The diagnosis of dystonia, an issue yet to be solved

Due to the lack of validated diagnostic biomarkers, the diagnosis of dystonia is based on clinical examination and therefore may be challenging and open to bias. The factors contributing to misdiagnosis of dystonia can be summarized in two main points: i) the huge variability in the clinical phenomenology of dystonia; ii) the existence of a bunch of medical conditions (i.e., pseudodystonia) mimicking the abnormal postures/movements induced by dystonia. This work is organized in two different part (Study 1 and Study 2) and the overall aim of the work is to help clinicians to better diagnosis idiopathic dystonia and functional dystonia. The objective of Study 1 is to identify clinical features suggestive of functional dystonia to guide physicians to distinguish functional dystonia from idiopathic dystonia. For this purpose, patient data were extracted from the Italian Registry of Functional Motor Disorders and the Italian Registry of Adult Dystonia. Patients with functional and idiopathic dystonia were followed up at the same clinical sites, and they were similar in age and sex. We identified 113 patients with functional dystonia and 125 with idiopathic dystonia. Sudden onset of dystonia, evidence of fixed dystonia, and acute peripheral trauma before dystonia onset were more frequent in the functional dystonia group. No study variable alone achieved satisfactory sensitivity and specificity, whereas a combination of variables yielded 85% sensitivity and 98% specificity. A diagnostic algorithm was developed to reduce the risk of misclassifying functional dystonia. The findings of Study 1 extend the current diagnostic approach to functional dystonia by showing that clinical information about symptom onset, fixed dystonia, and history of peripheral trauma may provide key clues in the diagnosis of functional dystonia. Study 2 was designed to provide practical guidance for clinicians in confirming or refuting suspected cervical dystonia, which is the most frequent type of dystonia. For this reason, participants of Study 2 were video-recorded according to a standardized protocol to assess 6 main clinical features possibly contributing to cervical dystonia diagnosis: presence of repetitive, patterned head/neck movements/postures inducing head/neck deviation from neutral position (item 1); sensory trick (item 2); and red flags related to conditions mimicking dystonia that should be absent in dystonia (items 3 to 6). Inter/intra-rater agreement among three independent raters was assessed by k statistics. To estimate sensitivity and specificity, the gold standard was cervical dystonia diagnosis reviewed at each site by independent senior neurologists. The validation sample included 43 idiopathic cervical dystonia patients and 21 control subjects. The best combination of sensitivity and specificity was observed considering all the items except for an item related to capability to voluntarily suppress spasms (sensitivity: 96.1%; specificity: 81%). The findings of Study 2 show that an accurate diagnosis of cervical dystonia can be achieved if, in addition to the core motor features, we also consider some clinical features related to dystonia mimics that should be absent in dystonia. In conclusion, this work sheds more light on the complex topic of the diagnosis of dystonia. Indeed, the algorithms proposed in Study 1 and Study 2 provide a helpful tool for clinicians in their practice

Pathophysiology and Treatment of Functional Paralysis: Insight from Transcranial Magnetic Stimulation

Functional paralysis (FP) or limb weakness is a common presentation of functional movement disorders (FMD), accounting for 18.1% of the clinical manifestations of FMD. The pathophysiology of FP is not known, but imaging studies have identified changes in structural and functional connectivity in multiple brain networks. It has been proposed that noninvasive brain stimulation techniques may be used to understand the pathophysiology of FP and may represent a possible therapeutic option. In this paper, we reviewed transcranial magnetic stimulation studies on functional paralysis, focusing on their pathophysiological and therapeutical implications. Overall, there is general agreement on the integrity of corticospinal pathways in FP, while conflicting results have been found about the net excitability of the primary motor cortex and its excitatory/inhibitory circuitry in resting conditions. The possible involvement of spinal cord circuits remains an under-investigated area. Repetitive transcranial magnetic stimulation appears to have a potential role as a safe and viable option for the treatment of functional paralysis, but more studies are needed to investigate optimal stimulation parameters and clarify its role in the context of other therapeutical options

evaluation of virtual learning environment for the professional training in public administration

In this paper, we describe a framework for the evaluation of a virtual learning environment in the Public Administration context. We describe the question of e-learning education of the Italian Public Administration employees and we analyse the characteristics of these learners [11, 13, 9]. These adults do not belong to the Internet Generation but they have to use the new educational tools, with the problems that this implies [9, 10, 15]. Citizens expect transparency and services personalization, efficiency and quality by the Public Administration. The Public Administration began this modernization process aimed at the improvement of the administrative action. The aim is to meet the needs of citizens that live in a complex society. This entails a re-examination of the role and the logic of work that find in the employees a master key for their success [6]. Therefore the most important element for this modernization process and for the reformation of the administrative action is the education of the employees [12, 14]. The European Council invited the member States to adopt the methodologies of e-learning for the education of their staff [4, 5]. In the last years a large number of employees have received training with the methodologies and the instruments of on-line education. The European Public Administrations had adopted on a large scale the e-learning for the education of their employees because this is a modality of in service-training that removes space and time bonds. Moreover this allows the utilisation of new educational techniques. The learning policies adopted by the governments highlight the importance of education in adulthood to be competitive in the knowledge society [4]. This type of education is oriented to provide and to develop the ability that can be utilised in a professional field, not to make up for knowledge opportunities missed at the time of compulsory school education. It is essential to provide the employees-learners a good quality learning object and Virtual Learning Environment [1, 2, 3]. For these reasons we had worked out a framework to evaluate the quality and the pedagogical efficacy of the Virtual Learning Environment (VLE) from the point of view of lifelong learning. The evaluation offers feedback to developers, tutors, teachers and the other involved people, and it is an important part for the guarantee of quality [7]. We are interested in finding general principles that are useful in the planning of the learning environment for the Public Administration employees. We describe the pedagogical implications of the adoption of e-learning in adult education, the reasons for its broad use in Public Administration. The virtual environment is a social space, and in this system a set of people (students, tutors, teachers, administration assistant, etc) interact, with different roles and needs. For this reason the evaluation of an e-learning environment embraces the evaluation of the process of delivery, the maintenance and the people involved [8]. The evaluation instruments could be created in order to estimate the quality expected, looked for and reached. For these reasons it is necessary to detect indicators able to find the minimum criteria of quality [3]. In a Virtual Learning Environment there are different elements that can be considered in order to evaluate the quality of the learning system, we have considered these: â?¢ The quality of communication system. â?¢ The quality of support services and the didactic staff. â?¢ The quality of administrative services. â?¢ The quality of learning objects. We also analyze the learnersâ?? needs regarding on-line education. The aim of this study was to find a learning environment suitable for Public Administration employees. References: [1] CNIPA (2007). I Quaderni - Vademecum per la realizzazione di progetti formativi in modalita e-learning nelle pubbliche amministrazioni, N°32, aprile 2007. [2] CNIPA (2004). Vademecum per la realizzazione di progetti formativi in modalita eLearning nelle PA, I Quaderni, n. 2. Retrieved December 14th, 2007 from: http://www.cnipa.gov.it/site/_contentfiles/01377500/1377508_cnipa_quaderno_2.pdf . [3] CNIPA (2004). Linee guida per i progetti formativi in modalita eLearning nelle PA, I Quaderni, n. 7. Retrieved December 14th, 2007 from: http://www.cnipa.gov.it/site/_contentfiles/01378400/1378474_I%20QUADERNI%20n7.qxd.pdf [4] European Council (2000). Lisbon European Council 23 and 24 March 2000 â?? Presidency Conclusions. Retrieved December 14th, 2007 from http://www.europarl.europa.eu/summits/lis1_en.htm. [5] European Council (2002). Presidency conclusions â?? Barcelona European Council 15 and 16 March 2002. Retrieved December 14th, 2007 from http://www.consilium.europa.eu/ueDocs/cms_Data/docs/pressData/en/ec/71025.pdf. [6] Formez (2006). Scenari e tendenze della formazione pubblica, Quaderni Formez N. 45. Roma, Formez Ufficio Stampa ed Editoria. [7] Joint Committee on Standards for Educational Evaluation (1994). The program evaluation standards. Thousand Oaks, Sage. [8] Khan, B.H. (2004). E-learning: progettazione e gestione. Trento, Erickson. [9] Knowles, M. (1970). The Modern Practice of Adult Education: Andragogy versus Pedagogy. New York, Association press. [10] Knowles, M. (1990). The Adult Learner: a neglected species. 4. ed. Houston, Gulf Publishing. [11] Liscia, R. (a cura di) (2006). E-learning in Italia. Una strategia per lâ??innovazione. Milano, Apogeo. [12] M.G. Mereu (Ed.), (2000) La rilevazione dei fabbisogni professionali e formativi nelle Regioni italiane, Isfol, Strumenti e Ricerche, Milano , Franco Angeli [13] Ministero per lâ??Innovazione e le Tecnologie (2002). Linee guida del Governo per lo sviluppo della Societa dellâ??Informazione. Retrieved December 14th, 2007 from http://www.interlex.it/testi/pdf/lineeguida.pdf. [14] MIPA. (2004). Programmare e valutare la formazione, una guida per le amministrazioni pubbliche. Milano, Lattanzio [15] Tough, A.M. (1979). The adult's learning projects. 2. ed. Austin, Learning Concepts

Olfactory Function as a Potential Predictor of Cognitive Impairment in Men and Women

Background: Different previous studies indicated olfactory function as a predictor of several types of cognitive impairment, in particular related to neurodegenerative disease. However, scanty data are available on the role of odor threshold (OT), odor discrimination (OD), and odor identification (OI) as a predictor of cognitive impairment. The aim of this study was to evaluate potential correlations between each factor of the olfactory function versus each specific cognitive domain of the Montreal Cognitive Assessment (MoCA) test on healthy subjects in relation to gender and age. Methods: Sniffin’ Sticks and MoCA tests were used to determine olfactory function and cognitive abilities, respectively. Results: In men, significant correlations were found in OT versus language index score and OI versus language and executive index score, while in women, OD and OI were correlated to visuospatial index score. Conclusions: Our data suggested that olfactory function (OT, OD, and OI) may be considered a predictor for cognitive impairment in relation to gender and age

Qualitative smell/taste disorders as sequelae of acute COVID-19

Background Qualitative smell/taste disorders (such as phantosmia, parosmia, phantogeusia, and parageusia) have not yet been fully characterized in patients who had COVID-19, whereas quantitative disturbances (i.e., reduction/loss of smell/taste) have been widely investigated. Objective To simultaneously assess the presence of both quantitative and qualitative smell/taste dysfunctions in patients who suffered from COVID-19. Methods We enrolled 17 consecutive patients who suffered from COVID-19 over the last 6 months and 21 healthy controls, matched for sex and age. After a negative nasopharyngeal swab, the Sniffin’ Sticks Test and the Taste Strips were used to assess olfactory and taste function, respectively. At the same time, the presence of phantosmia, parosmia, phantogeusia, and parageusia was investigated with a standardized questionnaire. Results Qualitative disturbances of smell and/or taste were found in 6/17 (35.3%) patients. Phantosmia was reported in 2/17 (11.8%) patients and parosmia in 4/17 (23.5%). There were no significant differences in smell test scores between patients who reported phantosmia and/or parosmia and patients who did not. Phantogeusia was described in 3/17 (17.6%) patients, and parageusia was identified in 4/17 (23.5%) patients. All tested patients were normogeusic. Conclusion Around one-third of patients who recover from COVID-19 may have persistent qualitative dysfunction in smell/taste domains. Detection of phantogeusia in long-term COVID-19 patients represents a further novel finding. Further investigation is needed to better characterize the pathophysiology of phantosmia, parosmia, phantogeusia, and parageusia in patients who had COVID-19

Frequency and Determinants of Olfactory Hallucinations in Parkinson’s Disease Patients

Background: Olfactory dysfunctions and hallucinations are considered common nonmotor symptoms in Parkinson’s disease (PD). Visual and auditory hallucinations are well-known; however, olfactory hallucinations (OHs) are not fully investigated. The aim of this study was to evaluate OHs in PD patients, and their correlation to motor impairment, cognitive abilities, visual and auditory hallucinations, and olfactory and gustatory function. Methods: A sample of 273 patients was enrolled: 141 PD patients (mean age SD: 70.1 9.5 years) and 132 healthy controls (mean age SD: 69.4 9.6 years). In all patients, the following parameters were evaluated: motor symptoms (UPDRSIII), olfactory function, cognitive abilities, and occurrence of OH, gustatory hallucinations (GHs), and visual/auditory hallucinations. Results: OHs were found only in PD patients with a percentage of 11.3%. Among PD patients with OHs, 2.8% also presented GHs. High significant frequencies of females, the presence of visual/auditory hallucinations, and a high mean UPDRS-III score were found in patients with OHs related to patients without them. Binary logistic regression evidenced the presence of visual/auditory hallucinations and sex as main variables predicting the presence of OHs. Conclusions: Our data indicated that OHs occur frequently in PD patients, especially in women, and often concomitant with visual and auditory hallucinations, without any association with olfactory impairment

Combined measure of salivary alpha-synuclein species as diagnostic biomarker for Parkinson's disease

Parkinson's disease (PD) diagnosis is still vulnerable to bias, and a definitive diagnosis often relies on post-mortem neuropathological diagnosis. In this regard, alpha-synuclein (αsyn)-specific in vivo biomarkers remain a critical unmet need, based on its relevance in the neuropathology. Specifically, content changes in αsyn species such as total (tot-αsyn), oligomeric (o-αsyn), and phosphorylated (p-αsyn) within the cerebrospinal fluid (CSF) and peripheral fluids (i.e., blood and saliva) have been proposed as PD biomarkers possibly reflecting the neuropathological outcome. Here, we measured the p-αsyn levels in the saliva from 15 PD patients along with tot-αsyn, o-αsyn and their ratios, and compared the results with those from 23 healthy subjects (HS), matched per age and sex. We also calculated the optimal cutoff values for different αsyn species to provide information about their capability to discriminate PD from HS. We found that p-αsyn was the most abundant alpha-synuclein species in the saliva. While p-αsyn concentration did not differ between PD and HS when adjusted for total salivary proteins, the ratio p-αsyn/tot-αsyn was largely lower in PD patients than in HS. Moreover, the concentration of o-αsyn was increased in the saliva of PD patients, and tot-αsyn did not differ between PD and HS. The ROC curves indicated that no single αsyn form or ratio could provide an accurate diagnosis of PD. On the other hand, the ratio of different items, namely p-αsyn/tot-αsyn and o-αsyn, yielded more satisfactory diagnostic accuracy, suggesting that the combined measure of different species in the saliva may show more promises as a diagnostic means for PD

Exploring the Association between Cathepsin B and Parkinson’s Disease

Objective: The aim of this study is to investigate the association between Cathepsin B and Parkinson’s Disease (PD), with a particular focus on determining the role of N-acetylaspartate as a potential mediator. Methods: We used summary-level data from Genome-Wide Association Studies (GWAS) for a two-sample Mendelian randomization (MR) analysis, exploring the association between Cathepsin B (3301 cases) and PD (4681 cases). A sequential two-step MR approach was applied (8148 cases) to study the role of N-acetylaspartate. Results: The MR analysis yielded that genetically predicted elevated Cathepsin B levels correlated with a reduced risk of developing PD (p = 0.0133, OR: 0.9171, 95% CI: 0.8563–0.9821). On the other hand, the analysis provided insufficient evidence to determine that PD affected Cathepsin B levels (p = 0.8567, OR: 1.0035, 95% CI: 0.9666–1.0418). The estimated effect of N-acetylaspartate in this process was 7.52% (95% CI = −3.65% to 18.69%). Conclusions: This study suggested that elevated Cathepsin B levels decreased the risk of developing PD, with the mediation effect of N-acetylaspartate. Further research is needed to better understand this relationship