Biomedical subjects

J Raethjen

Publications and source records attributed to J Raethjen.

13 recordsLinked to original sources

PubMed2001

Delay estimation for cortico-peripheral relations.

In neurophysiology, time delays between concurrently measured time series are usually estimated from the slope of a straight line fitted to the phase spectrum. We point out that this estimate is valid only in the case in which, one signal is a mere time-delayed copy of the other one. We present a procedure for delay estimation that applies to a much wider class of systems with nontrivial phase spectrum like for example lowpass filters. The procedure is based on the Hilbert transform relation between the phase of a linear system and its log gain. The Hilbert transform relation is nonlocal in frequency space, a fact that limits its applicability to experimental data. We explore these limits, and demonstrate that the method is applicable to neurophysiological time series. We present the successful application of the Hilbert transform behavior method to concurrently recorded epicortical brain activity and peripheral tremor. We point out and explain physiologically unreasonable delay estimates given by the traditional method. Finally, we discuss the assumptions underlying the applicability of the Hilbert transform method in the neuroscience context.

Cerebral Cortex↗

PubMed2001

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↗

PubMed2001

The pathophysiology of tremor.

Tremor is defined as rhythmic oscillatory activity of body parts. Four physiological basic mechanisms for such oscillatory activity have been described: mechanical oscillations; oscillations based on reflexes; oscillations due to central neuronal pacemakers; and oscillations because of disturbed feedforward or feedback loops. New methodological approaches with animal models, positron emission tomography, and mathematical analysis of electromyographic and electroencephalographic signals have provided new insights into the mechanisms underlying specific forms of tremor. Physiological tremor is due to mechanical and central components. Psychogenic tremor is considered to depend on a clonus mechanism and is thus believed to be mediated by reflex mechanisms. Symptomatic palatal tremor is most likely due to rhythmic activity of the inferior olive, and there is much evidence that essential tremor is also generated within the olivocerebellar circuits. Orthostatic tremor is likely to originate in hitherto unidentified brainstem nuclei. Rest tremor of Parkinson's disease is probably generated in the basal ganglia loop, and dystonic tremor may also originate within the basal ganglia. Cerebellar tremor is at least in part caused by a disturbance of the cerebellar feedforward control of voluntary movements, and Holmes' tremor is due to the combination of the mechanisms producing parkinsonian and cerebellar tremor. Neuropathic tremor is believed to be caused by abnormally functioning reflex pathways and a wide variety of causes underlies toxic and drug-induced tremors. The understanding of the pathophysiology of tremor has made significant progress but many hypotheses are not yet based on sufficient data. Modern neurology needs to develop and test such hypotheses, because this is the only way to develop rational medical and surgical therapies.

Animals↗

PubMed2001

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↗

PubMed2001

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

The pathophysiology of parkinsonian tremor: a review.

Parkinsonian tremor is most likely due to oscillating neuronal activity within the CNS. Summarizing all the available evidence, peripheral factors only play a minor role in the generation, maintenance and modulation of PD tremor. Recent studies have shown that not a single but multiple oscillators are responsible. The most likely candidate producing these oscillations is the basal ganglia loop and its topographic organization might be responsible for the separation into different oscillators which, nevertheless, usually produce the same frequency. The neuronal mechanisms underlying these oscillations are not yet clear, but three hypotheses would be compatible with the presently available data from animal models and data recorded in patients. The first is a cortico-subthalamo-pallido-thalamic loop, the second is a pacemaker consisting of the external pallidum and the subthalamic nucleus, and the third is abnormal synchronization due to unknown mechanisms within the whole striato-pallido-thalamic pathway leading to a loss of segregation. Assuming the oscillator within the basal ganglia pathway, the mechanism of stereotactic surgery might be a desynchronization of the activity of the basal ganglia-thalamo-cortical or the cerebello-thalamo-cortical pathway.

Animals↗

PubMed2000

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↗

PubMed2000

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↗

PubMed2000

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↗

PubMed1998

Shaping of the cat paw for food taking and object manipulation: an X-ray analysis.

The kinematics of the cat distal forelimb during food-taking were analysed to obtain information on the movement processes within the paw before and during object taking in a species without monosynaptic corticomotoneuronal projections. The behaviour was investigated with two tests: either the table test (TT, food offered on a table located at ground level in a reaching distance of 22 and 28 cm) or the horizontal test (HT, food offered in a small container located at shoulder level, height 18-25 cm, reaching distance 6-12 cm). In five animals, the changes in configuration and the conjoint actions of the wrist, the metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints were assessed with three-dimensional X-ray cinematography (time resolution 20 ms, spatial resolution 1 mm) and video analysis. While approaching the target, the digits were first extended and subsequently abducted. This 'preshaping' consisted of combined angular changes in the MCP and PIP joints, thereby attaining an adequate grip aperture. Each cat used a stable strategy, but different cats used different strategies. In the TT, preshaping involved an MCP extension and a PIP flexion. In the HT, predominant extension of the MCP, predominant extension of the PIP, or a combination of both were used, followed by MCP flexion and PIP flexion. The grip aperture started to decrease before object contact, earlier in the TT, later in the HT. Grasping was achieved by flexion of first the PIP and later the MCP. The X-ray analysis gave evidence for individuated digit movements. Correlation analysis of the angular position of the joints between the different phalanges showed that digits 3 and 4 acted in concert, as did digits 2 and 5, but with clear independence between the different pairs. Furthermore, the different phalanges served different purposes during the grasp. Digits 3, 4 established object contact, digits 2, 5 were mainly used to stabilize the paw onto the surface. The cat distal forelimb displays a refined movement repertoire during the preshaping and grasping phase of food-taking. During the preshaping phase, the kinematics resembled in some aspects the situation in humans. The results demonstrate the ability of the polysynaptic projections from the cortico-motoneuronal system to organize differentiated distal limb movements, including individuated movements of the digits.

Animals↗

PubMed1997

Selective autonomic and sensory deficits in slow transit constipation.

Chronic idiopathic constipation is likely to be a heterogeneous condition. Our previous studies on the stimulated sweating response suggested that autonomic dysfunction may be a cause in a subset of patients. Our aims were to test selectively the neural and sweat gland components of the sweat response and to test unmyelinated sensory fibres so as to determine whether a small fibre neuropathy is present. Twelve female patients with proven slow transit constipation and nineteen age-matched healthy volunteers took part in the study. The sensory tests included thermal thresholds and axon reflex vasodilatation in response to intradermal capsaicin, measured with a laser Doppler. Direct and axon reflex sweating was induced with intradermal methacholine and nicotine, respectively, and measured with an evaporimeter. Non-parametric tests were used for statistical comparison with a group of seven control subjects. Results are expressed as medians and range. All four patients who reported constipation from childhood had a selective deficit of unmyelinated afferent fibre function in the feet, with markedly elevated thresholds to warm sensation (controls 5.2; 4.3-10.6, patients 13.8; 11.8-16.1 delta T (degree C), P < 0.02) and heat pain (controls 10.6; 8.2-14.7, patients 18.1; 13.9-22.6 delta T (degree C), P < 0.05) and a reduced response to capsaicin (controls 47.0; 24-117, patients 13.5; 12-30 delta Flux (V), P < 0.005). In contrast, patients with adult onset constipation (n = 7) had a selective neural sweating deficit (controls 49.8; 32.0-61.8; patients 27.7; 7.3-44.3 g/m2 h, P < 0.05), indicating dysfunction of post-ganglionic sympathetic cholinergic fibres. Patients from both groups were shown to have normally functioning sweat glands in direct response to methacholine. Our findings suggest that patients with severe chronic idiopathic constipation may have selective small fibre neuropathies, of which constipation is a manifestation.

Adult↗