Pharmacotherapy of Parkinson's disease in Germany.

Treatment standards or guidelines have been developed for most features of Parkinson's disease (PD). However, data on the actual treatment that is put into practice are scarce. In 2000, a nationwide survey on the topic of sudden onset of sleep (SOS) in PD was initiated among the members of the German patient support group (deutsche Parkinson-Vereinigung, dPV). A part of this mailed questionnaire survey covering the antiparkinsonian and concomitant medication of the participants is presented here. This study analyses data sets from more than 6,500 PD patients. The mean dopaminergic dose was equivalent to 599 +/- 387 mg levodopa/die. The most frequently administered drugs were levodopa (94.2 %), dopamine agonists (DA) (71.7 %), amantadine (40.1 %), selegiline (27.6 %), entacapone (20.4 %), budipine (12.3 %), and anticholinergics (11.8 %). Costs of pharmacotherapy were estimated to be approximately 399 million/year in Germany. PD drug therapy in general strongly depended on age, disease duration, and the level of care. The treatment guidelines were apparently not consistently followed underlining the need for their continuous propagation throughout the medical community. In addition our data suggest that non-motor symptoms in PD are not adequately treated and that concomitant sedative medication contributes to the occurrence of SOS.

The alcohol-related accident risk in Germany: procedure, methods and results.

This paper presents the first reliable estimation of the alcohol-related accident risk in Germany by comparing a representative sample of accidents to a representative sample of trips not leading to a crash. The information about the trips was taken from the German Roadside Survey 1992-1994 (n=9087) conducted in Unterfranken, part of Bavaria. These data were weighted according to a representative study of driving in Germany (KONTIV 89). The accident study comprises a representative sample of accidents in Unterfranken in 1993 (n=1968). Relating accident risk to BAC, the global risk function indicates an exponential increase of accident risk for BACs above 0.05%. Controlling for correlating factors leads to an overall lower estimation with, however, the same structure, indicating that alcohol is consumed by drivers in circumstances which further increase the risk introduced by alcohol. Analyzing the attributable risk (AR) shows that about 12% of all accidents are attributable to alcohol. Over 96% of these happen with BACs of 0.05% and above. Thus, measures aimed at reducing the alcohol-related accident risk must focus on larger BACs, especially of 0.08% and above.

["Sleep attacks" in Parkinson patients. A side effect of nonergoline dopamine agonists or a class effect of dopamine agonists?]. / "Schlafattacken" bei Parkinson-Patienten. Eine Nebenwirkung von Nonergolin-Dopaminagonisten oder ein Klasseneffekt von Dopamimetika?

Recently, sudden "sleep attacks" have been described in parkinsonian patients taking the nonergoline dopamine agonists pramipexole and ropinirole. Due to this possible side effect, patients must be instructed not to drive vehicles and to refrain from other activities carrying the risk of self-injury. However, the very existence of sleep attacks remains controversial in sleep medicine, since a gradual transition from wakefulness to sleep is normally observed. Accordingly, sudden onset of sleep, e.g., in narcolepsy or sleep apnea syndrome, is usually associated with excessive daytime sleepiness. Prevalence of sleep disorders and daytime sleepiness have been shown to be increased in Parkinson's disease. Nonergoline dopamine agonists are already known to induce somnolence. Currently, it is not predictable whether sleep attacks represent a sudden transition from wakefulness to sleep or result from an increased propensity to fall asleep, with patients perceiving a sudden onset. Possible pathophysiological mechanisms and legal implications of sleep attacks are discussed.

[Hyperkinetic syndrome and behavioral disorders in street traffic: a case control pilot study]. / Hyperkinetisches Syndrom und Auffälligkeiten im Strassenverkehr: Eine fallkontrollierte Pilotstudie.

In the present pilot study we addressed the question of whether young people diagnosed with attention deficit hyperactivity disorder (ADHD) as children violate traffic regulations and are involved in traffic accidents more frequently than those in a control group without previous psychiatric disorders. The subjects in the ADHD group tended to be involved in traffic accidents more frequently than those in the control group. Furthermore, they had a significantly higher rate of involvement in traffic accidents before getting their driver's license. The two groups did not differ in the number of traffic violations, alcohol consumption or various attitudes related to driving. Split attention and reactive endurance were assessed with a computer-aided program. The ADHD group partly did significantly worse than the control group. Deficits on such performance measures and a lack of cognitive control in traffic may therefore be mediating factors for being accident-prone in traffic. Regardless of which group subjects were in initially, those reporting severe ADHD symptoms at the time of the study tended to be at an increased risk of causing traffic accidents and of being involved in more than one accident.

L-dopa therapy of uremic and idiopathic restless legs syndrome: a double-blind, crossover trial.

We report the effects of a single bedtime dose of L-dopa 100-200 mg on sleep quality, frequency of periodic leg movements (PLM) and daily living in patients with idiopathic and uremic restless legs syndrome (RLS). Seventeen patients with idiopathic and 11 with uremic (on continuous hemodialysis) RLS were evaluated comparatively by polysomnography, actigraphy and subjective ratings in a randomized, controlled and double-blind crossover trial with L-dopa and placebo for 4 weeks each. Neurophysiologic assessments showed significant reduction of the number of periodic leg movements (p = 0.003) and the PLM-index (p = 0.005) most pronounced during the first 4 hours of bedtime after L-dopa (p = 0.001). Subjective evaluation confirmed improvement of sleep quality (p = 0.002) and showed significantly higher quality of life during daytime (p = 0.030) while the patients received L-dopa therapy. We conclude that L-dopa 100-200 mg proved to be effective in idiopathic RLS and for the first time under controlled conditions in uremic RLS without any severe side effects.

New actigraphic assessment method for periodic leg movements (PLM).

A new actigraphic method by which periodic leg movements (PLM) can be measured is presented. Data acquistion and analysis were brought into line to distinguish short-lasting repetive leg movements from random motor restlessness. The definition of PLM follows the generally accepted criteria for PLM scoring. Thirty restless legs patients, all also suffering from PLM, were investigated three times by polysomnography, including tibialis anterior surface electromyography and actigraphy. A high correlation (reliability) was found for the number of PLM per hour spent in bed between the two methods. Furthermore, the actigraph records PLM specifically. An index of random motor restlessness is not sufficient for a reliable PLM according. In addition, periodic movements in sleep (PMS) and PLM show comparable variability in general. The actigraphic assessment of PLM, however, gives a better measure because PMS recordings may result in a substantial underestimation of PLM when sleep efficiency is reduced. This method is an ambulatory assessment tool that can also be used for screening purposes.

[Absolute driving incapacity at 1.0 promille--an erroneous limit]. / Absolute Fahruntüchtigkeit bei 1.0 Promille--die falsch gesetzte Grenze.

Following a well known decision of the Bundesgerichtshof (BGH, German Federal Court) a driver with a blood alcohol concentration (BAC) of more than 0.13% is seen as "absolutely unfit for driving" and will be prosecuted by criminal law. This decision was based on the results of a comprehensive review of the literature about the effects of alcohol done 1966 by the Bundesgesundheitsamt (BGA, National Bureau of Health). There, severe impairments were described at levels above 0.1%, a value which the BGH "rounded up" to 0.11%. The possible errors of measurement were estimated as 0.02%. Adding both values yielded the legal limit of 0.13%. Most recently Salger (vice-president of the BGH) in a decisive manner pleaded for a reduction of this limit to 0.11% both by lowering the assumed measurement error to 0.01% and by taking back the rounding-up operation. Explicitely he based these intended corrections of the former decision on two arguments he derived from the scientific research on alcohol and driving: 1. Significant impairments are linked with BACs higher than 0.1%. 2. This was demonstrated by road-side studies, studies with instrumented cars, and driving simulators which are more valid methods to predict driving behavior than studies conducted in the laboratory. We proved these assumptions by analyzing the literature about driving studies as well as the literature from laboratory studies on alcohol. This article mainly concentrates on the empirical results coming from driving studies. It demonstrates a clear-cut empirical evidence that no single limit can be determined from where alcohol-induced impairment begins. Quality and quantity of this impairment strongly depends on how difficult the driving situation actually is. Therefore, BAC and situational difficulty act together in a synergistic way. A driver only confronted with standard traffic situations which are easy to handle may react correctly despite a BAC of 0.1% and quite more. If difficulty is slightly augmented to situations where a more controlled and/or precision-oriented non-automatic driving is required, significant impairments were seen at levels of 0.07%. In traffic situations with unpredictable events and/or extreme driving conditions severe impairments are found even at levels below 0.05%. These results perfectly match with the results from the laboratory studies. As a consequence, any public policy decision as to the acceptable legal limit of alcohol has to include a decision as to the difficulty of traffic situations which has to be mastered by the driver. Claiming that a normal driver has to deal efficiently with a medium level of difficulty the scientific evidence demands a legal limit of about 0.07%.

Speech chronemics--a hidden dimension of speech. Theoretical background, measurement and clinical validity.

The term "speech chronemics" is introduced to characterize a research strategy which extracts from the physical qualities of the speech signal only the pattern of ons ("speaking") and offs ("pausing"). The research in this field can be structured into the methodological dimension "unit of time", "number of speakers", and "quality of the prosodic measures". It is shown that a researcher's actual decision for one method largely determines the outcome of his study. Then, with the Logoport a new portable measurement device is presented. It enables the researcher to study speaking behavior over long periods of time (up to 24 hours) in the normal environment of his subjects. Two experiments are reported. The first shows the validity of articulation pauses for variations in the physiological state of the organism. The second study proves a new betablocking agent to have sociotropic effects: in a long-term trial socially high-strung subjects showed an improved interaction behavior (compared to placebo and socially easy-going persons) in their everyday life. Finally, the need for a comprehensive theoretical foundation and for standardization of measurement situations and methods is emphasized.

Tranquillizer effects in an experimental analog of group psychotherapy.

In an experimental analog of group psychotherapy situations, the effects of two dosages of a tranquillizing agent (prazepam) are compared with those of placebo treatment. Pulse frequency and psychic strain on 24 healthy young volunteers was measured in different social interactions. Variations of social situations induced great changes both in physiological and in psychological measures. The drug acted differentially as to sex and dosage, but showed no situation-specific action. These and further results indicated that group dynamics are an efficient tool in proving drug effects.

Tranquillizer effects in an experimental analog of verbal examinations.

In an experimental analog of verbal examinations, the call-up situation, the effects of two dosages of a tranquillizing agent (lopirazepam) are compared to placebo treatment. 72 male and female, healthy, young volunteers have been randomly assigned to 12 groups of 6 subjects each. Pulse frequency and performance were registered. The results indicated differential drug effects which were interpreted according to the hypotheses of 'differential effects of social stressors'. If a situation was highly challenging for a subject, the application of a tranquillizer in an adequately high dosage enabled him to perform well in spite of or because of strong increases in pulse frequency.