impairment. The ADDS characterizes how dystonia affects a set of fine manual tasks, whereas the WCRS scores the manifestation of dystonia during handwriting. Therefore, the clinical scores and kinematic analysis of handwriting provide complementary insights into motor impairment. Future studies need to address which combination of clinical scores and kinematic measures are most appropriate to quantify impairment in writer's cramp.

Adult↗

Lp(a) lipoprotein and plasminogen activity in patients with different etiology of ischemic stroke.

BACKGROUND AND PURPOSE: Lp(a) lipoprotein plays an important part in atherothrombogenesis and is considered an independent risk factor for coronary heart disease. However, its role in cerebrovascular disease remains unclear, in particular because of the heterogeneous nature of strokes. We investigated whether elevated Lp(a) is more frequent in ischemic stroke related to atherothrombosis than in other etiologies of stroke. Because of the close structural homology between Lp(a) and plasminogen, we also studied the role of plasminogen in different stroke subtypes and whether there is a dependency on Lp(a) plasma levels. METHODS: Lp(a) levels and plasminogen activity were measured in 253 consecutive patients with acute ischemic stroke and in 63 controls (CS). Subtypes of stroke were established according to the TOAST criteria. RESULTS: Median Lp(a) levels were found to be higher in the total cerebral infarction group and in patients with large artery atherosclerosis (LAA) when compared with CS (20.9 and 22.0 mg/dl, respectively, vs. 16.0 mg/dl; p < 0.05). In addition, elevated Lp(a) levels >30 mg/dl were more frequent among the LAA subgroup than among CS (39.4 vs. 11.1%; p < 0.001). Mean plasminogen activity was lower in the total cerebral infarction group (110.8 vs. 120.3%; p < 0.001) and in patients with cardioembolic stroke (109.8 vs. 120.3%; p < 0.05) when compared with CS. There was no correlation between Lp(a) levels and plasminogen activity. CONCLUSIONS: Our results support the hypothesis that elevated Lp(a) is a risk factor for ischemic stroke and especially for strokes caused by LAA. Low plasminogen activity may play a role in the pathogenesis of cerebrovascular disease, especially for the development of cardioembolic stroke.

Acute Disease↗

Pallidal deep-brain stimulation in primary generalized or segmental dystonia.

BACKGROUND: Neurostimulation of the internal globus pallidus has been shown to be effective in reducing symptoms of primary dystonia. We compared this surgical treatment with sham stimulation in a randomized, controlled clinical trial. METHODS: Forty patients with primary segmental or generalized dystonia received an implanted device for deep-brain stimulation and were randomly assigned to receive either neurostimulation or sham stimulation for 3 months. The primary end point was the change from baseline to 3 months in the severity of symptoms, according to the movement subscore on the Burke-Fahn-Marsden Dystonia Rating Scale (range, 0 to 120, with higher scores indicating greater impairment). Two investigators who were unaware of treatment status assessed the severity of dystonia by reviewing videotaped sessions. Subsequently, all patients received open-label neurostimulation; blinded assessment was repeated after 6 months of active treatment. RESULTS: Three months after randomization, the change from baseline in the mean (+/-SD) movement score was significantly greater in the neurostimulation group (-15.8+/-14.1 points) than in the sham-stimulation group (-1.4+/-3.8 points, P<0.001). During the open-label extension period, this improvement was sustained among patients originally assigned to the neurostimulation group, and patients in the sham-stimulation group had a similar benefit when they switched to active treatment. The combined analysis of the entire cohort after 6 months of neurostimulation revealed substantial improvement in all movement symptoms (except speech and swallowing), the level of disability, and quality of life, as compared with baseline scores. A total of 22 adverse events occurred in 19 patients, including 4 infections at the stimulator site and 1 lead dislodgment. The most frequent adverse event was dysarthria. CONCLUSIONS: Bilateral pallidal neurostimulation for 3 months was more effective than sham stimulation in patients with primary generalized or segmental dystonia. (ClinicalTrials.gov number, NCT00142259 [ClinicalTrials.gov].).

Adult↗

Subthalamic stimulation modulates cortical control of urinary bladder in Parkinson's disease.

Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for off-period motor symptoms and dyskinesias in advanced Parkinson's disease. Clinical studies have shown that STN-DBS also ameliorates urinary bladder function in Parkinson's disease patients by delaying the first desire to void and increasing bladder capacity. This study aimed at investigating the effect of STN-DBS on the neural mechanisms underlying cerebral bladder control. Using PET to measure changes in regional cerebral blood flow (rCBF), 11 patients with bilateral STN-DBS were studied during urodynamic bladder filling in STN-DBS ON and OFF condition. A filled bladder led to a significant increase of rCBF in the anterior cingulate cortex, which was further enhanced during STN-DBS OFF. A significant interaction between bladder state and STN-DBS was observed in lateral frontal cortex with increased rCBF when the bladder was filled during STN-DBS OFF. The data suggest that STN-DBS ameliorates bladder dysfunction and that this modulation may result from facilitated processing of afferent bladder information.

Adult↗

A randomized trial of deep-brain stimulation for Parkinson's disease.

BACKGROUND: Neurostimulation of the subthalamic nucleus reduces levodopa-related motor complications in advanced Parkinson's disease. We compared this treatment plus medication with medical management. METHODS: In this randomized-pairs trial, we enrolled 156 patients with advanced Parkinson's disease and severe motor symptoms. The primary end points were the changes from baseline to six months in the quality of life, as assessed by the Parkinson's Disease Questionnaire (PDQ-39), and the severity of symptoms without medication, according to the Unified Parkinson's Disease Rating Scale, part III (UPDRS-III). RESULTS: Pairwise comparisons showed that neurostimulation, as compared with medication alone, caused greater improvements from baseline to six months in the PDQ-39 (50 of 78 pairs, P=0.02) and the UPDRS-III (55 of 78, P<0.001), with mean improvements of 9.5 and 19.6 points, respectively. Neurostimulation resulted in improvements of 24 to 38 percent in the PDQ-39 subscales for mobility, activities of daily living, emotional well-being, stigma, and bodily discomfort. Serious adverse events were more common with neurostimulation than with medication alone (13 percent vs. 4 percent, P<0.04) and included a fatal intracerebral hemorrhage. The overall frequency of adverse events was higher in the medication group (64 percent vs. 50 percent, P=0.08). CONCLUSIONS: In this six-month study of patients under 75 years of age with severe motor complications of Parkinson's disease, neurostimulation of the subthalamic nucleus was more effective than medical management alone. (ClinicalTrials.gov number, NCT00196911 [ClinicalTrials.gov].).

Activities of Daily Living↗

The impact of normal aging and Parkinson's disease on response preparation in task-switching behavior.

This study investigates the ability to use foreknowledge in preparation of cognitive processes in young and older participants and in PD patients. Additionally, we test the hypothesis that age-associated cognitive deficits in task switching reflect a dopaminergic dysfunction that accompanies healthy aging. To this end, we use a task-switching paradigm that (i) is known to be highly sensitive for dopaminergic dysfunction in the frontostriatal loops and (ii) can be applied with predictable and unpredictable switch and non-switch trials to assess the effect of task foreknowledge. Our results show that young participants benefit from foreknowledge and are thus able to prepare for predictable cognitive processes. Older participants have lost their ability to benefit from foreknowledge, which seems to be an effect of healthy aging. In predictable trials, the performance of PD patients did not differ from that of controls. Thus, PD patients do not show an additional deficit in the preparation of predictable cognitive switches. However, PD patients are specifically impaired in unpredictable trials compared to controls. We suggest that this result can be explained by the uncertainty about the next task in the unpredictable condition which prevents an automatic process and demands more attention. Furthermore, our results of older participants do not resemble the deficits seen in PD patients in task-switching behavior. This argues for different mechanisms that underlie the changes in task-switching behavior in healthy aging and PD.

Adult↗

Tremor amplitude is logarithmically related to 4- and 5-point tremor rating scales.

Tremor rating scales (TRSs) are used commonly in the clinical assessment of tremor, but the relationship of a TRS to actual tremor amplitude has never been quantified. Consequently, the resolution of these scales is unknown, and the clinical significance of a 1-point change in TRS is uncertain. We therefore sought to determine the change in tremor amplitude that corresponds to a 1-point change in a typical 5-point TRS. Data from five laboratories were analysed, and 928 patients with various types of hand tremor were studied. Hand tremor was quantified with a graphics tablet in three different labs, an accelerometer in three labs and a mechanical-linkage device in one lab. Tremor in writing, drawing, horizontal posture, rest and finger-nose testing was graded using a variety of TRSs. The relationship between TRS scores and tremor amplitude was computed for each task and laboratory. A logarithmic relationship between a 5-point (0-4) TRS and tremor amplitude (T, measured in centimetres) was found in all five labs, despite widely varying rating scales and transducer methodology. Thus, T2/T1 = 10(alpha(TRS2-TRS1)). The value of alpha ranged from 0.414 to 0.441 for writing, 0.355-0.574 for spiral drawing, 0.441 to 0.488 for rest tremor, 0.266-0.577 for postural tremor and 0.306 for finger-nose testing. For alpha = 0.3, 0.4, 0.5, 0.6 and 0.7, the ratios T2/T1 for a 1-point decrease in TRS are 0.501, 0.398, 0.316, 0.251 and 0.200. Therefore, a 1-point change in TRS represents a substantial change in tremor amplitude. Knowledge of the relationship between TRS and precise measures of tremor is useful in interpreting the clinical significance of changes in TRS produced by disease or therapy.

Adolescent↗

Patients with Parkinson's disease learn to control complex systems-an indication for intact implicit cognitive skill learning.

Implicit memory and learning mechanisms are composed of multiple processes and systems. Previous studies demonstrated a basal ganglia involvement in purely cognitive tasks that form stimulus response habits by reinforcement learning such as implicit classification learning. We will test the basal ganglia influence on two cognitive implicit tasks previously described by Berry and Broadbent, the sugar production task and the personal interaction task. Furthermore, we will investigate the relationship between certain aspects of an executive dysfunction and implicit learning. To this end, we have tested 22 Parkinsonian patients and 22 age-matched controls on two implicit cognitive tasks, in which participants learned to control a complex system. They interacted with the system by choosing an input value and obtaining an output that was related in a complex manner to the input. The objective was to reach and maintain a specific target value across trials (dynamic system learning). The two tasks followed the same underlying complex rule but had different surface appearances. Subsequently, participants performed an executive test battery including the Stroop test, verbal fluency and the Wisconsin card sorting test (WCST). The results demonstrate intact implicit learning in patients, despite an executive dysfunction in the Parkinsonian group. They lead to the conclusion that the basal ganglia system affected in Parkinson's disease does not contribute to the implicit acquisition of a new cognitive skill. Furthermore, the Parkinsonian patients were able to reach a specific goal in an implicit learning context despite impaired goal directed behaviour in the WCST, a classic test of executive functions. These results demonstrate a functional independence of implicit cognitive skill learning and certain aspects of executive functions.

Aged↗

Time delay and partial coherence analyses to identify cortical connectivities.

Recently it has been demonstrated by Albo that partial coherence analysis is sensitive to signal to noise ratio (SNR) and that it will always identify the signal with the highest SNR among the three signals as the main (driving) influence. We propose to use time delay analysis in parallel to partial coherence analysis to identify the connectivities between the multivariate time series. Both are applied to a theoretical model (used by Albo) to analyse the connections introduced in the model. Time delay analysis identifies the connections correctly. We also apply these analyses to the electroencephalogram (EEG) and electromyogram of essential tremor patients and EEG of normal subjects while bimanually tapping their index fingers. Biologically plausible cortico-muscular and cortico-cortical connections are identified by these methods.

Algorithms↗

Subthalamic nucleus influences spatial orientation in extra-personal space.

While the role of frontal and parietal cortex in spatial orientation has been studied extensively, the contribution of the basal ganglia and especially the subthalamic nucleus to spatial orientation remains less clear. Here we use subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) as a reversible model of functional lesioning to evaluate the influence of the STN in extra-personal space orientation. To this end, 12 PD patients were examined 1 year after implantation of DBS electrodes in the STN after overnight withdrawal of L-dopa. Patients were tested in a pseudo-randomized order while both stimulators, the right only, the left only, or no stimulator, were switched on. Patients performed line bisection and a reaction time task responding to stimuli of the middle, the left, and the right extra-personal space. A separate assessment of the right and left hand responding to visual stimuli in each hemispace made it possible to distinguish hemi-spatial and hemi-motor impairments. No asymmetries in space orientation were found when both stimulators were switched OFF, when both stimulators were switched ON, and when only the right stimulator was switched ON. When only the left subthalamic stimulation was switched ON, the reaction times of both hands to visual stimuli in the left extra-personal hemispace increased significantly and the line bisection test showed a significant orientation to the right. These results lead to the conclusion that the STN and its cortical projections influence the network involved in visuospatial orientation. These patterns of symptoms of neglect demonstrate the influence of the STN on the attentional system of the nondominant hemisphere.

Attention↗

Eye-hand coordination in essential tremor.

Patients with essential tremor (ET) or with cerebellar lesions have in common oculomotor abnormalities, with the exception of saccadic eye movements, which do not seem to be involved in ET. Since grasping is prolonged in ET and might be related to saccadic dysmetria, we tested whether simultaneous hand pointing could unmask it. Twelve ET patients and 14 controls performed saccades with and without simultaneous pointing movements to the same targets, and with and without a gap between the disappearance of the fixation point and the appearance of the target. Eye movements were recorded with the magnetic search-coil method, hand movements with an ultrasound-emitting probe. ET patients did not have saccadic dysmetria, and contrary to normal subjects their saccadic latency did not decrease during combined eye-hand movements compared with saccades performed in isolation. Hand movements had a longer duration in ET patients, with decreased peak acceleration, an increased latency of the peak velocity, and peak deceleration. In conclusion, this first study on eye-hand coordination in ET revealed abnormal kinematic changes in the early phase of pointing movements. These changes might be related to cerebellar disease but they are independent of the intention tremor component and saccade performance.

Adult↗

Health-related quality of life in multiple system atrophy.

Although multiple system atrophy (MSA) is a neurodegenerative disorder leading to progressive disability and decreased life expectancy, little is known about patients' own evaluation of their illness and factors associated with poor health-related quality of life (Hr-QoL). We, therefore, assessed Hr-QoL and its determinants in MSA. The following scales were applied to 115 patients in the European MSA-Study Group (EMSA-SG) Natural History Study: Medical Outcome Study Short Form (SF-36), EQ-5D, Beck Depression Inventory (BDI), Mini-Mental state examination (MMSE), Unified MSA Rating Scale (UMSARS), Hoehn & Yahr (H&Y) Parkinson's disease staging scale, Composite Autonomic Symptom Scale (COMPASS), and Parkinson's Disease Sleep Scale (PDSS). Forty-six percent of patients had moderate to severe depression (BDI > or = 17); Hr-QoL scores on the SF-36 and EQ-5D were significantly impaired. Pain, the only domain with similar scores in MSA and published PD patients, was reported more frequently in patients with MSA-P (predominantly parkinsonian motor subtype) than MSA-C (predominantly cerebellar motor subtype; 76% vs. 50%; P = 0.005). Hr-QoL scores correlated most strongly with UMSARS motor, COMPASS, and BDI scores but not with MMSE scores, age at onset, or disease duration. The COMPASS and UMSARS activities of daily living scores were moderate-to-strong predictors for the SF-36 physical summary score and the BDI and UMSARS motor scores for the SF-36 mental summary score. This report is the first study to show that Hr-QoL is significantly impaired in MSA. Although not all possible factors related to impaired Hr-QoL in MSA could be assessed, autonomic dysfunction, motor impairment, and depression were most closely associated with poor Hr-QoL, and therapeutic management, therefore, should concentrate upon these aspects of the disease.

Anxiety↗

Quality of life and personality in essential tremor patients.

The aim of this study was to determine the impact of essential tremor (ET) on quality of life and its relation with tremor severity and the personality profile of ET patients. One hundred and five patients with definite or probable ET from an outpatient population were tested with the Short-Form 36-Item Health Survey (SF36) and the Eysenck Personality Questionnaire (EPQ-R). Compared to controls, the ET patients scored worse in all eight domains of the SF36. The physical component score (PCS) did not differ significantly from the normal population, whereas ET patients older than 40 years were significantly more affected with regard to the mental domains measured by the mental component score (MCS) with their median below the 20th percentile of the German controls. Tremor severity correlated with some of the physical domains and the PCS as well as with social function of the mental domains. ET patients showed significantly lower scores in the psychoticism (P) scale of the EPQ-R, with a median value on the 11th percentile of normal German population, indicating a more tender-minded personality type. The MCS correlated highly significant with the neuroticism (N) scale and extraversion (E) scale of EPQ-R. Multiple regression analysis identified age as the only predictive factor for the PCS and the N-scale as the only predictive factor for the MCS. Although ET is considered a pure movement disorder, the mental components of quality of life are more affected than the physical dimensions. A more controlled personality type may in part contribute to this.

Adult↗

Deep brain stimulation: postoperative issues.

Numerous factors need to be taken into account when managing a patient with Parkinson's disease (PD) after deep brain stimulation (DBS). Questions such as when to begin programming, how to conduct a programming screen, how to assess the effects of programming, and how to titrate stimulation and medication for each of the targeted sites need to be addressed. Follow-up care should be determined, including patient adjustments of stimulation, timing of follow-up visits and telephone contact with the patient, and stimulation and medication conditions during the follow-up assessments. A management plan for problems that can arise after DBS such as weight gain, dyskinesia, axial symptoms, speech dysfunction, muscle contractions, paresthesia, eyelid, ocular and visual disturbances, and behavioral and cognitive problems should be developed. Long-term complications such as infection or erosion, loss of effect, intermittent stimulation, tolerance, and pain or discomfort can develop and need to be managed. Other factors that need consideration are social and job-related factors, development of dementia, general medical issues, and lifestyle changes. This report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society, outlines answers to a series of questions developed to address all aspects of DBS postoperative management and decision-making with a systematic overview of the literature (until mid-2004) and by the expert opinion of the authors. The report has been endorsed by the Scientific Issues Committee of the Movement Disorder Society and the American Society of Stereotactic and Functional Neurosurgery.

Bacterial Infections↗

Subthalamic nucleus deep brain stimulation: summary and meta-analysis of outcomes.

Subthalamic nucleus (STN) deep brain stimulation (DBS) is currently the most common therapeutic surgical procedure for patients with Parkinson's disease (PD) who have failed medical management. However, a recent summary of clinical evidence on the effectiveness of STN DBS is lacking. We report the results of such a systematic review and meta-analysis. A comprehensive review of the literature using Medline and Ovid databases from 1993 until 2004 was conducted. Estimates of change in absolute Unified Parkinson's Disease Rating Scale (UPDRS) scores after surgery were generated using random-effects models. Sources of heterogeneity were explored with meta-regression models, and the possibility of publication bias was evaluated. Patient demographics, reduction in medication requirements, change in dyskinesia, daily offs, quality of life, and a ratio of postoperative improvement from stimulation compared to preoperative improvement by medication from each study were tabulated and average scores were calculated. Adverse effects from each study were summarized. Thirty-seven cohorts were included in the review. Twenty-two studies with estimates of standard errors were included in the meta-analysis. The estimated decreases in absolute UPDRS II (activities of daily living) and III (motor) scores after surgery in the stimulation ON/medication off state compared to preoperative medication off state were 13.35 (95% CI: 10.85-15.85; 50%) and 27.55 (95% CI: 24.23-30.87; 52%), respectively. Average reduction in L-dopa equivalents following surgery was 55.9% (95% CI: 50%-61.8%). Average reduction in dyskinesia following surgery was 69.1% (95% CI: 62.0%-76.2%). Average reduction in daily off periods was 68.2% (95% CI: 57.6%-78.9%). Average improvement in quality of life using PDQ-39 was 34.5% +/- 15.3%. Univariable regression showed improvements in UPDRS III scores were significantly greater in studies with higher baseline UPDRS III off scores, increasing disease duration prior to surgery, earlier year of publication, and higher baseline L-dopa responsiveness. Average baseline UPDRS III off scores were significantly lower (i.e., suggesting milder disease) in later than in earlier studies. In multivariable regression, L-dopa responsiveness, higher baseline motor scores, and disease duration were independent predictors of greater change in motor score. No evidence of publication bias in the available literature was found. The most common serious adverse event related to surgery was intracranial hemorrhage in 3.9% of patients. Psychiatric sequelae were common. Synthesis of the available literature indicates that STN DBS improves motor activity and activities of daily living in advanced PD. Differences between available studies likely reflect differences in patient populations and follow-up periods. These data provide an estimate of the magnitude of the treatment effects and emphasize the need for controlled and randomized studies.

Deep Brain Stimulation↗

Methylphenidate fails to improve gait and muscle tone in patients with sporadic and hereditary spastic paraplegia.

Based on its action on multiple neurotransmitters, including dopamine, methylphenidate (MPH) is of growing interest as a possible treatment option for several movement disorders. Of special interest are diseases that share gait disturbance and cognitive decline. Based on a single case observation in a patient with hereditary spastic spinal paraplegia (HSP) in which gait was improved with MPH, we performed an open-label study with a longitudinal follow-up in 22 patients with HSP and its sporadic form (SSP). The patients were treated for 6 months with 60 mg of MPH per day. Computerized gait analysis and different scores were performed at baseline, after 6 weeks, and after 6 months of treatment. Although at 6 weeks, the gait velocity was somewhat improved, the drug failed to show any effect on other gait parameters and had no beneficial effect at all after 6 months. Although MPH is of interest for several movement disorders, our study did not show a beneficial effect.

Adenosine Triphosphatases↗

Scales in Parkinson's disease.

The search for valid instruments to measure different domains of health disturbances becomes increasingly important for the assessment of Parkinson's disease. The most widely used tool is the Unified Parkinson's Disease Rating Scale (UPDRS) which was introduced in 1987 and is currently awaiting revision. In addition, a variety of instruments have been used to capture non-motor aspects of Parkinson's disease but only a minority of these instruments has been validated for this particular disease condition. Measurements of quality of life are being incorporated into an increasing number of studies in order to reflect a more integral view of health and have contributed to a better understanding of the impact of disease and interventions. The International Classification of Functioning, Disability and Health introduced by the WHO in 2001 offers a multidimensional approach to human functioning and participation that can also be applied to the assessment of health status in PD. This workshop report will focus on the present state of clinimetry in PD and discuss future perspectives.

Disability Evaluation↗