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Biomedical subjects

S Spieker

Publications and source records attributed to S Spieker.

At least 19 recordsLinked to original sources

Development and evaluation of the Parkinson Psychosis Questionnaire A screening-instrument for the early diagnosis of drug-induced psychosis in Parkinson's disease.

OBJECTIVE: Drug-induced psychosis is a frequent side-effect in the treatment of advanced Parkinson's disease (PD). We sought to develop and evaluate a brief instrument for early recognition of drug-induced psychosis in PD. METHODS: We developed the "Parkinson Psychosis Questionnaire" (PPQ), which consists of screening questions for typical early signs and psychotic symptoms in PD and which quantifies the frequency and severity of four clinical categories-sleep disturbances, hallucinations/illusions, delusions and orientation. We performed an internal validation of the PPQ in 50 unselected patients with parkinsonism. The Brief Psychiatric Rating Scale (BPRS) and the "Structurized Clinical Interview" (SCID) for DSM IV were applied to the same patients as external references. RESULTS: Of 50 subjects, 49 suffered from idiopathic PD and one from probable MSA-P. Hoehn and Yahr stages in "on" ranged from 1.5 to 4. Sensitivity of the PPQ test for drug-induced psychosis according to SCID was 100 % (95 % CI: 73.5%, 100%); while specificity was 92.1 % (95% CI: 78.6%, 98.3 %). The PPQ severity score was highly correlated with BPRS. We derived a linear prediction formula, which transformed PPQ into BPRS scores. CONCLUSION: The PPQ appears to be a suitable, and easily administered instrument for early diagnosis of drug induced psychosis in routine PD care. Whether the PPQ could also be a valuable tool for monitoring follow-up studies and therapeutic intervention trials remains to be tested.

Antiparkinson Agents↗

Catechol-O-methyltransferase inhibitors versus active comparators for levodopa-induced complications in Parkinson's disease.

BACKGROUND: As Parkinson's disease progresses the control of the symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of the levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase. OBJECTIVES: To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus active comparators in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of the Cochrane Controlled Trials Register (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted. SELECTION CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor therapy versus an active comparator in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data was abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: Two trials were found that examined the efficacy of a COMT inhibitor against an active comparator (n = 349). Koller 1998 compared the efficacy of tolcapone versus pergolide (n = 203) over 12 weeks and TSG 1999 compared the efficacy of tolcapone versus bromocriptine (n = 146) over 8 weeks. No trials were found that compared entacapone with active comparators. Tolcapone produced similar benefits to bromocriptine in 'off' time reduction, motor impairment and disability ratings over three months of therapy. Tolcapone produced a greater reduction in levodopa dosage than bromocriptine. Tolcapone produced similar benefits to pergolide in levodopa dose reduction, motor impairment and disability ratings, and in generic health-related quality of life scales over the first two months of therapy. Tolcapone produced a greater improvement in the disease-specific quality of life scale PDQ-39 than pergolide. Nausea, constipation and orthostatic complaints were greater with agonist therapy, but otherwise the frequency of adverse events and withdrawals from treatment were similar with the two classes of adjuvant medication. One patient had significantly elevated liver enzymes whilst on tolcapone, but otherwise the frequency of adverse events and withdrawals from treatment were similar. REVIEWERS' CONCLUSIONS: The two trials comparing tolcapone with the dopamine agonists bromocriptine and pergolide were underpowered to detect clinically relevant differences between them. This is based on medium-term evidence. No evidence was found comparing entacapone with active comparators. Further larger and longer-term trials are required to compare tolcapone with entacapone and COMT inhibitor therapy with alternative adjuvant classes of drug in later Parkinson's disease such as dopamine agonists and monoamine oxidase inhibitors.

Antiparkinson Agents↗

Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease.

BACKGROUND: As Parkinson's disease progresses the control of motor symptoms often requires the addition of other drugs to levodopa. The principle aim of COMT inhibitor therapy is to increase the duration of effect of each levodopa dose and thus reduce the time patients spend in the relatively immobile 'off' phase. OBJECTIVES: To compare the efficacy and safety of adjuvant COMT inhibitor therapy versus placebo in patients with Parkinson's disease, already established on levodopa and suffering from motor complications. SEARCH STRATEGY: Electronic searches of the Cochrane Controlled Trials Register, (The Cochrane Library Issue 1, 2003), MEDLINE (1966-2003), EMBASE (1974-2003), were conducted. Grey literature was hand searched and the reference lists of identified studies and reviews examined. The manufacturers of COMT inhibitors were contacted. SELECTION CRITERIA: Randomised controlled trials of adjuvant COMT inhibitor therapy versus a placebo in patients with a clinical diagnosis of idiopathic Parkinson's disease and long-term complications of levodopa therapy. DATA COLLECTION AND ANALYSIS: Data were abstracted independently by the authors and differences settled by discussion. The outcome measures used included Parkinson's disease rating scales, levodopa dosage, 'off' time measurements and the frequency of withdrawals and adverse events. MAIN RESULTS: Fourteen trials fulfilled the inclusion criteria. 2566 patients with Parkinson's disease and motor fluctuations were included in this review. Eight trials examined entacapone versus placebo in a total of 1560 patients. These trials were between two and twelve months in duration. Six trials examined tolcapone versus placebo in a total of 1006 patients. These trials were between six weeks and twelve months in duration. Both tolcapone and entacapone reduced 'off' time, reduced levodopa dose and modestly improved motor impairments and disability. This was at the expense of increased risk of dyskinesias, nausea, vomiting, and diarrhoea. A few participants taking tolcapone were found to have raised liver enzyme levels. REVIEWERS' CONCLUSIONS: In the management of the motor complications seen in Parkinson's disease, tolcapone and entacapone can be used to reduce off time, reduce levodopa dose, and modestly improve motor impairment and disability. This is based on, at best, medium term evidence. However some participants on tolcapone had raised liver enzymes. This combined with three cases of fatal hepatic toxicity found during post-marketing surveillance has raised concerns over the safety of tolcapone.

Antiparkinson Agents↗

Pramipexole in patients with Parkinson's disease and marked drug resistant tremor: a randomised, double blind, placebo controlled multicentre study.

OBJECTIVE: To compare the tremorlytic properties of pramipexole, a non-ergoline dopamine agonist to those of placebo as add on medication in patients with Parkinson's disease. METHODS: Eighty four patients with early or advanced Parkinson's disease and marked, drug resistant tremor under a stable and optimised antiparkinsonian medication were included in a double blind, randomised, placebo controlled, multicentre study and assigned to add on treatment (7 week dose titration interval, 4 week maintenance period) with either pramipexole (n=44) or placebo (n=40) as adjunct. The primary end point was the absolute change in tremor score, defined as the sum of tremor related items (16, 20, 21) of the unified Parkinson's disease rating scale (UPDRS) in "on" periods. Secondary end points included the percentage change in tremor score, the absolute and percentage changes in long term EMG tremor registration, and the change in tremor self rating scales. Safety and tolerability were assessed on the basis of adverse events, laboratory tests, ECG, and vital signs. RESULTS: Pramipexole was significantly superior to placebo with a difference between treatment groups in the mean absolute change in tremor score of -4.4 (95% confidence interval (95% CI) -6.2 to -2.5) (p<0.0001), corresponding to a difference in the mean percentage change of -34.7% in favour of pramipexole. The secondary end points were consistent with the significant change in tremor score and provided further evidence for the benefit of pramipexole compared with placebo. Long term EMG registration as an objective measure showed a difference in mean absolute change in tremor occurrence of -15.2% (95%CI -21.4 to -9.0) (p<0.0001), and a difference in the mean percentage change of -45.7% in favour of pramipexole. The treatment effects increased during dose titration and remained stable during the 4 week maintenance dose period until the end of the study. The average daily pramipexole dose during maintenance was 4.1 (SD 0.9) mg. Safety analysis showed an increased rate of fatigue, insomnia, nausea, abdominal pain, and headache under pramipexole, comparable with previous studies. CONCLUSION: Pramipexole proved to be an effective agent for patients with Parkinson's disease and drug resistant tremor.

Administration, Oral↗

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↗

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↗