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Biomedical subjects

R Wenzelburger

Publications and source records attributed to R Wenzelburger.

13 recordsLinked to original sources

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↗

Grip force parameters in precision grip of individuals with myelomeningocele.

The aim of this study was to characterize impairments of hand function in individuals with myelomeningocele (MMC) using a quantitative method. A grip-lift task was studied in 29 individuals with MMC (17 females, 12 males; mean age 12 years 4 months, SD 5 years 6 months; range 4 to 28 years) and 29 age- and sex-matched control participants. A small object (weight 200 g) was grasped and lifted with a precision grip of the dominant hand and grip forces (GF) and time intervals were measured. Sensibility was examined with a two-point discrimination test. In those with MMC, the latency between GF onset of the thumb and index finger and ensuing preload duration were both significantly prolonged (p<0.01). Fingertip forces were excessively high and variable. Several parameters differed significantly between those with MMC and control individuals: GF peak, GF at start of loading, mean GF, and the SDs of the GF during static holding. Although the two-point discrimination task indicated deficits of sensibility, these did not correlate with grip force parameters. Results demonstrate that fine motor skills in patients with MMC are impeded by slowness and inadequate adjustments of manipulative forces.

Adolescent↗

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↗

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↗

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.

Antiparkinson Agents↗

The gait disorder of advanced essential tremor.

Gait disturbances of patients with essential tremor (ET) have been described anecdotally, but have never been investigated quantitatively. Recent studies provided evidence for a cerebellar-like hand tremor in some patients with ET. Therefore, we designed a study to assess cerebellar-like abnormalities of leg function. Twenty-five patients with ET, eight patients with cerebellar diseases (CD) and 21 age-matched healthy subjects were studied for their normal and tandem gait using a three-dimensional gait analysis system. During normal walking, CD and ET patients showed only slight abnormalities. However, ET patients exhibited abnormalities in tandem gait with an increased number of mis-steps and a broad-based, ataxic and dysmetric gait which was indistinguishable from the findings in CD. When ET patients were separated into groups of those with or without intention tremor of the hands, the gait disorder was found to be much more pronounced in the intention tremor group. Patients with this gait disorder were more severely disturbed in their activities of daily living, and suffer from an advanced stage of ET. The present results quantitatively describe a gait disturbance in advanced ET which affects tandem gait, but leaves normal gait almost unaffected. This is strong evidence for a cerebellar-like disturbance in ET.

Adult↗

Amitriptyline enhances the central component of physiological tremor.

OBJECTIVES: Postural tremor is a regularly encountered side effect of amitriptyline which can be strong enough to cause discontinuation of therapy. The aim was to characterise amitriptyline induced tremor and to assess if the central or reflex component of physiological tremor was modulated by this drug. METHODS: The postural hand tremor was measured in 15 patients on a clinical rating scale, by power spectral analysis of accelerometer, forearm flexor, and extensor EMG before and after the beginning of amitriptyline treatment for major depression or chronic pain syndrome. A coherence analysis between flexor and extensor muscles on the same side was performed. RESULTS: There was a clinically visible increase in postural tremor in a third of these patients. The tremor amplitude measured by accelerometer total power increased in every patient under amitriptyline. The EMG synchronisation as reflected by significant peaks in the flexor or extensor spectrum generally occurring at higher frequencies (8-18 Hz) than the accelerometric tremor frequencies (6-11 Hz) did not change. The number of patients with a significant flexor-extensor coherence in the 7-15 Hz range increased significantly under amitriptyline, the frequency bands of significant coherence corresponded with the EMG frequencies, and both were independent of changes to the hand's resonant frequency by added inertia. CONCLUSIONS: An enhancement of postural tremor under amitriptyline is a common phenomenon although not always clinically apparent. The increase in EMG-EMG coherence indicates an increased common central drive to the motor units as its frequency is not influenced by peripheral resonance or reflex mechanisms. This is the first account of a drug induced enhancement of the central component of physiological tremor.

Amitriptyline↗

Multiple oscillators are causing parkinsonian and essential tremor.

The tremors of Parkinson's 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 (delta 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 involved-spinal pathways.

Arm↗

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 Parkinson's 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.

Adult↗

Determinants of physiologic tremor in a large normal population.

OBJECTIVES: It has been well established that peripheral mechanical resonant factors as well as central mechanisms may play a role in the generation of physiological tremor (PT). Furthermore it has been postulated that subject's attributes like age and sex might influence PT. The present study was designed to quantify these influences on PT in a large normal population. METHODS: Physiological hand and finger tremors were measured in a group of 117 normal subjects between 20 and 94 years of age using accelerometry and surface EMG recordings from the forearm flexor and extensor muscles. The hand tremor was measured in a postural position with and without weight, and the finger tremor was recorded with the arm outstretched, forearm supported and hand supported. Hand volume and grip force were measured in each subject. RESULTS: Hand tremor frequency (mean 7.7 Hz) was reduced significantly by added inertia (mean 5.2 Hz) and it was negatively correlated with hand volume while there was no correlation with grip force. Finger tremor showed, subject to the arm position, maximally 3 and at least two distinct frequency bands (1-4, 6-11 and 15-30 Hz) reflecting the resonance frequencies of the whole arm, the hand and the finger, respectively. A significant EMG peak was found in 50-80% of the recordings. This EMG synchronization gave rise to a corresponding accelerometer peak or a significant EMG-EMG coherence in about one-third of the population indicating a central component of PT because its frequency was unaffected by mechanical changes in the periphery. We did not find a significant influence of age on the tremor frequency, while the sex of the subjects slightly but significantly changed the frequency range of hand tremor. Multiple partial correlations revealed, however, that the only direct influence on hand tremor frequency is the hand volume indicating that the influence of sex on hand tremor frequency is an indirect effect produced by the significantly larger hands of male subjects. CONCLUSIONS: In conclusion, the main determinants of PT are the mechanical properties of the oscillating limb. Apart from the dominating peripheral resonance mechanism we found indications of an additional central component of PT in about one-third of the normal population. There was no age dependence of tremor frequency and it was shown that the influence of the subjects' sex on tremor frequency only represents an indirect mechanical effect.

Adult↗

Essential tremor and cerebellar dysfunction clinical and kinematic analysis of intention tremor.

The cerebellum is assumed to play a major role in the pathophysiology of essential tremor (ET). As intention tremor is considered one of the classical features of cerebellar disease, we have assessed a large group of patients with ET for the semiology of the tremor and have performed objective quantitative analysis of a grasping movement in patients with ET, cerebellar disease and a normal control group. We found 25% of the patients to have a moderate or severe kinetic tremor with clear-cut features of a classical intention tremor. Another 33% of the patients had a mild intentional component of their kinetic tremor. Patients with intention tremor (ET(IT)) did not differ from those with predominant postural tremor (ET(PT)) with respect to alcohol sensitivity of the tremor and the frequency of a family history. ET(IT) patients were older and more often showed head and trunk involvement. The onset of this intention tremor has been assessed retrospectively. It was found to begin at a randomly distributed time interval after the onset of the postural tremor, but older patients had a shorter time to development of intention tremor. Quantitative accelerometry of postural tremor showed similar tremor frequencies in both patient groups, but ET(IT) patients had a slightly larger tremor amplitude. Quantitative analysis of a grasping movement using an infrared-camera system was performed in two subgroups of the patients with ET(PT) and ET(IT) and control groups with cerebellar disease or normal subjects. The intention tremor could be quantified objectively as an increased amplitude of curvature during the deceleration and target phase of the movement. The amplitude measurements of intention tremor were clearly abnormal and of comparable magnitude for ET(PT) and cerebellar disease. Additionally, the patients with ET(IT) had a significantly slowed grasping movement during the deceleration and target period. Hypermetria was significantly increased for the patients with ET(IT) and cerebellar disease. We conclude that intention tremor is a feature of ET. ET(IT) patients have abnormalities of their upper limb function compatible with cerebellar disease. This suggests that patients with more advanced ET show abnormalities of cerebellar functions.

Adolescent↗

Tremor.

Tremor research during the past year has focused on clinical differential diagnosis, and a new clinical classification has been developed. The origin of tremor is thought to depend on unstable central loops, and new coherence data suggest that these often involve the motor cortex. Gabapentine has been assessed for efficacy in some tremors, and deep brain stimulation of the ventrolateral thalamus has been shown to be safer and more effective for severe essential and parkinsonian tremor than thalamotomy.

Diagnosis, Differential↗