Patients review: drug-induced movement disorders

Objective of this paper is to review drug-induced movement disorders (D-IMD) treated patients on Department of Neurology in University Hospital Osijek. We reviewed patients treated during 10 years period (from 1992 to 2002). Analysed group consisted of 14 patients. Reasons for hospitalisation were swallowing problems in 6 patients, neuroleptic malignant syndrome (NMS) in 3 patients, stroke in 2 patients, bolus choking in 2 patients, and speech disturbance in 1 patient. Working diagnosis for most of our patients was neurological disease, yet only later D-IMD diagnosis was established excluding primary neurological disease, or as associated disease to basic neurological disorder. Nine patients have diagnosed as Parkinson syndrome, 3 patients as NMS, and 4 as orolingual dyskinesia, either autonomously, or in combination with Parkinson syndrome. D-IMD was most frequently caused by neuroleptics. Thus the small number of patients hospitalised regarding this syndrome on Department of Neurology.     

Integrating music in breathing training and relaxation: II. Applications

Psychophysiological observations, especially PETCO2 and EEG, during relaxation training with deep-diaphragmatic breathing and mental imagery, suggest that the addition of certain types of music "deepens" breathing and quickens relaxation: PETCO2 "normalizes" with decreased respiration rate, and EEG shows decreased average theta and increased alpha. The combined psychophysiological indices suggest that music potentiates the hypometabolic counterarousal state. And clients unanimously report that they enjoy it.     

Integrating music in breathing training and relaxation: II. Applications

Psychophysiological observations, especially PETCO2 and EEG, during relaxation training with deep-diaphragmatic breathing and mental imagery, suggest that the addition of certain types of music deepens breathing and quickens relaxation: PETCO2 normalizes with decreased respiration rate, and EEG shows decreased average theta and increased alpha. The combined psychophysiological indices suggest that music potentiates the hypometabolic counterarousal state. And clients unanimously report that they enjoy it.     

Gene therapy technology applied to disorders of glucose metabolism: promise,achievements, and prospects

Gene transfer technology has spawned an entire realm of clinical investigation, collectively referred to as "gene therapy." The feasibility and achievements of gene therapy to prevent and treat glucose homeostasis disorders, with particular emphasis on diabetes mellitus, are evaluated in this review. While a considerable amount of effort has yielded gene delivery vectors based on adenoviral, retroviral, and herpes simplex virus DNA, the number of successful clinical applications has not been as impressive. Despite the number of successes in vitro and in animal models, preliminary safety trials in humans have not yet been attempted. The current state of this science, outlined here, underlines the necessity of marrying gene transfer technology with cell therapy. The ex vivo transfer of gene combinations into a variety of cell types will likely prove more therapeutically feasible than direct in vivo vector transfer. Current efforts aimed at assessing the future of gene therapy for diabetes must, at the very least, take into account the importance of moving successful methods into human safety trials.     

Cost-benefit analysis in patients with sleep-related breathing disorders - diagnosis and ncpap therapy during medical rehabilitation]

In a multi-centre study, 745 patients undergoing internal medical rehabilitation (for hypertension, coronary heart disease, gastrointestinal and respiratory diseases) were investigated. The health economic benefit was evaluated during the 3 weeks of medical rehabilitation, during which a sleep-medical diagnostic work-up and treatment were applied. Ambulatory screening for sleep-related breathing disorders was carried out in all patients. In positive cases (Apnoea-Hypopnoea Index > or = 10) transfer to our sleep lab was recommended. 103 patients were found to be positive, of whom 47 attended the lab; 23 of these accepted nCPAP therapy, while 24 did not. The costs of the additional diagnosis and treatment were considered incremental costs--and the benefit identified as the decrease in days off work as revealed by a comparison of the year before with the year after rehabilitation. Days off work decreased by 38.4 days in the treated group, and increased by 25.4 days in the untreated group. The results were extrapolated to all patients in internal medical rehabilitation in Germany, and a cost-benefit analysis showed that the benefit of expanding the additional investigation to cover all patients would far exceed the incremental costs in the first year after rehabilitation by 58.26 Mio [symbol: see text] and in the second year by 81.15 Mio. [symbol: see text].     

Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns

Background  

Neuroleptic-induced movement disorders (NIMDs) have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry.     

Basal ganglia oscillations and pathophysiology of movement disorders

Low frequency rest tremor is one of the cardinal signs of Parkinson's disease and some of its animal models. Current physiological studies and models of the basal ganglia differ as to which aspects of neuronal activity are crucial to the pathophysiology of Parkinson's disease. There is evidence that neural oscillations and synchronization play a central role in the generation of the disease. However, parkinsonian tremor is not strictly correlated with the synchronous oscillations in the basal ganglia networks. Rather, abnormal basal ganglia output enforces abnormal thalamo-cortical processing leading to akinesia, the main negative symptom of Parkinson's disease. Parkinsonian tremor has probably evolved as a downstream compensatory mechanism.     

Deep brain stimulation for movement and other neurologic disorders

Deep brain stimulation (DBS) was introduced as a treatment for patients with parkinsonism and other movement disorders in the early 1990s. The technique rapidly became the treatment of choice for these conditions, and is now also being explored for other diseases, including Tourette syndrome, gait disorders, epilepsy, obsessive-compulsive disorder, and depression. Although the mechanism of action of DBS remains unclear, it is recognized that DBS works through focal modulation of functionally specific circuits. The fact that the same DBS parameters and targets can be used in multiple diseases suggests that DBS does not counteract the pathophysiology of any specific disorder, but acts to replace pathologic activities in disease-affected brain circuits with activity that is more easily tolerated. Despite the progress made in the use of DBS, much remains to be done to fully realize the potential of this therapy. We describe some of the most active areas of research in this field, both in terms of exploration of new targets and stimulation parameters, and in terms of new electrode or stimulator designs.     

Recent physiological and pathophysiological aspects of Parkinsonian movement disorders

Deficits in the neural control of limb movements constitute a major part of Parkinsonian symptoms and are linked to a decay of dopaminergic neurotransmission. In animal models, Parkinsonian-like hypokinesia is consistently reproduced with large nigrostriatal dopamine depletions, while tremor and rigidity are less readily obtained. Lesions leading to a less than 70% striatal dopamine depletion are largely compensated by an increased activity of dopamine terminals. With more important lesions, supersensitivity of striatal non-adenylate cyclase-linked dopamine receptors occurs. Electrophysiological studies in Parkinsonian patients demonstrate increased reaction times and a reduced build-up of movement-related muscular activity underlying hypokinesia and provide circumstantial evidence for a central origin of tremor and rigidity. Single cell activity in unlesioned, behaving monkeys shows an increasingly direct relationship to movements when following the neural connections from mid-brain dopamine cells via striatum, globus pallidus, thalamus to pyramidal tract neurons of motor cortex. These data corroborate experimentally the concept that Parkinsonian hypokinesia is due to a failure of basic behavioral activating mechanisms.     

Hypoxia, hyperoxia and breathing

Conclusions This short Commentary has been limited to a few of several studies. They clearly indicate that the mechanisms involved in the effects of hypoxia and hyperoxia on the ventilatory control and particularly on theintegrative respiratory centres are far from being completely understood and are now believed to be more complex than what was postulated 40 years ago. Other mechanisms, which are beyond the scope of this short review, are currently the subjects of numerous studies which suggest that mediators or modulators are involved not only at the periphery but also at the level of the central nervous system. It must be emphasized that all these recent studies do not contradict at all, but rather help to explain, the early findings of Pierre Dejours concerning the participation of the peripheral chemoreceptors in the regulation and control of breathing.     

Breathing pattern and growth: comparative aspects

Summary The resting oxygen consumption and breathing pattern of nine newborn and adult species (ranging in body size from mouse to human) have been compared on the basis of data collected from the literature. Minute ventilation is similarly linked to at both ages, the percent of extracted as O₂ about 2.2. Tidal volume/kg is an interspecies constant in newborns and adults, approximately 8 ml/kg. Breathing frequency decreases with the increase in size in a different way at the two ages: large species have newborns breathing at rates 2–3 times above the corresponding adults' values, while in the small species newborns and adults breathe at almost the same rate. Therefore the newborns of the smallest species have both and below the expected values, implying a greater inability to cope with the external demands than newborns of larger species. Several considerations indicate that in the smallest newborns the mechanical properties of the respiratory system could be a constraint to resting ventilations larger than observed. It is therefore possible that their low is the cause, and not the effect, of the relatively small .     

Systems-level studies of movement disorders in dystonia and Parkinson's disease

For many years pathophysiological studies on patients with movement disorders were viewed as inferior to those in animal models because, given the complexity of dealing with the complete interconnected CNS, it was difficult to assign any particular physiological abnormality exclusively to the site of a known lesion. More recently this has come to be seen as an advantage. All the articles reviewed below focus on how healthy parts of the CNS react to damage at a distance, with the result that we are now beginning to have much more insight into how these reactions both compensate and exacerbate the primary deficit.     

Impediments to replication fork movement: stabilisation, reactivation and genome instability

Maintaining genome stability is essential for the accurate transmission of genetic material. Genetic instability is associated with human genome disorders and is a near-universal hallmark of cancer cells. Genetic variation is also the driving force of evolution, and a genome must therefore display adequate plasticity to evolve while remaining sufficiently stable to prevent mutations and chromosome rearrangements leading to a fitness disadvantage. A primary source of genome instability are errors that occur during chromosome replication. More specifically, obstacles to the movement of replication forks are known to underlie many of the gross chromosomal rearrangements seen both in human cells and in model organisms. Obstacles to replication fork progression destabilize the replisome (replication protein complex) and impact on the integrity of forked DNA structures. Therefore, to ensure the successful progression of a replication fork along with its associated replisome, several distinct strategies have evolved. First, there are well-orchestrated mechanisms that promote continued movement of forks through potential obstacles. Second, dedicated replisome and fork DNA stabilization pathways prevent the dysfunction of the replisome if its progress is halted. Third, should stabilisation fail, there are mechanisms to ensure damaged forks are accurately fused with a converging fork or, when necessary, re-associated with the replication proteins to continue replication. Here, we review what is known about potential barriers to replication fork progression, how these are tolerated and their impact on genome instability.     

Hypoxic Reptiles: Blood Gases, Body Temperature and Control of Breathing

Our contribution to this symposium is a review of recent modelsand experimental cdata on oxygen homeostasis in vertebrateswith normal intracardiac shunts; i.e., amphibians and reptiles.We focus on the interactions among hemoglobin function, bodytemperature regulation, and cardiovascular shunts under normalconditions (i.e., breathing fresh air at or near sea level)and during external hypoxia (e.g., altitude, burrows) and internalhypoxia (e.g., anemia, hemorrhage). Mathematical models andexperimental data suggest that animals with venous admixturefrom cardiovascular shunts will show biphasic arterial and mixedvenous Po₂ responses to warming; i.e., first increasing andthen, as the dissociation curve shifts too far to the right,decreasing. This has implications for many physiological functionsincluding oxygen consumption by tissues, control of breathing,as well as preferred body temperature and its regulation. Wepresent some of the recent experiments that have explored theseimplications.     

Anti-inflammatory and surgical therapy of olfactory disorders related to sino-nasal disease

Olfactory loss may be caused by mechanical obstruction or inflammation of the olfactory epithelium due to allergic/non-allergic rhinitis and chronic sinusitis with or without polyps. Treatment of olfactory loss related to sino-nasal disease is possible. Apart from surgical approaches and/or treatment with antibiotics, both systemic and topical steroids are effectively used in the therapy of olfactory loss related to sino-nasal disease. In most cases improvement of olfactory function appears to relate to the anti-inflammatory actions of the steroids used. While some details of therapeutic effect and dose regimen are not clear, systemic steroids are often helpful even in patients without nasal obstruction due to polyps or obvious inflammatory changes.     

Ostracism,voice, and exit: The biology of social participation

A bewildering variety of social patterns can be described and analyzed as manifestations of ostracism and social rejection. Ostracism can be viewed as a coerced or involuntary rupture of social bonds, as distinguished from voluntary exit; both appear to be characteristic ways that animals use in relating to other members of the group. Based on Albert O. Hirschman's Exit, Voice and Loyalty, a general theoretical framework can be built on the realization that ostracism is far from a strange aberration—but that its excesses strike most moderns as uncivilized. This analysis presumes that active participation, flight, and bonding are general categories intrinsic to social behavior. It follows that, in different social contexts, the implications of ostracism vary greatly. Modern democratic systems, in which voluntary exit remains a possibility, resemble our hominid past more closely than authoritarian societies that place individuals in the unenviable position of being trapped in silence (with no legitimate right to exercise political voice, yet no possibility of escape). At the risk of Charges of valuative bias, the argument is made that democratic regimes may be—all things equal—closer to the center of our species-typical range of behavior than other kinds of centralized states or governmental systems.