[Restless legs syndrome. Guidelines for diagnosis and therapy].
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Dopamine Agents↗
Biomedical subjects
W Hening
Publications and source records attributed to W Hening.
Procedural motor learning in Parkinson's disease.
We have been investigating motor control and learning in parkinsonian subjects. In the current study, we sought to explore the existence of deficits in procedural motor learning, which is a form of implicit motor learning where skill improves over repetitive blocks of trials. We sought to determine, in particular, whether any such deficit is accentuated during specific types or phases of learning. We would expect that those specific learning tasks would require the greatest participation of the basal ganglia. Numerous studies have found that Parkinson's disease (PD) patients may show deficits in learning. Combined with information about basal ganglia neuronal connections and activity, this led some investigators to suggest that one of the key functions of the basal ganglia is to facilitate learning. To investigate these learning deficits, we used a robotic device to generate conservative force fields that disturbed the subjects' arm movements, thereby generating a "virtual mechanical environment" that subjects learned to manipulate. Movements were successively grouped into blocks comprising five different conditions: motor performance, early learning, late learning, negative transfer, and aftereffect motor performance. Our results with eight right-handed PD subjects and nine age-matched controls showed a relative decrease in the rate of learning for the PD patients in all blocks, but greater differences emerged between groups during novelty phases of learning. In particular, the difference in performance during the negative transfer condition reached statistical significance, suggesting that the basal ganglia might be a key center for "switching" motor patterns. Our results support the hypothesis that deficiencies in procedural motor learning are characteristic of PD. They add to existing evidence which has suggested a key role for the basal ganglia when new sensorimotor mappings are required by novel task environments. Better understanding of these deficits should facilitate the rehabilitation of PD patients.
Aged↗
Long-term follow-up on restless legs syndrome patients treated with opioids.
The medical records of 493 patients with restless legs syndrome (RLS) from three major centers were studied to determine the number and outcome of patients who had been treated with opioids as a monotherapy. At one time or another 113 patients (51 men, 62 women; age range, 37-88 years) had been on opioid therapy either alone (36 patients) or with opioids added secondarily to other medications used to treat RLS (77 patients). Twenty-three of the 36 opioid monotherapy patients had failed dopaminergic and other therapeutic agents prior to the initiation of opioid monotherapy. Twenty of the 36 opioid monotherapy patients continue on monotherapy for an average of 5 years 11 months (range, 1-23 years), despite their knowledge of the availability of other therapies. Of the 16 patients who discontinued opioids as a sole therapy, the medication was discontinued in only one case because of problems related to addiction and tolerance. Polysomnography on seven patients performed after an average of 7 years 1 month of opioid monotherapy (range, 1-15 years) showed a tendency toward an improvement in all leg parameters and associated arousals (decrease in PLMS index, PLMS arousal index, and PLM while awake index) as well as all sleep parameters (increase in stages 3 and 4 and REM sleep, total sleep time, sleep efficiency, and decrease in sleep latency). Two of these seven patients developed sleep apnea and a third patient had worsening of preexisting apnea. Opioids seem to have long-term effectiveness in the treatment of RLS and PLMS, but patients on long-term opioid therapy should be clinically or polysomnographically monitored periodically for the development of sleep apnea.
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Automatic orienting of visuospatial attention in Parkinson's disease.
The basal ganglia are involved in not only motor behavior, but also other more cognitive processes, such as attention. We tested Parkinson's disease (PD) patients in a task that measures reflexive orienting of spatial attention. Seven patients with idiopathic PD and eight control subjects performed a covert orienting task where spatial attention was directed by means of exogenous cues (luminance increments) with no predictive validity for target position. The subjects' task was to make a speeded saccade to a visual target, which appeared a variable time after onset of the cue either in the cued or an uncued spatial position. There was no overall difference between PD patients and control subjects in terms of the initial facilitation following reflexive cues, and later inhibition of return (IOR). However, PD patients differed from control subjects in two important respects. First, they were significantly faster than were control subjects on this reflexive visual-orienting task. Second, disease severity correlated with attentional performance; more advanced patients showed less initial facilitation but greater IOR. Thus PD patients show better performance on a reflexive saccade task and, for more advanced patients, greater IOR than control subjects. These findings are consistent with the possibility that reflexive attentional processes in PD patients may be more active.
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The interaction of visual and proprioceptive inputs in pointing to actual and remembered targets in Parkinson's disease.
We previously reported that Parkinson's disease patients could point with their eyes closed as accurately as normal subjects to targets in three-dimensional space that were initially presented with full vision. We have now further restricted visual information in order to more closely examine the individual and combined influences of visual information, proprioceptive feedback, and spatial working memory on the accuracy of Parkinson's disease patients. All trials were performed in the dark. A robot arm presented a target illuminated by a light-emitting diode at one of five randomly selected points composing a pyramidal array. Subjects attempted to "touch" the target location with their right finger in one smooth movement in three conditions: dark, no illumination of arm or target during movement; movement was to the remembered target location after the robot arm retracted; finger, a light-emitting diode on the pointing fingertip was visible during the movement but the target was extinguished; again, movement was to the remembered target location; and target, the target light-emitting diode remained in place and visible throughout the trial but there was no vision of the arm. In the finger condition, there is no need to use visual-proprioceptive integration, since the continuously visualized fingertip position can be compared to the remembered location of the visual target. In the target condition, the subject must integrate the current visible target with arm proprioception, while in the dark condition, the subject must integrate current proprioception from the arm with the remembered visual target. Parkinson's disease patients were significantly less accurate than controls in both the dark and target conditions, but as accurate as controls in the finger condition. Parkinson's disease patients, therefore, were selectively impaired in those conditions (target and dark) which required integration of visual and proprioceptive information in order to achieve accurate movements. In contrast, the patients' normal accuracy in the finger condition indicates that they had no substantial deficits in their relevant spatial working memory. Final arm configurations were significantly different in the two subject groups in all three conditions, even in the finger condition where mean movement endpoints were not significantly different. Variability of the movement endpoints was uniformly increased in Parkinson's disease patients across all three conditions. The current study supports an important role for the basal ganglia in the integration of proprioceptive signals with concurrent or remembered visual information that is needed to guide movements. This role can explain much of the patients' dependence on visual information for accuracy in targeted movements. It also underlines what may be an essential contribution of the basal ganglia to movement, the integration of afferent information that is initially processed through multiple, discrete modality-specific pathways, but which must be combined into a unified and continuously updated spatial model for effective, accurate movement.
Aged↗
Controversies in sleep medicine.
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Journal Article↗
The brain decade in debate: VII. Neurobiology of sleep and dreams.
This article is a transcription of an electronic symposium held on February 5, 2001 by the Brazilian Society of Neuroscience and Behavior (SBNeC) during which eight specialists involved in clinical and experimental research on sleep and dreaming exposed their personal experience and theoretical points of view concerning these highly polemic subjects. Unlike most other bodily functions, sleep and dreaming cannot, so far, be defined in terms of definitive functions that play an ascribable role in maintaining the organism as a whole. Such difficulties appear quite clearly all along the discussions. In this symposium, concepts on sleep function range from a protective behavior to an essential function for maturation of the nervous system. Kleitman's hypothesis [Journal of Nervous and Mental Disease (1974), 159: 293-294] was discussed, according to which the basal state is not the wakeful state but sleep, from which we awake to eat, to protect ourselves, to procreate, etc. Dreams, on the other hand, were widely discussed, being considered either as an important step in consolidation of learning or simply the conscious identification of functional patterns derived from the configuration of released or revoked memorized information.
Animals↗
Controversies in sleep medicine.
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Journal Article↗
Controversies in sleep medicine.
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Journal Article↗
A novel quantitative method for 3D measurement of Parkinsonian tremor.
OBJECTIVE: To demonstrate the usefulness of a three dimensional (3D) motion analysis system for the quantitative measurement of tremor in patients with Parkinson's disease (PD). METHODS: Six PD patients with hand tremors were studied using a system that employed 3D electromagnetic position sensors to measure the actual, cumulative displacement of the tremoring finger. Patients were studied in different hand positions and activating conditions before and 30, 60, 90 and 120 min after intake of Pramipexole, a dopamine agonist known to reduce tremor. Tremor amplitude and frequency, before and after drug intake, were compared using Mann-Whitney U test and Wilcoxon rank test, respectively. RESULTS: The motion analysis system allowed discrimination of tremor related events from movement artifact and allowed the calculation of real world movement of the finger tremor despite altered hand positions and orientation. Average 3D tremor frequency ranged from 3.71 to 4.34 Hz. Median tremor amplitude (total distance traveled per 5 s interval) decreased with drug from 4.9 to 1.6 cm for resting tremor, 4.5 to 3.7 cm for postural tremor, 3.4 to 3.3 cm for precision tremor, 10.2 to 3.3 cm for tapping activation and 108.6 to 5.7 cm for counting activation. CONCLUSIONS: Our method of 3D analysis provides a robust, single quantitative measure of tremor amplitude that is intuitive and likely to reflect the functional impact of tremor. This methodology should be useful in comparing tremor across patients and in measuring the efficacy of therapeutic interventions.
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The treatment of restless legs syndrome and periodic limb movement disorder. An American Academy of Sleep Medicine Review.
A task force consisting of six authors reviewed the published literature on the therapy of the restless legs syndrome or periodic limb movements in sleep available in indices through April, 1998. They selected the 45 articles for detailed review which presented original investigations of therapeutic impact on the restless legs syndrome (RLS) or periodic limb movements (PLM) and which met minimal standards. These articles dealt with a range of pharmacological and other treatment modalities, although most dealt with medications and almost half of those concentrated on dopaminergic agents, especially levodopa in various formulations. Almost half of the articles reviewed used controlled methodologies, most commonly cross-over methodologies with randomized allocation of subjects. Multi-center studies with large numbers of subjects and long-term controlled studies were not found. Information was extracted from the articles and study design, clinical definition, evaluative measures, side effects, and outcomes were tabulated in 6 evidence tables and summarized in the accompanying text. This literature was evaluated for the nature of the studies performed and its coverage of potential therapies. The review concludes with comments on possible future directions for therapeutic investigation based on the current state of the literature.
Diagnosis, Differential↗
Control of voluntary and reflexive saccades in Parkinson's disease.
Eight patients with idiopathic Parkinson's disease (PD) were compared with a group of age-matched controls on both reflexive saccade and antisaccade tasks. While reflexive, visually guided saccades led to equivalent performance in both groups, PD patients were slower, made more errors, and showed reduced gain on antisaccades (AS). This is consistent with previous results showing that PD patients have no difficulty with reflexive saccades but show deficiencies in a number of voluntary saccade paradigms. Moreover, visual information in the form of landmarks improves AS performance more for PD patients than controls, a finding analogous to results seen with other motor acts such as target-directed pointing. Results are discussed in terms of a two-process model of attention and eye movements.
Aged↗
Pointing to remembered targets in 3-D space in Parkinson's disease.
A three-dimensional tracking system was used to examine whether subjects with Parkinson's disease (PD) would show characteristic performance deficits in an unconstrained pointing task. Five targets were presented in a pyramidal array in space to 11 individuals with mild to moderate PD and 8 age-matched controls. After the target was indicated, subjects closed their eyes and pointed to the remembered target locations without vision. Despite the absence of visual feedback during movement, PD subjects were as accurate overall as controls. However, PD subjects showed greater variable errors, more irregular trajectories, and a vertical endpoint bias in which their endpoints were significantly lower than controls. They also showed deficiencies in the compensatory organization of joint rotations to ensure consistency in azimuthal (horizontal) positioning of the arm endpoint. We concluded that, under appropriate task conditions, PD subjects may not show overall deficits in accuracy even when making targeting movements at normal speed without visual feedback. Nevertheless, our findings indicate that there are certain dimensions of performance which are selectively altered in Parkinson's disease even when overall performance is normal.
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Periodic limb movements and restless legs syndrome.
The criteria that characterize restless legs syndrome (RLS) and the differential diagnoses are discussed. Clinical signs include sleep disturbance, involuntary movements in sleep or wakefulness, a normal neurologic examination, a chronic clinical course, and, in some cases, a positive family history. Periodic limb movements during sleep, which also may occur as an isolated finding, may or may not cause frequent arousals or awakenings. Clinical diagnosis of idiopathic or symptomatic forms of RLS can be supported with polysomnography. Treatment of first choice consists of dopaminergic drugs or dopamine agonist followed by opioids or benzodiazepines.
Adult↗
A questionnaire study of 138 patients with restless legs syndrome: the 'Night-Walkers' survey.
After verifying the diagnosis of restless legs syndrome (RLS) in 105 patients who are part of a nationwide support group, we undertook a telephone survey of their symptomatology. We then compared the answers with those of 33 of our own RLS patients who had undergone a neurologic examination and had a periodic limb movement in sleep (PLMS) index of > 5 (number per hours of sleep). Although RLS has generally been considered to be a condition of middle to older age, the results for the support group, and for our patients, are similar in that more than a third of the patients in each group experienced their first symptoms before the age of 10. Initial lack of diagnosis or misdiagnosis by a physician were common and the symptoms were commonly thought to be psychogenic whatever the age of onset. In some cases, young age-onset RLS was severe from the start. For younger age-onset patients whose symptoms were severe enough to seek immediate medical attention, confounding or misdiagnosis included "growing pains" and attention deficit hyperactivity disorder. However, medical attention was generally not sought until the fourth decade. Most respondents stated that this was because their symptoms were mild at onset and then progressed. In the older age-onset patients, misdiagnoses also included skin irritation, arthritis, and malingering. A total remission of symptoms of a month or more was present in at least 15% of the individuals in all groups surveyed. More than 50% of the respondents know of one or more first-degree relatives affected by RLS. Five of our 33 patients had RLS initially triggered either by diabetic peripheral neuropathy or lumbosacral radiculopathy.
Adult↗
Magnetic brain stimulation: safety studies.
We describe short-term and long-term safety studies after low repetition rate magnetic brain stimulation in 10 normal subjects. We obtained quantitative EEG data, psychometric test results, serum prolactin and cortisol levels before and after brain stimulation. EEG and psychometric data were also obtained in 5 of these subjects 16-24 months after the initial experiment. Short- and long-term studies did not show any deleterious effects. Randt delayed recalls, however, showed a transient reduction in the score immediately after stimulation which resolved on retesting in 2 weeks. To address the question of fatigue we repeated Randt tests in 4 subjects before and after magnetic brain stimulation but without the other extensive psychometric, EEG and blood tests. Pre- and post-stimulation scores on this occasion showed no significant difference in these 4 subjects suggesting that the transient changes in the previous Randt score were related to fatigue. We conclude that single-pulse magnetic brain stimulation has no deleterious effects after magnetic brain stimulation.
Adult↗
Persistent movement disorders induced by buspirone.
Buspirone, an azospirone compound, is a nonsedative anxiolytic that has achieved wide usage since its introduction in 1987. Although relatively free of side-effects, there have been several instances of dyskinesia and dystonia associated with the use of buspirone. We report two patients with persistent movement disorders that developed after prolonged treatment with the drug. One patient developed a lasting problem of cervical-cranial dystonia and tremors after treatment with buspirone at a dosage of 40 mg/day for several weeks. Another, receiving 30 mg/day for 6 weeks, experienced an exacerbation of preexisting spasmodic torticollis and tardive dyskinesia as well as the onset of involuntary phonations. As shown by these and other examples, buspirone poses the risk for inducing or exacerbating several types of movement disorders.
Antipsychotic Agents↗
Human startle reflex: technique and criteria for abnormal response.
Because quantitative norms for the normal audiogenic startle response to repeated stimuli have not been previously reported, we now describe a technique for eliciting the startle response and analysing its habituation with repeated stimuli. We used binaural 105 dB tones delivered in 5 blocks of 4 tones. Successive blocks were separated by a 5 min period without tones stimuli and had progressively shorter inter-stimulus intervals (ISIs) beginning with 5 min in the first block and reducing to 1 min in the final, fifth block. We contrast the response and its habituation in a group of 8 normal subjects with that in a patient with clinically exaggerated startle. Based on the differences observed, we propose that the following criteria may be used to ascertain an abnormally increased startle response: (1) excessive duration of the myogenic response; (2) persistence of extracranial responses after the initial two blocks of stimuli; and (3) reduced habituation of the response (as measured by decreases in response duration and in the area under the curve of rectified EMG for the orbicularis oculi myogenic response). Our patient was abnormal on each of these measures. This result is consistent with past qualitative reports which have indicated that abnormal startle is associated both with excessive startle and with subnormal habituation. Study of further patients with hyperekplexia will be necessary to either confirm our data or modify our proposed criteria.
Acoustic Stimulation↗