The NMDA antagonist budipine can alleviate levodopa-induced motor fluctuations.
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Adult↗
Biomedical subjects
S Spieker
Publications and source records attributed to S Spieker.
Tremorlytic activity of budipine in Parkinson's disease.
In order to objectively quantify the tremorlytic activity of budipine in Parkinson's disease (PD) we performed longterm tremor recordings in a subset of patients enrolled in two clinical trials. Eleven PD patients with marked tremor participating in an open-label study underwent longterm recording before and during medication. Nine patients completed the study. Tremor occurrence was reduced from 52 +/- 18.6% to 34.7 +/- 19.3% (p < 0.05); tremor intensity decreased from 15.3 +/- 4.8 (SNR) to 11.3 +/- 4.8 (p < 0.01). UPDRS tremor subscores were also significantly improved. Fourteen patients who enrolled in a multicenter, double-blind, placebo-controlled study underwent longterm tremor analysis in addition to the Columbia University Rating Scale (CURS). Tremor occurrence was improved in the budipine group (n = 7) from 24.7 +/- 15.5% to 14.8 +/- 14.5% (p < 0.05). Tremor intensity decreased from 9.1 +/- 2.5 (SNR) to 7.2 +/- 1.6. However, the latter result was statistically not significant, probably due to the small patient number. In the placebo-group (n = 7) there was no reduction of tremor occurrence or of tremor intensity. The CURS sum score was improved from 5.7 to 3.0 in the budipine group, whereas there was only a smaller improvement in the placebo group (from 7.1 to 5.5). These data suggest that budipine is an effective tremorlytic agent in PD, which may be used as an alternative to anticholinergics.
Aged↗
Long-term measurement of tremor.
To account for the fluctuating and context-dependent nature of tremor, the method of ambulatory long-term electromyography (EMG) was developed for quantification of this symptom. It is based on successive evaluation of 15-s intervals by using a fast Fourier transformation (FFT). The standard results obtained are (a) tremor occurrence, a measure of how many intervals contain tremor; (b) mean tremor intensity; and (v) mean tremor frequency. This new method fulfills the so-called "test criteria" such as reliability, validity, sensitivity, and specificity for tremor quantification in essential tremor (ET) and Parkinson's disease (PD). In addition, we developed a method of determining the antagonist activation pattern by using cross-correlation analysis, also based on the long-term approach. This allows differentiation between ET and PD with a high sensitivity and a high interrater reliability. We conclude that long-term EMG is useful for both quantification and differentiation of tremor.
Diagnosis, Differential↗
Acute disseminated encephalomyelitis following Pontiac fever.
We report the case of a 35-year-old woman who developed headache and psychosis and gradually became comatose within 3 weeks after a flu-like infection. MRI revealed bifrontal demyelination consistent with acute disseminating encephalomyelitis (ADEM). Two different cerebrospinal fluid samples were positively tested for Legionella cincinnatiensis by direct sequencing of a PCR-amplified Legionella-specific fragment. This result made it possible to interpret the initial symptoms as Pontiac fever. We think it most likely that this is a case of ADEM following the very rare situation of a systemic infection with L. cincinnatiensis. A review of the literature on Legionella-associated encephalopathy suggests that some of these cases may also have had ADEM.
Adult↗
Control of repetitive lip and finger movements in Parkinson's disease: influence of external timing signals and simultaneous execution on motor performance.
This study addresses the question of whether external timing signals and/or simultaneous rhythmic movements of other limbs can alleviate sequencing motor deficits associated with Parkinson's disease (PD). Subjects performed rhythmic lip and finger movements simultaneously or in isolation. In addition, they had to self-pace their movements or match them to an external signal. Our results are summarized as follows: (1) Seven of 12 patients had adequate mean repetition rates; that is, they fulfilled the task requirements on a global scale. The remaining five patients had various degrees of hastened responses and were not fully able to synchronize their movements to an external pacing signal. (b) PD patients exhibited hypometria in their finger tapping, but not in their lip movements. Their movements were not abnormally slowed, but peak velocity was appropriately scaled, even to reduced movement amplitudes. (c) Mean repetition rates, stability of frequency response, and kinematics did not differ between conditions of external and internal stimulation within the PD group, but were different form the control group performance. (d) Kinematic measures were not improved during dual-task execution. PD patients were not able to maintain a 1:1 rhythm between effectors. The incidence of hastening increased during simultaneous motor execution. We conclude that the use of external pacing signals might aid movement initiation of PD patients, but does not improve their temporal or spatial coordination when generating repetitive movements. Simultaneous execution does not necessarily enhance motor performance, but might actually have detrimental effects in patients prone to hastening.
Aged↗
Validity of long-term electromyography in the quantification of tremor.
We previously developed a method of tremor quantification using long-term electromyography registration of antagonistic forearm muscles that is reliable, sensitive, and specific for pathologic tremors. The present study demonstrates that tremor occurrence as measured by this method correlates well with clinical parameters of tremor in idiopathic Parkinson's disease (PD) and essential tremor (ET) (subscores of the Unified Parkinson's Disease Rating Scale for PD, tremor rating according to Bain et al. for ET). We conclude that the method is a valid and objective means of tremor quantification in PD and ET.
Activities of Daily Living↗
Kinematic analysis of articulatory movements in central motor disorders.
The various components of the central motor system are expected to play a similar role in speech production and in upper limb control. Slowed articulatory performance, therefore, must be expected in disorders of the corticobulbar tracts, cerebellum, and basal ganglia. Using an optoelectronic device, the present study recorded lower lip trajectories during production of sentence utterances in patients with Parkinson's disease (PD), Huntington's disease (HD), cerebellar atrophy (CA), and pseudobulbar palsy (PB). The various subject groups showed a similar range of overall motor disability. Patients with CA and PB exhibited slowed movement execution in terms of a reduced ratio of peak velocity to maximum amplitude ("stiffness"). In contrast to upper limb motor control, the lip excursions showed an uncompromised shape of velocity profiles. Two different patterns emerged in HD. A single patient suffering from the akinetic-rigid Westphal variant of this disease had articulatory hypometria, whereas the remaining subjects showed significant bradykinesia under increased temporal demands, concomitant with normal movement amplitudes. The PD patients had unimpaired velocity-displacement relationships. Presumably, biomechanical constraints such as the rather small excursions of articulatory lower lip gestures or the scarce spindle supply of facial muscles account for the observed discrepancies between upper limb and speech motor control in PD.
Aged↗
Infants of depressed and nondepressed mothers exhibit differences in frontal brain electrical activity during the expression of negative emotions.
Studies have shown that infants of depressed mothers express negative emotions more frequently than infants of nondepressed mothers. The present study examined electrical brain activity during expression of negative and positive emotions in infants of depressed and nondepressed mothers. Infants, 11 to 17 months of age, were exposed to conditions designed to elicit positive and negative emotions while electroencephalographic (EEG) activity was measured from left and right, frontal and parietal regions. EEG activity was analyzed when infants were displaying prototypic expressions of emotions. Compared with infants of nondepressed mothers, infants of depressed mothers exhibited increased EEG activation in the frontal but not parietal region when expressing negative emotions (unfelt smiles and anger). The two groups of infants did not show reliable differences is brain activation during the expression of positive emotions (happiness, surprise) or neutral expressions. Compared with infants of nondepressed mothers, infants of depressed mothers exhibit greater frontal EEG activation during the expression of negative emotions.
Anger↗
Fractal dimension of sustained vowel productions in neurological dysphonias: an acoustic and electroglottographic analysis.
In order to investigate whether nonlinear methods of signal analysis provide a measure of phonatory irregularities in neurogenic voice disorders, the present study computed the fractal dimension (D) both of the electroglottographic (EGG) and the acoustic signal of sustained vowel productions obtained from patients with Parkinson's disease (PD) and cerebellar atrophy (CA). Compared with normal speakers, the female PD group as well as the male and female CA patients showed an increased dimension (D) of the EGG. The dimensional complexity of the acoustic signal largely depended on vowel type. Furthermore, the dimension of the acoustic signal was reduced in male PD patients as compared to the respective controls.
Brain↗
Classical eyeblink conditioning in Parkinson's disease.
Patients with Parkinson's disease (PD) show impairments of a range of motor learning tasks, including tracking or serial reaction time task learning. Our study investigated whether such deficits would also be seen on a simple type of motor learning, classic conditioning of the eyeblink response. Medicated and unmediated patients with PD showed intact unconditioned eyeblink responses and significant learning across acquisition; the learning rates did not differ from those of healthy control subjects. The overall frequency of conditioned responses was significantly higher in the medicated patients with PD relative to control subjects, and there was also some evidence of facilitation in the unmedicated patients with PD. Conditioning of electrodermal and electrocortical responses was comparable in all groups. The findings are discussed in terms of enhanced excitability of brainstem pathways in PD and of the involvement of different neuronal circuits in different types of motor learning.
Adult↗
Wrist tremor: investigation of agonist-antagonist interaction by means of long-term EMG recording and cross-spectral analysis.
We have developed a method to observe and quantify the phasic relationship between the burst patterns of antagonistic muscles in any roughly periodic movement, such as tremor, for up to 24 h. This paper describes our approach, in which long-term EMG recordings are evaluated by a procedure based on cross-spectral analysis. The method is then illustrated by data from 6 patients with essential tremor. Our data confirm earlier observations that a particular patient may show different burst patterns at different times. However, as opposed to tremor analysis based on short-term recording, our method allows quantitative statements on the relative frequency of the burst patterns, as they occur under everyday conditions. In addition, our data suggest that in ET (a) alternating tremor activity in one hand may occur simultaneously with synchronous activity in the other hand; (b) along with the classical alternating and co-contracting patterns there may be significant 'non-classical' activity, that cannot be called alternating or synchronous.
Aged↗
A defect of kinesthesia in Parkinson's disease.
Patients suffering from Parkinson's disease (PD) are more dependent on visual feedback during movement than are normals. Studying two-dimensional pointing movements, we recently found that PD patients undershoot targets when vision of their own moving hand is occluded but not when complete vision is provided or when the target is extinguished immediately before movement onset. In the absence of vision, information about position of the moving hand may originate from peripheral kinesthetic feedback and from corollary discharges derived from the efferent motor signal. To find out which of both mechanisms--kinesthetic feedback or corollary discharge--is defective in PD, we compared active movements with imposed movements in which the hand is passively moved by the experimenter, whereas vision of the hand was occluded under either condition. In agreement with our earlier findings, slow, active pointing movements of PD patients were hypometric. In addition, PD patients terminated passively imposed movements of comparable speed earlier than did normals, with the consequence that imposed movements were equally hypometric. Our results make it unlikely that disturbed corollary discharge is responsible for hypometria under nonvisual conditions. Instead, the data suggest that PD patients have a defect of kinesthesia in slowly executed movements.
Adult↗
Zotepine in levodopa-induced Psychosis.
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Aged↗
Fixation instability and oculomotor abnormalities in Friedreich's ataxia.
Eye movements were studied in 13 patients with Friedreich's ataxia and correlated with MRI findings to investigate whether oculomotor abnormalities can be traced to cerebellar disturbances in this disease. One of the most prominent eye signs was fixation instability (square-wave jerks, SWJ.). Besides SWJ the patients showed various combinations of cerebellar, vestibular and brain-stem oculomotor signs. Our patients did not comprise a homogeneous group with regard to their oculomotor findings. There was no correlation between the severity of any of the so-called cerebellar oculomotor disturbances and the number of SWJ. We tried to correlate the extent of oculomotor disturbances with floccular atrophy and atrophy of the dorsal vermis on MRI in seven of the patients. None of the oculomotor features (including SWJ) correlated with flocculus or dorsal vermis size. Furthermore, floccular and vermal measurements on MRI were normal. Accordingly, we think it unlikely that the oculomotor disturbances, including SWJ, are attributable to cerebellar pathology per se.
Adult↗
Reliability, specificity and sensitivity of long-term tremor recordings.
We have developed a method of long-term EMG recording that has proven suitable for the quantification of pathological tremor. In the present paper we show that the principal parameters of the method (tremor occurrence, tremor intensity, tremor frequency) are highly reproducible and that the method is specific and sensitive for detection of pathological tremor. Twelve patients with essential tremor (ET) and 13 patients with Parkinson's disease (PD) were recorded repeatedly on 3 successive days. For each patient group and for each parameter the intersubject variability was much larger than the intersubject variability. The intraclass correlation coefficient "R" was in the order of 0.9 for each parameter and the mean of Pearson's correlation coefficient between successive days was also approximately 0.9. Recordings from normal controls demonstrated that the method's specificity for pathological tremor is 94.1% and its sensitivity is 96%.
Adult↗
Memory and skill acquisition in Parkinson's disease and frontal lobe dysfunction.
Animal experiments and human neuropsychological studies have provided evidence for the hypothesis that skill acquisition may be regulated by the basal ganglia. In the present studies, perceptual and cognitive skill acquisition as well as a number of explicit verbal memory functions were investigated in patients in early and more advanced stages of Parkinson's disease (PD) and in patients with frontal lobe lesions. Patients in more advanced stages of PD were impaired at cognitive skill acquisition as well as during recall conditions that involved active semantic organisation of the stimulus material. Similar explicit memory deficits were present in frontally lesioned patients. PD patients with unilateral symptoms showed a selective impairment in acquiring a cognitive skill. Perceptual skill acquisition was preserved in all groups. The overall pattern of memory impairment in PD is largely consistent with dysfunction of fronto-striatal circuitry.
Corpus Striatum↗
Tremorlytic activity of budipine: a quantitative study with long-term tremor recordings.
The tremorlytic activity of the novel antiparkinson agent budipine was quantified in an open trial. Eleven patients with Parkinson's disease (PD) were treated with individual doses of budipine added to stable conventional antiparkinsonian medication. Tremor activity was measured using long-term electromyogram (EMG) recordings. Tremor intensity was reduced by 25%, tremor occurrence by 34%, and conventional "Unified Parkinson's Disease Rating Scale" (UPDRS) scores improved by 20% with this medication. There were two dropouts because of side effects. One dropout appeared not to be related to budipine. Apart from those, the drug was well tolerated by all patients. We conclude that budipine is an effective and well-tolerated tremorlytic drug and that the method of long-term EMG recording is suitable for tremor quantification in clinical studies.
Adult↗
Long-term tremor recordings in parkinsonian and essential tremor.
We have recently developed a method of long-term EMG recording (Bacher et al., 1989), which has proven suitable for the quantification of pathological tremor. In the present paper we show that (1) the principal parameters of the method (tremor occurrence, tremor intensity, tremor frequency) are highly reproducible with intraclass correlation coefficients in the order of 0.9, (2) that the method has both a high specificity (87.5%) and sensitivity (96%) for detection of pathological tremor, and (3) that it can be useful for examining agonist-antagonist muscle activation under everyday conditions.
Adult↗