Current clinical practice for Parkinson’s disease among Chinese physicians,general neurologists and movement disorders specialists: a national survey

Background

To explore current status and choices regarding diagnosis and treatment of Parkinson’s disease (PD) among physicians, general neurologists and movement disorders specialists in China via a national survey.

Methods

The cross-sectional questionnaire-based survey was conducted from November, 2010 to July, 2011. Six hundreds and twelve doctors from different cities in China were recruited for this study.

Results

68.6% (n=420) and 23.9% (n=146) of doctors have read the national and international guidelines, respectively. There was a larger proportion of movement disorders specialists reading the guidelines, in contrast to physicians and general neurologists (P<0.001). Up to 76.4% (n=465) and 81.8% (n=498) of doctors would choose standard oral levodopa test and conventional MRI(with T1 and T2), respectively; Whereas susceptibility weighed imaging(SWI)(16.1%; n=98), transcranial sonography (TCS) (1.8%; n=11) and functional neuroimaging test, such as single photon emission computed tomography(SPECT) (10.2%; n=62) and positron emission tomography(PET)(13.3%; n=81) were less used for suspected patients with PD in clinical practice. Doctors at different levels or from different hospitals and cities would choose different medication for motor complications and non-motor symptoms of patients with PD, in addition to initial drug selection for newly diagnosed PD. Doctors who had read the guidelines had significantly better knowledge of medication selections for PD under specific circumstances.

Conclusions

Compared with commonly employed standard oral levodopa test and conventional MRI, SWI complements MRI, TCS and functional neuroimaging were less performed for diagnosis of PD in clinical practice in China. The choices of diagnostic methods and therapeutic strategy of PD vary among physicians, general neurologists and movement disorders specialists. Guideline awareness is markedly beneficial to reasonable PD medications strategy in China.

     

Selective disorders of reading?

Over the past few decades, refined cognitive architectures with highly specific components have been proposed to explain apparently selective disorders of reading, resulting from brain disease or injury, in previously literate adults. Recent analysis of the more general linguistic and cognitive abilities supported by neural systems damaged in the various forms of alexia favours a rather different view of reading and the kinds of models sufficient to account for its acquisition, skilled performance and disruption.     

Alzheimer's disease: an intracellular movement disorder?

Axonal transport is essential for maintaining the structure and function of nerve cells. Deficient axonal transport has been implicated in several neurodegenerative diseases, including Alzheimer's disease (AD). In addition to a disturbed cytoskeleton and other abnormalities observed in AD that are suggestive of axonal transport deficits, several AD-related proteins are implicated in the regulation of axonal transport. A recent study has demonstrated that the axonal transport deficit occurs early in the course of AD, preceding amyloid pathology substantially in mouse models of AD; more importantly, the study showed that reduced axonal transport leads to increased amyloid beta production and deposition. These data place axonal transport deficits at a central point in the pathogenesis of AD.     

Turnip vein clearing virus movement protein nuclear activity: Do Tobamovirus movement proteins play a role in immune response suppression?

Plant viruses'' cell-to-cell movement requires the function of virally encoded movement proteins (MPs). The Tobamovirus, Tobacco mosaic virus (TMV) has served as the model virus to study the activities of single MPs. However, since TMV does not infect the model plant Arabidopsis thaliana I have used a related Tobamovirus, Turnip vein-clearing virus (TVCV). I recently showed that, despite belonging to the same genus, the behavior of the 2 viruses MPs differ significantly during infection. Most notably, MP^TVCV, but not MP^TMV, targets the nucleus and induces the formation of F actin-containing filaments that associate with chromatin. Mutational analyses showed that nuclear localization of MP^TVCV was necessary for TVCV local and systemic infection in both Nicotiana benthamiana and Arabidopsis. In this addendum, I propose possible targets for the MP^TVCV nuclear activity, and suggest viewing MPs as viral effector-like proteins, playing a role in the inhibition of plant defense.     

Orthobiologics in the treatment of hip disorders

Orthobiologics are biological materials that are intended for the regeneration or healing of bone,cartilage and soft tissues.In this review we discuss the use of orthobiologics for hip disorders providing an update.The orthobiologics included in this article are hyaluronic acid,platelet rich plasma,bone marrow,adipose tissue and expanded mesenchymal stem cells.We explain the concepts and definitions of each orthobiological product,and the literature regarding its use in the hip joint.The paucity of guidelines for the production and characterization of the biological products leads to uneven results across the literature.Each biologic therapy has indications and benefits;however,noteworthy are the characterization of the orthobiologics,the application method and outcome analysis for further improvement of each technique.     

Comorbid ADHD and mental health disorders: are these children more likely to develop reading disorders?

While attention-deficit/hyperactivity disorder (ADHD) has been associated with both internalizing and externalizing childhood behaviour disorders, the specific relationship of these comorbid disorders to ADHD and reading problems is less well defined. The present study analysed data from the Australian Twin ADHD Project, which utilized DSM-IV-based ratings of ADHD, separation anxiety disorder, generalized anxiety disorder, depression, conduct disorder, and oppositional defiant disorder for twins and siblings aged 6 to 18 years. While differences between children with and without ADHD were demonstrated for those with separation anxiety disorder, generalized anxiety disorder, depression, conduct disorder, oppositional defiant disorder and a reading disorder, for all age groups, regression analysis of ADHD diagnostic subtypes by age and reading disorder showed that only generalized anxiety disorder remained significant after controlling for ADHD subtypes. Analysis of the mean reading disorder scores in children with and without ADHD showed that children with conduct disorder had significantly more reading problems, as did children with multiple comorbid disorders. In summary, both age and ADHD diagnosis were associated with variations in these comorbid disorders, and multiple comorbid disorders were associated with greater reading impairment.     

What is complex about complex disorders?

Rather than being polygenic, complex disorders probably represent umbrella terms for collections of conditions caused by rare, recent mutations in any of a large number of different genes.     

Selection in favor of lysosomal storage disorders?

Four examples of Israeli communities or large families in which high consanguinity is common are presented, with two different lysosomal storage disorders within each community. In each of the four cases the stored substances share common chemical structure, despite the different lysosomal hydrolases involved in each disease. A similar phenomenon is known among the Ashkenazi Jews, in whom four of the most frequent hereditary disorders are lysosomal storage disorders, which are characterized by storage of sphingolipid derivatives. Similar findings are reported in the literature in other communities. We suggest that this phenomenon indicates a selection in favor of lysosomal storage disorders of similar nature in certain populations. The selection forces leading to this phenomenon have not been identified yet, and it has not yet been determined whether these forces are the same in the different communities presented here.     

What's next? Sequential movement encoding in primary motor cortex

Complex actions often can be decomposed into sequences of individual movements. Primate medial motor areas (SMA and pre-SMA) have been shown to be key players in the concert of such sequential actions. In this issue of Neuron, Lu and Ashe show for the first time that neurons in primate M1-the ultimate output stage of cortex-have anticipatory activity related to specific movement sequences. These findings challenge the traditional view of M1 as being a simple module for generating movements.     

American geneticists and the eugenics movement: 1905–1935

Conclusion I have attempted to show that between 1905 and 1935, both internal and external factors were important in producing and influencing geneticists' attitudes toward the eugenics movement. Internal factors operated in several ways during this period. In the first decade of the century, discoveries within genetics supplied geneticists a mode of expression to evoke their already existing social concern by providing a new vocabulary with which to present eugenic proposals. In addition, because these findings were relatively easy to explain to the layman, it became an easy matter for geneticists to popularize eugenics. After 1915, by suggesting the complexity of inheritance, other developments within genetics helped dim their initial enthusiasm for the movement. During this period, factors external to the science of genetics also were important. By producing a general interest in social affairs among many geneticists, the intellectual and social milieu of the late 1800's lay the foundations for their early participation in the eugenics movement. In the 1920's and 1930's the subjection of genetic theory to support preconceived social and political doctrines prompted them to renounce the movement publicly.While both internal and external factors operated on geneticists, the lesson of this study is that external factors were more important in influencing their attitudes toward the movement than internal factors. At the turn of the century, geneticists inherited from Social Darwinism a general interest in applying biological principles to the analysis of social problems; discoveries within genetics mainly provided a convenient and persuasive terminology with which to express their interest. Later, both internal and external factors caused their enthusiasm for the movement to wane, but their public renunciation of it was caused primarily by external factors alone.The importance of external factors is seen to be even greater by considering the model I suggested to explain the development of social responsibility in modern form among scientists. According to this model, social responsibility results after a crisis in the social uses of a given science—as a response to external factors. This model appears to account satisfactorily for the emergence of geneticists' sense of social responsibility: alarmed by eugenicists' frequent endorsement of Nazi eugenic programs, many geneticists claimed it was their duty to explain the facts of their science to the public so that the layman could see for himself the scientific errors of racism. Geneticists were now presenting the layman the facts, though not necessarily interpreting the facts for him. This same pattern—the emergence of modern social responsibility after an externally induced crisis-appears to be present in the other examples that I gave.The ironies revealed by this study are many. First, it is ironic that principles of genetics created feelings of both pessimism and optimism among many geneticists. Early developments in genetics-Mendel's laws, the concept of unit inheritance, and Weismann's theory-supplemented Social Darwinism in creating an atmosphere of pessimism among many geneticists by posing the grim assumption that human defects are hereditarily determined and incapable of medical cure. In recognizing the importance of heredity in development, many geneticists for a while were overly pessimistic in their forecasts of the evolutionary future of the human race. These same three genetic developments, however, by suggesting the feasibility of a eugenics program, of controlling reproduction to eliminate defective genes from the population, provided a remedy to the problem they had helped create.It is also ironic that even though the classical eugenics movement has been discredited in America for over thirty years, many individuals today are speaking of certain dangers to society in terms remarkably similar to those used by the classical eugenicists. The explosion of the atomic bomb created a sudden awareness among the public of the dangers of gene mutation from radiation and other sources⁴¹. Today, as topics such as the genetic load are increasingly discussed, many individuals are experiencing a growing alarm over the future genetic condition of the American people, a marked concern over the rising genetic and financial costs to society of modern medicine for preserving defectives and allowing them to reproduce.Although geneticists in the 1930's generally abandoned the ideal of using science to prescribe policy, to construct ends for social action, it was this ideal which initially attracted many of them to the eugenics movement in the first place. In the early years of the century, geneticists viewed science in a new light: as a restraint upon conduct. Hitherto, science had been valued for its products, for releasing man from old burdens, for supplying him new opportunities to enjoy and to explore life. In supporting the eugenics movement, geneticists departed from this mode. They now appealed to science, not for a particular product, but to determine who should and who should not reproduce. They let science act as a constraint upon their actions; they let science tell them that individual desires are less important than the biological and moral imperative of improving the human race⁴². Thus, it becomes understandable why many geneticists for a time regarded eugenics as a religion, for they had permitted biology to assume religion's traditional function of defining permissible conduct. The history of geneticists' involvement with the eugenics movement reminds us that science can play many roles and be put to many purposes.     

Simulated movement termination for balance recovery: can movement strategies be sought to maintain stability in the presence of slipping or forced sliding?

Slipping during various kinds of movement often leads to potentially dangerous incidents of falling. The purpose of this study was to determine whether there was evidence to support the theory that movement strategies could be used by individuals to regain stability during an episode of slipping and whether forced sliding from a moving platform accurately simulated the effect of slipping on stability and balance. A single-link-plus-foot biomechanical model was used to mathematically simulate base of support (BOS) translation and body segment rotation during movement termination in sagittal plane. An optimization routine was used to determine region of stability [defined at given COM locations as the feasible range of horizontal velocities of the center of mass (COM) of human subject that can be reduced to zero with respect to the BOS while still allowing the COM to traverse within the BOS limits]. We found some 30% overlap in the region of stability for slipping and non-slipping conditions. This finding supports the theory that movement strategies can be sought for restoring stability and balance even if slipping unexpectedly occurs. We also found that forced sliding produces effects on stability that are similar to those of slipping, indicated by over 50% overlap in the regions of stability for the two conditions. In addition, forced sliding has distinctive effects on stability, including a "shift" of the region of stability extended beyond the BOS in the direction of sliding. These findings may provide quantifiable guidance for balance training aimed at reducing fall incidents under uncertain floor surface conditions.     

Chemotaxis in pathogenic spirochetes: directed movement toward targeting tissues?

Chemotaxis is an important feature of motile organisms that allows navigation through various environments. It enables them to detect nutrients and to avoid unfavorable or dangerous conditions. Motility and chemotaxis are widely acknowledged as important virulence factors for pathogenic bacteria. In this review, we try to explore the role of chemotaxis in the pathogenesis of spirochetes. Chemotaxis might be involved in tissue identification and penetration, and represents a possible mechanism for evasion of the host's immune defense. The recent development of genetic tools for pathogenic spirochetes and "tracking" techniques, employing fluorescent in situ hybridization (FISH), could revolutionize our understanding of the importance of chemotaxis for infection and persistence of these bacteria in their host.     

Tenascins in fibrotic disorders—from bench to bedside

Although fibrosis is becoming increasingly recognized as a major cause of morbidity and mortality in chronic inflammatory diseases, available treatment strategies are limited. Tenascins constitute a family of matricellular proteins, primarily modulating interactions of cells with other matrix components and growth factors. Data obtained from tenascin C deficient mice show important roles of this molecule in several models of fibrosis. Moreover there is growing evidence that tenascin C has a strong impact on chronic inflammation, myofibroblast differentiation and recruitment. Tenascin C as well as tenascin X has furthermore been shown to affect TGF-β activation and signaling. Taken together these data suggest that these proteins might be important factors in fibrosis development and make them attractive both as biological markers and as targets for therapeutical intervention. So far most clinical research in fibrosis has been focused on tenascin C. This review aims at summarizing our up-to-date knowledge on the involvement of tenascin C in the pathogenesis of fibrotic disorders.     

How do Abl family kinases regulate cell shape and movement?

Genetic analysis and studies of normal and leukemia cells in culture have shown that Abl family nonreceptor tyrosine kinases regulate cell morphogenesis and motility. Abl family kinases, which include Drosophila (D-) Abl and the vertebrate Abl and Arg proteins, relay signals from cell surface growth-factor and adhesion receptors to promote cytoskeletal rearrangements. Recent biochemical and crystallographic analyses have clarified the mechanisms by which growth-factor and adhesion receptors might regulate the activity of Abl family kinases. When activated, Abl family kinases can regulate cytoskeletal dynamics by phosphorylating several known cytoskeletal regulatory proteins. In addition, the C-terminal half of Abl family kinases has several domains that bind to cytoskeletal components. Emerging evidence suggests that Abl family kinases can use these domains to directly organize cytoskeletal structure in vivo.     

Endophenotypes for psychiatric disorders: ready for primetime?

It is increasingly accepted that the imprecision of categorical psychiatric diagnoses can be a limiting factor in understanding the genetic basis of human behavioral abnormalities. Genetic investigation of endophenotypes--more precisely defined quantitative traits hypothesized to underlie disease syndromes--offers great promise as an alternative or complement to studies of categorical disease phenotypes. However, there is not yet standardization of the methods by which candidate endophenotypes should be chosen and applied. Fruitful endophenotype studies depend on the selection of heritable, quantitative traits that can be objectively and reliably measured. In this article, we propose guidelines for such investigations for psychiatric disorders, using endophenotypes previously proposed for bipolar disorder as particular examples. Gene expression studies and non-human primate models are recent developments in which an endophenotype approach might prove particularly valuable.     

Are culture-bound syndromes as real as universally-occurring disorders?

This paper asks what it means to say that a disorder is a "real" disorder and then considers whether culture-bound syndromes are real disorders. Following J.L. Austin I note that when we ask whether some supposed culture-bound syndrome is a real disorder we should start by specifying what possible alternatives we have in mind. We might be asking whether the reported behaviours genuinely occur, that is, whether the culture-bound syndrome is a genuine phenomenon as opposed to a myth. We might be wondering whether the condition should rightly be considered a disorder, as opposed to some sort of non-disorder condition (for example, a non-disorder form of deviance, or a potentially valuable condition). We might want to know whether the culture-bound syndrome is really a distinct disorder, in the sense that scientific classification systems should include it as a separate category, or whether it is just a variant of a universally occurring disorder. I argue that some specific difficulties can arise with determining whether a culture-bound syndrome is a real disorder in each of these three senses. However, the frequent assumption that real disorders will necessarily occur universally, and that those that occur only in certain environments are suspicious is not generally justified.