Roland Wenzelburger

Multiple oscillators are causing parkinsonian and essential tremor

The tremors of Parkinsons disease (PD) and essential tremor (ET) are traditionally considered to depend on a central oscillator producing rhythmic activation of the motoneurones of all extremities. To test this hypothesis, we have compared electromyographic tremor activity in different muscles of the affected limbs using cross spectral analysis, including coherence and phase. Surface electromyographic recordings from both arms, legs, and the neck were analyzed in 22 patients with PD and 28 patients with ET. Volume conduction between neighboring muscles producing artificial “coherence” has been found to be an important methodologic problem. We have developed a mathematical test to exclude data that could distort the results. According to this test, 10% or 25% of muscle combinations from the same limb had to be excluded from further analysis in PD or ET, respectively. In both, patients with PD and ET, we found a considerable number of muscle combinations oscillating at virtually the same frequency (▵ frequency <0.4 Hz) without showing a significant coherence. Thus, the frequency difference between different muscles is not sufficient to measure the correlation between two muscles. Significant coherencies between muscles within the same arm or leg were found in 70% or 90% of patients with PD or ET, respectively, whereas only one patient with PD and not a single patient with ET showed significant coherencies between muscles from different limbs. The phase between coherent muscles of the same arm of patients with PD showed a preference of either a reciprocal alternating pattern for antagonistic muscles in forearm flexor and upper arm extensor as opposed to a co‐contraction pattern between the hand flexors and the triceps brachii. In patients with ET such clear differences were lacking. We conclude that multiple oscillators are responsible for the tremor in different extremities of patients with PD and ET. Differences between PD and ET concerning the phase relation within the arm may either be related to the topography within the basal ganglia or to differently involvedspinal pathways.

Effects of bilateral subthalamic nucleus stimulation on parkinsonian gait

Gait analysis was carried out to assess the effects of l-dopa and bilateral subthalamic nucleus stimulation on gait velocity, cadence, stride length, and gait kinematics in nine patients with PD. Substantial effects of bilateral subthalamic nucleus stimulation on gait, with an increase in gait velocity and stride length comparable to that of a suprathreshold l-dopa dose, were found. Interestingly, stride length was more improved by l-dopa and cadence more by subthalamic nucleus stimulation. In two patients with freezing during the “on” period, subthalamic nucleus stimulation failed to reduce this symptom effectively.

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.

Influence of alcohol on gait in patients with essential tremor

Objective: To study the effect of ethanol on gait in patients with essential tremor (ET). Methods: Using a three-dimensional opto-electronic gait analysis system, the authors analyzed gait at free-speed walking, at a given velocity, and during tandem gait. Patients with ET with advanced disease were examined before and after a small oral dose of ethanol. The results of the patients with ET were compared with those from age-matched healthy controls (HCs). The primary outcome criteria were the number of missteps and the ataxia score during tandem gait. Results: Before alcohol, patients with ET had more missteps and an abnormal ataxia score compared with HCs. The ingestion of alcohol with a mean blood level of 0.45% led to a significant improvement of the ataxia score and the number of missteps. HCs showed a worsening of the ataxia score and an increase of the number of missteps after alcohol, which failed to reach significance. Conclusions: Orally administered ethanol improved gait ataxia in patients with essential tremor (ET). This may reflect a reversible effect of ethanol on receptors being involved in the pathology of ET. Ethanol may act via an influence of the inferior olive or directly on alcohol-sensitive γ-aminobutyric acid receptors within the cerebellum.

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

Abstract. 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.

Subthalamic nucleus stimulation for Parkinson's disease preferentially improves akinesia of proximal arm movements compared to finger movements

Deep brain stimulation of the subthalamic nucleus (STN‐DBS) reduces akinesia in Parkinsons disease but its impact on fine motor functions was unknown. We assessed the effects of DBS and a levodopa (L‐dopa) test on the timing of the precision grip in 18 patients. Improvement on UPDRS‐items reflecting hand functions and the shortening of the first phases of the precision grip were more distinct in the L‐dopa test than in the pure STN‐DBS condition. Other akinesia items and the time for build‐up of lifting force were equally improved in both conditions. This suggests that routine STN‐DBS might not be equally effective on all aspects of fine motor functions.

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.

Dyskinesias and grip control in Parkinson's disease are normalized by chronic stimulation of the subthalamic nucleus.

Deep‐brain stimulation of the subthalamic nucleus appears to reduce levodopa‐induced dyskinesias, but whether this effect is caused by the reduction of the total levodopa ingestion or represents a direct effect on the motor system is unknown. Precision grip force of grasping movements and levodopa‐induced dyskinesias was analyzed in 10 parkinsonian patients before and after 3 months of deep‐brain stimulation of the subthalamic nucleus. Peak grip force was abnormally increased before surgery in the off‐drug state and, particularly, in the on‐drug state (sensitization). This grip force upregulation normalized with chronic deep‐brain stimulation in both conditions (desensitization). Peak‐dose dyskinesias also improved, and off‐dystonia was completely abolished. Mean dosage of dopaminergic drugs was reduced, but force overflow and dyskinesias were equally improved in 2 patients without a reduction. Despite the same single levodopa test dose, force excess and levodopa‐induced dyskinesias were drastically reduced after 3 months of deep‐brain stimulation of the subthalamic nucleus. This indicates that direct effects of deep‐brain stimulation of the subthalamic nucleus on levodopa‐induced dyskinesias are likely to occur. Grip force overflow is a promising parameter to study the desensitizing effect of chronic deep‐brain stimulation on levodopa‐induced dyskinesias.

Kinetic tremor in a reach-to-grasp movement in Parkinson's disease

The aim of this study was to quantify the tremor of the hand during a natural movement (kinetic tremor) in tremor‐dominant parkinsonian patients (n = 13). We used a three‐dimensional camera system to kinematically analyze rest and kinetic tremors in an unrestrained reach‐to‐grasp movement, and additional tremor recordings were performed under standard postural and rest conditions using electromyography and accelerometry. The standard analysis showed a highly synchronized tremor with similar frequencies at rest and in sustained postural tasks, with and without loading. A kinematic recording was used to compare rest and action conditions. A strong inhibition of the resting tremor was present at the onset of the movement and reached its peak during deceleration. A kinetic tremor of low amplitude was present in most of the parkinsonian patients, but its occurrence was confined mainly to the terminal periods of the movement. The frequency of kinetic tremor was significantly higher than that at rest, before the onset of the movement in Parkinsons disease, as determined by the kinematic analysis (mean, 5.5 Hz vs 6.5 Hz; p <0.01). Our results confirm similarities between the tremor at rest and the oscillations during a sustained postural task in classic parkinsonian tremor. In contrast to this stable tremor, which seems to be generated by basal ganglia oscillators, a different pathophysiology of oscillations during motion must be considered. The kinetic tremor is most likely related to an enhancement of the physiologic tremor in the terminal phase of the reach‐to‐grasp movement.

Gait analysis of sporadic and hereditary spastic paraplegia

Abstract.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.