Thyroidal Angiotensin-Converting Enzyme 2 Protein Expression and Thyroid Function Tests in Patients with COVID-19: Results from a Retrospective Case Series and a Prospective Cohort Study.

Background: Infection with SARS-CoV-2 has initially been known as a respiratory disease but in the course of the pandemic the understanding has emerged that severity is owing to fatal inflammatory responses apart from lung injury. In this context, endocrine disorders such as thyroiditis as well as pituitary dysfunction in addition to nonthyroidal illness syndrome have been described. Furthermore, angiotensin-converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, has been detected in most endocrine tissues, including the thyroid gland. Objective: To evaluate histopathologic changes and compare thyroidal ACE2 protein expression in thyroid tissue from patients who died from severe COVID-19 with thyroid tissue from patients without SARS-CoV-2 infection in a retrospective case series. Furthermore, to assess and compare alterations in thyroid function tests (TFTs) between patients with or without SARS-CoV-2 infection as well as association of TFTs with the severity of the disease in a prospective cohort study. Methods: Thyroid tissue of deceased COVID-19 patients (n = 23) was analyzed for histopathology and ACE2 expression by immunohistochemical staining. A total of 153 patients with confirmed SARS-CoV-2 were evaluated regarding TFTs and divided into a severe (intubation, intensive care treatment) and an intermediate group. Results: Thyroidal ACE2 expression was detected in 87% of the deceased COVID-19 patients. Normal thyroid tissue from patients without SARS-CoV-2 infection showed no ACE2 protein expression. Half of the severely ill COVID-19 patients had low free triiodothyronine (fT3) levels. Combination of low fT3 and thyrotropin (TSH) was associated significantly with deadly disease. Conclusion: The high percentage of positive ACE2 immunostaining in deceased patients compared with normal thyroid tissue of patients without SARS-CoV-2 infection suggests involvement of the thyroid in COVID-19, although further research will have to show the pathogenic role of thyroidal ACE2 in COVID-19. Abnormal fT3 and a TSH of ≤0.5 mU/L were associated with a fatal outcome in our severely ill SARS-CoV-2 patient cohort. Therefore, assessment of TFTs is crucial in the treatment of severely ill COVID-19 patients. Trial Registration: COVID-19 Registry of the LMU University Hospital Munich (CORKUM), WHO trial ID DRKS00021225.

Diminished Short- and Long-Term Antibody Response after SARS-CoV-2 Vaccination in Hemodialysis Patients.

Short-term studies have shown an attenuated immune response in hemodialysis patients after COVID-19-vaccination. The present study examines how antibody response is maintained after vaccination against SARS-CoV-2 in a large population of hemodialysis patients from six outpatient dialysis centers. We retrospectively assessed serum antibody levels against SARS-CoV-2 spike protein and nucleocapsid protein (electrochemiluminescence immunoassays, Roche Diagnostics) after COVID-19-vaccination in 298 hemodialysis and 103 non-dialysis patients (controls), comparing early and late antibody response. Compared to a non-dialysis cohort hemodialysis patients showed a favorable but profoundly lower early antibody response, which decreased substantially during follow-up measurement (median 6 months after vaccination). Significantly more hemodialysis patients had anti-SARS-CoV-2-S antibody titers below 100 U/mL (p < 0.001), which increased during follow-up from 23% to 45% but remained low in the control group (3% vs. 7%). In multivariate analysis, previous COVID-19 infections (p < 0.001) and female gender (p < 0.05) were significantly associated with higher early as well as late antibody vaccine response in hemodialysis patients, while there was a significant inverse correlation between patient age and systemic immunosuppression (p < 0.001). The early and late antibody responses were significantly higher in patients receiving vaccination after a SARS-CoV-2 infection compared to uninfected patients in both groups (p < 0.05). We also note that a higher titer after complete immunization positively affected late antibody response. The observation, that hemodialysis patients showed a significantly stronger decline of SARS-CoV-2 vaccination antibody titers within 6 months, compared to controls, supports the need for booster vaccinations to foster a stronger and more persistent antibody response.

Genomic epidemiology reveals multiple introductions of SARS-CoV-2 followed by community and nosocomial spread, Germany, February to May 2020.

BackgroundIn the SARS-CoV-2 pandemic, viral genomes are available at unprecedented speed, but spatio-temporal bias in genome sequence sampling precludes phylogeographical inference without additional contextual data.AimWe applied genomic epidemiology to trace SARS-CoV-2 spread on an international, national and local level, to illustrate how transmission chains can be resolved to the level of a single event and single person using integrated sequence data and spatio-temporal metadata.MethodsWe investigated 289 COVID-19 cases at a university hospital in Munich, Germany, between 29 February and 27 May 2020. Using the ARTIC protocol, we obtained near full-length viral genomes from 174 SARS-CoV-2-positive respiratory samples. Phylogenetic analyses using the Auspice software were employed in combination with anamnestic reporting of travel history, interpersonal interactions and perceived high-risk exposures among patients and healthcare workers to characterise cluster outbreaks and establish likely scenarios and timelines of transmission.ResultsWe identified multiple independent introductions in the Munich Metropolitan Region during the first weeks of the first pandemic wave, mainly by travellers returning from popular skiing areas in the Alps. In these early weeks, the rate of presumable hospital-acquired infections among patients and in particular healthcare workers was high (9.6% and 54%, respectively) and we illustrated how transmission chains can be dissected at high resolution combining virus sequences and spatio-temporal networks of human interactions.ConclusionsEarly spread of SARS-CoV-2 in Europe was catalysed by superspreading events and regional hotspots during the winter holiday season. Genomic epidemiology can be employed to trace viral spread and inform effective containment strategies.

Antibody response to mRNA SARS-CoV-2 vaccines in haemodialysis patients.

BACKGROUND: Some studies have shown an attenuated immune response in haemodialysis patients after vaccination. The present study examines the humoral response after mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a large population of haemodialysis patients from different outpatient dialysis centres. METHODS: We retrospectively assessed antibodies against SARS-CoV-2 spike protein and nucleocapsid protein (chemiluminescence immunoassays, Roche diagnostics) 3-6 weeks after the second mRNA vaccine dose in 179 maintenance haemodialysis and 70 non-dialysis patients (control cohort). Differences in anti-SARS-CoV-2 spike protein titers were statistically analysed with respect to patient-relevant factors, including age, gender, previous coronavirus disease 2019 (COVID-19) infection, systemic immunosuppressive therapy and time on dialysis. RESULTS: We found a favourable, but profoundly lower SARS-CoV-2 spike protein antibody response in comparison with a non-dialysis cohort (median 253.5 versus 1756 U/mL, P < 0.001). In multivariate analysis, previous COVID-19 infection (P < 0.001) and female gender were associated with a significantly higher vaccine response (P = 0.006) in haemodialysis patients, while there was a significant inverse correlation with increasing patient age and systemic immunosuppression (P < 0.001). There was no statistically significant correlation between the antibody titer and time on dialysis. Immune response in haemodialysis patients with a previous COVID-19 infection led to substantially higher antibody titers that were equal to those of vaccinated non-dialysis individuals with previous infection. CONCLUSION: We strongly argue in favour of regular antibody testing after COVID-19 vaccination in haemodialysis patients. Further studies should elucidate the utility of booster vaccinations to foster a stronger and persistent antibody response.

PREOPERATIVE ANALYSIS OF RADIOGRAPHIC FINDINGS IN 516 PATIENTS WITH HALLUX VALGUS DEFORMITY.

OBJECTIVE: This is a descriptive study to report our method of operative correction for patients with hallux valgus deformities. METHODS: From 2006 to 2012, 516 consecutive patients (601 feet) with hallux valgus deformities were treated surgically in our department after conservative treatments were exhausted. The hallux valgus angle, intermetatarsal angle, distal metatarsal articular angle, and degree of osteoarthritis in the first metatarsophalangeal joint were measured on preoperative plain radiographs of the weight-bearing forefoot. RESULTS: Young patients with severe intermetatarsal deviation received a combined proximal and distal osteotomy of the first metatarsal (n = 21). Patients with low intermetatarsal deviation received a distal metatarsal chevron osteotomy (n = 196), whereas patients with severe intermetatarsal deviation and less flexible deformities without osteoarthritis received a basal metatarsal osteotomy with a distal soft tissue procedure (n = 173). Elderly active patients with osteoarthritis in the first metatarsophalangeal joint received an arthrodesis (n = 100) or resection arthroplasty (n = 58). CONCLUSION: Determining a few simple angles on plain radiographs of the weight-bearing forefoot in combination with the age and level of activity of patients can help simplify the operative correction method by using the schema we developed. Level of evidence IV, case series.

OBJETIVO: Este é um estudo descritivo para relatar nosso método de correção cirúrgica para pacientes com deformidades de hálux valgo. MÉTODOS: De 2006 a 2012, 516 pacientes consecutivos (601 pés) com deformidade de hálux valgo foram tratados cirurgicamente em nosso departamento, depois que os tratamentos conservadores foram esgotados. O ângulo do hálux valgo, o ângulo intermetatarsal, o ângulo articular metatarsal distal e o grau de osteoartrite da primeira articulação metatarsofalângica foram medidos em radiografias pré-operatórias simples do antepé com apoio de peso. RESULTADOS: Os pacientes jovens com desvio intermetatarsal grave foram submetidos à combinação de osteotomia distal e proximal do primeiro metatarso (n = 21). Os pacientes com desvio intermetatarsal menor foram submetidos a osteotomia de Chevron no metatarso distal (n = 196), enquanto que os pacientes com desvio intermetatarsal grave e deformidades menos flexíveis e sem osteoartrite foram submetidos a osteotomia da base do metatarso com um procedimento distal no tecido mole (n = 173). Nos pacientes idosos ativos com osteoartrite na primeira articulação metatarsofalângica realizou-se artrodese (n = 100) ou artroplastia de ressecção (n = 58). CONCLUSÃO: Determinar alguns ângulos com radiografias simples do antepé com apoio de peso em combinação com idade e nível de atividade dos pacientes pode ajudar e simplificar o método de correção cirúrgica, usando o esquema que desenvolvemos. Nível de Evidência IV, Série de casos.

Preoperative analysis of radiographic findings in 516 patients with hallux valgus deformity / Análise pré-operatória de achados radiográficos em 516 pacientes com deformidade de hallux valgus

ABSTRACT Objective: This is a descriptive study to report our method of operative correction for patients with hallux valgus deformities. Methods: From 2006 to 2012, 516 consecutive patients (601 feet) with hallux valgus deformities were treated surgically in our department after conservative treatments were exhausted. The hallux valgus angle, intermetatarsal angle, distal metatarsal articular angle, and degree of osteoarthritis in the first metatarsophalangeal joint were measured on preoperative plain radiographs of the weight-bearing forefoot. Results: Young patients with severe intermetatarsal deviation received a combined proximal and distal osteotomy of the first metatarsal (n = 21). Patients with low intermetatarsal deviation received a distal metatarsal chevron osteotomy (n = 196), whereas patients with severe intermetatarsal deviation and less flexible deformities without osteoarthritis received a basal metatarsal osteotomy with a distal soft tissue procedure (n = 173). Elderly active patients with osteoarthritis in the first metatarsophalangeal joint received an arthrodesis (n = 100) or resection arthroplasty (n = 58). Conclusion: Determining a few simple angles on plain radiographs of the weight-bearing forefoot in combination with the age and level of activity of patients can help simplify the operative correction method by using the schema we developed. Level of evidence IV, case series.

RESUMO Objetivo: Este é um estudo descritivo para relatar nosso método de correção cirúrgica para pacientes com deformidades de hálux valgo. Métodos: De 2006 a 2012, 516 pacientes consecutivos (601 pés) com deformidade de hálux valgo foram tratados cirurgicamente em nosso departamento, depois que os tratamentos conservadores foram esgotados. O ângulo do hálux valgo, o ângulo intermetatarsal, o ângulo articular metatarsal distal e o grau de osteoartrite da primeira articulação metatarsofalângica foram medidos em radiografias pré-operatórias simples do antepé com apoio de peso. Resultados: Os pacientes jovens com desvio intermetatarsal grave foram submetidos à combinação de osteotomia distal e proximal do primeiro metatarso (n = 21). Os pacientes com desvio intermetatarsal menor foram submetidos a osteotomia de Chevron no metatarso distal (n = 196), enquanto que os pacientes com desvio intermetatarsal grave e deformidades menos flexíveis e sem osteoartrite foram submetidos a osteotomia da base do metatarso com um procedimento distal no tecido mole (n = 173). Nos pacientes idosos ativos com osteoartrite na primeira articulação metatarsofalângica realizou-se artrodese (n = 100) ou artroplastia de ressecção (n = 58). Conclusão: Determinar alguns ângulos com radiografias simples do antepé com apoio de peso em combinação com idade e nível de atividade dos pacientes pode ajudar e simplificar o método de correção cirúrgica, usando o esquema que desenvolvemos. Nível de Evidência IV, Série de casos.

Gait Is Associated with Cognitive Flexibility: A Dual-Tasking Study in Healthy Older People.

Objectives: To analyze which gait parameters are primarily influenced by cognitive flexibility, and whether such an effect depends on the walking condition used. Design: Cross-sectional analysis. Setting: Tübingen evaluation of Risk factors for Early detection of Neurodegenerative Disorders. Participants: A total of 661 non-demented individuals (49-80 years). Measurements: A gait assessment with four conditions was performed: a 20 m walk at convenient speed (C), at fast speed (F), at fast speed while checking boxes (FB), and while subtracting serial 7s (FS). Seven gait parameters from a wearable sensor-unit (McRoberts, Netherlands) were compared with delta Trail-Making-Test (dTMT) values, which is a measure of cognitive flexibility. Walking strategies of good and poor dTMT performers were compared by evaluating the patterns of gait parameters across conditions. Results: Five parameters correlated significantly with the dTMT in the FS condition, two parameters in the F and FB condition, and none in the C condition. Overall correlations were relatively weak. Gait speed was the gait parameter that most strongly correlated with the dTMT (r2 = 7.4%). In good, but not poor, dTMT performers differences between FB and FS were significantly different in variability-associated gait parameters. Conclusion: Older individuals need cognitive flexibility to perform difficult walking conditions. This association is best seen in gait speed. New and particularly relevant for recognition and training of deficits is that older individuals with poor cognitive flexibility have obviously fewer resources to adapt to challenging walking conditions. Our findings partially explain gait deficits in older adults with poor cognitive flexibility.

Evidence for a Selectively Regulated Prioritization Shift Depending on Walking Situations in Older Adults.

Background: Older adults have increased risks of balance issues and falls when walking and performing turns in daily situations. Changes of prioritization during different walking situations associated with dual tasking may contribute to these deficits. The objective of this study was therefore to investigate whether older adults demonstrate changes of prioritization during different walking paths. Methods: In total, 1,054 subjects with an age range from 50 to 83 years were selected from the first follow-up visit of the TREND (Tuebinger evaluation of Risk factors for Early detection of Neurodegenerative Disorders) study. They were classified according to their performance on the Trail Making Test (TMT) into good and poor TMT performers (based on recent results showing that cognitive flexibility affects prioritization strategies during straight walking). Absolute dual-task performance and relative dual-task costs (DTC, relative performance under dual-task conditions compared with single-task conditions) were assessed in two paradigms: walking while subtracting serial 7 s and walking while checking boxes on a clipboard. Both tasks were performed on straight and curved paths. Results: Overall, the poor TMT performers group performed worse in all single and dual tasks. Interestingly, the relative change in performance measured by dual-task costs differed in the groups between the two walking paths. On straight paths, poor TMT performers had a similar DTC of walking to that of good performers (p = 0.10) but had a significantly lower DTC of subtracting (p = 0.02). On curved paths, poor performers had a similar DTC of subtracting (p = 0.10), but their DTC of walking was significantly higher (p < 0.0001). Conclusion: Given that walking on curved paths is considered more difficult than that on straight paths and that the serial subtracting dual task is more difficult than the box checking dual task, this study in older adults provides evidence for the existence of a (walking) situation-dependent change of prioritization. If confirmed in other studies, situation-dependent change of prioritization should be included as a potential factor contributing to gait and balance impairments, and increased fall risk in older adults.

Associations between Early Markers of Parkinson's Disease and Sarcopenia.

Introduction: Sarcopenia and Parkinson's disease (PD) are both common age-related syndromes, and there is preliminary evidence that the probability of the co-occurrence of these syndromes within one individual is higher than expected. However, it is unclear to date whether one of the syndromes induces the other, or whether there may be common underlying causes. This pilot study thus aimed at investigating the association of the features of increased risk for PD with early stage sarcopenia (ESS). Method: Two hundred and fifty-five community-dwelling individuals were recruited from the Tübinger evaluation of Risk factors for Early detection of NeuroDegeneration (TREND) study. The following features that are associated with an increased risk for future PD were evaluated: the motor part of the Unified PD Rating Scale (UPDRS-III), hyperechogenicity of the substantia nigra, prevalence of lifetime depression, hyposmia, REM sleep behavior disorder and the recently introduced probability score for prodromal PD. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People, which was adapted to this cohort of healthy adults. Multiple linear regression analysis was used to identify associations of PD-related features with ESS. Results: The UPDRS-III score was significantly associated with ESS. The result remained significant after the adjustment for age, gender and physical activity. No association was found between the other PD-related features and ESS. Conclusion: The significant association of the UPDRS-III score with ESS in this cohort might indicate a common and early pathway in both diseases and supports the existence of an "extended neurodegenerative overlap syndrome." Moreover, the potential of EES to serve as a prodromal marker of PD should be evaluated in future studies.

Dual Tasking for the Differentiation between Depression and Mild Cognitive Impairment.

Differentiation of mild cognitive impairment from depression in elderly adults is a clinically relevant issue which is not sufficiently solved. Gait and dual task (DT) parameters may have the potential to complement current diagnostic work-up, as both dementia and depression are associated with changes of gait and DT parameters. METHODS: Seven hundred and four participants of the TREND study (Tübinger evaluation of Risk factors for Early detection of NeuroDegeneration) aged 50-80 years were assessed using the Consortium to Establish a Registry for Alzheimer's Disease Plus test battery for testing cognition and Beck's Depression Inventory for evaluation of depression. Based on these results, four groups were defined: acute depressed (N = 53), cognitively mildly impaired (N = 97), acute depressed, and cognitively mildly impaired (N = 15), and controls (N = 536). Participants underwent a 20 m walk and checking boxes task under single (ST) and DT conditions. ST and DT performance and dual task costs (DTC) were calculated. Due to the typical age of increasing incidence of depressive and also cognitive symptoms, the 7th decade was calculated separately. RESULTS: ST speeds of gait and checking boxes, DT walking speed, and walking DTC were significantly different between groups. Healthy controls were the fastest in all paradigms and cognitively mildly impaired had higher DTC than depressed individuals. Additionally, we constructed a multivariate predictive model differentiating the groups on a single-subject level. CONCLUSION: DT parameters are simply and comfortably measureable, and DTC can easily be determined. The combination of these parameters allows a differentiation of depressed and cognitively mildly impaired elderly adults.

Quantitative Timed-Up-and-Go Parameters in Relation to Cognitive Parameters and Health-Related Quality of Life in Mild-to-Moderate Parkinson's Disease.

INTRODUCTION: The instrumented-Timed-Up-and-Go test (iTUG) provides detailed information about the following movement patterns: sit-to-walk (siwa), straight walking, turning and walk-to-sit (wasi). We were interested in the relative contributions of respective iTUG sub-phases to specific clinical deficits most relevant for daily life in Parkinson's disease (PD). More specifically, we investigated which condition-fast speed (FS) or convenient speed (CS)-differentiates best between mild- to moderate-stage PD patients and controls, which parameters of the iTUG sub-phases are significantly different between PD patients and controls, and how the iTUG parameters associate with cognitive parameters (with particular focus on cognitive flexibility and working memory) and Health-Related-Quality of Life (HRQoL). METHODS: Twenty-eight PD participants (65.1 ± 7.1 years, H&Y stage 1-3, medication OFF state) and 20 controls (66.1 ± 7.5 years) performed an iTUG (DynaPort®, McRoberts BV, The Netherlands) under CS and FS conditions. The PD Questionnaire 39 (PDQ-39) was employed to assess HRQoL. General cognitive and executive functions were assessed using the Montreal Cognitive Assessment and the Trail Making Test. RESULTS: The total iTUG duration and sub-phases durations under FS condition differentiated PD patients slightly better from controls, compared to the CS condition. The following sub-phases were responsible for the observed longer total duration PD patients needed to perform the iTUG: siwa, turn and wasi. None of the iTUG parameters correlated relevantly with general cognitive function. Turning duration and wasi maximum flexion velocity correlated strongest with executive function. Walking back duration correlated strongest with HRQoL. DISCUSSION: This study confirms that mild- to moderate-stage PD patients need more time to perform the iTUG than controls, and adds the following aspects to current literature: FS may be more powerful than CS to delineate subtle movement deficits in mild- to moderate-stage PD patients; correlation levels of intra-individual siwa and wasi parameters may be interesting surrogate markers for the level of automaticity of performed movements; and sub-phases and kinematic parameters of the iTUG may have the potential to reflect executive functioning and HRQoL aspects of PD patients.

Motor dual-tasking deficits predict falls in Parkinson's disease: A prospective study.

INTRODUCTION: Falls severely affect lives of Parkinson's disease (PD) patients. Cognitive impairment including dual-tasking deficits contribute to fall risk in PD. However, types of dual-tasking deficits preceding falls in PD are still unclear. METHODS: Walking velocities during box-checking and subtracting serial 7s were assessed twice a year in 40 PD patients over 2.8 ± 1.0 years. Fourteen patients reported a fall within this period (4 excluded fallers already reported falls at baseline). Their dual-task costs (DTC; mean ± standard deviation) 4.2 ± 2.2 months before the first fall were compared with 22 patients never reporting falls. ROC analyses and logistic regressions accounting for DTC, UPDRS-III and disease duration were used for faller classification and prediction. RESULTS: Only walking/box-checking predicted fallers. Fallers showed higher DTC for walking while box-checking, p = 0.029, but not for box-checking while walking, p = 0.178 (combined motor DTC, p = 0.022), than non-fallers. Combined motor DTC classified fallers and non-fallers (area under curve: 0.75; 95% confidence interval, CI: 0.60-0.91) with 71.4% sensitivity (95%CI: 41.9%-91.6%) and 77.3% specificity (54.6%-92.2%), and significantly predicted future fallers (p = 0.023). Here, 20.4%-points higher combined motor DTC (i.e. the mean difference between fallers and non-fallers) was associated with a 2.6 (1.1-6.0) times higher odds to be a future faller. CONCLUSION: Motor dual-tasking is a potentially valuable predictor of falls in PD, suggesting that avoiding dual task situations as well as specific motor dual-task training might help to prevent falls in PD. These findings and their therapeutic relevance need to be further validated in PD patients without fall history, in early PD stages, and with various motor-motor dual-task challenges.

Limited Effect of Dopaminergic Medication on Straight Walking and Turning in Early-to-Moderate Parkinson's Disease during Single and Dual Tasking.

BACKGROUND: In Parkinson's disease (PD), the effects of dopaminergic medication on straight walking and turning were mainly investigated under single tasking (ST) conditions. However, multitasking situations are considered more daily relevant. METHODS: Thirty-nine early-to-moderate PD patients performed the following standardized ST and dual tasks as fast as possible for 1 min during On- and Off-medication while wearing inertial sensors: straight walking and turning, checking boxes, and subtracting serial 7s. Quantitative gait parameters as well as velocity of the secondary tasks were analyzed. RESULTS: The following parameters improved significantly in On-medication during ST: gait velocity during straight walking (p = 0.03); step duration (p = 0.048) and peak velocity (p = 0.04) during turning; velocity of checking boxes during ST (p = 0.04) and DT (p = 0.04). Velocity of checking boxes was the only parameter that also improved during DT. CONCLUSION: These results suggest that dopaminergic medication does not relevantly influence straight walking and turning in early-to-moderate PD during DT.

Instrumented functional reach test differentiates individuals at high risk for Parkinson's disease from controls.

The functional reach (FR) test as a complex measure of balance including limits of stability has been proven to differentiate between patients with Parkinson's disease (PD) and controls (CO). Recently, it has been shown that the instrumentation of the FR (iFR) with a wearable sensor may increase this diagnostic accuracy. This cross-sectional study aimed at investigating whether the iFR has the potential to differentiate individuals with high risk for PD (HRPD) from CO, as the delineation of such individuals would allow for, e.g., early neuromodulation. Thirteen PD patients, 13 CO, and 31 HRPD were investigated. HRPD was defined by presence of an enlarged area of hyperechogenicity in the mesencephalon on transcranial sonography and either one motor sign or two risk and prodromal markers of PD. All participants were asked to reach with their right arm forward as far as possible and hold this position for 10 s. During this period, sway parameters were assessed with an accelerometer (Dynaport, McRoberts) worn at the lower back. Extracted parameters that differed significantly between PD patients and CO in our cohort [FR distance (shorter in PD), anterior-posterior and mediolateral acceleration (both lower in PD)] as well as JERK, which has been shown to differentiate HRPD from CO and PD in a previous study, were included in a model, which was then used to differentiate HRPD from CO. The model yielded an area under the curve of 0.77, with a specificity of 85%, and a sensitivity of 74%. These results suggest that the iFR can contribute to an assessment panel focusing on the definition of HRPD individuals.

Mild parkinsonian signs in the elderly--is there an association with PD? Crossectional findings in 992 individuals.

BACKGROUND: Mild parkinsonian signs (MPS) are common in the elderly population, and have been associated with vascular diseases, mild cognitive impairment and dementia; however their relation to Parkinson's disease (PD) is unclear. Hypothesizing that individuals with MPS may reflect a pre-stage of PD, i.e. a stage in which the nigrostriatal system is already affected although to a milder degree than at the time of PD diagnosis, aim of this study was to evaluate the similarities between MPS and PD. METHODS: The TREND study is a prospective cross-sectional cohort study in individuals >50 years with biennial assessments designed to identify markers for an earlier diagnosis of Parkinson's and Alzheimer's disease. For this substudy 992 individuals were included for analyses (892 controls, 73 MPS individuals, 27 PD patients). Parameters defining risk of PD (sex, age, positive family history), prodromal markers (hyposmia, REM sleep behavior disorder, depression and autonomic failure) as well as quantitative fine motor, axial motor and cognitive parameters were compared between the three cohorts. RESULTS: As expected, PD patients differed from controls with regard to 12 of 15 of the assessed parameters. MPS individuals differed significantly from controls in 12 of the PD-associated parameters, but differed from PD only in 5 parameters. CONCLUSION: This study shows that individuals with MPS share many prodromal and clinical markers of PD with PD patients, implying that either a common dynamic process or similar constitutional factors occur in MPS individuals and PD patients.

Emerging therapies for gait disability and balance impairment: promises and pitfalls.

Therapeutic management of gait and balance impairment during aging and neurodegeneration has long been a neglected topic. This has changed considerably during recent years, for several reasons: (1) an increasing recognition that gait and balance deficits are among the most relevant determinants of an impaired quality of life and increased mortality for affected individuals; (2) the arrival of new technology, which has allowed for new insights into the anatomy and functional (dis)integrity of gait and balance circuits; and (3) based in part on these improved insights, the development of new, more specific treatment strategies in the field of pharmacotherapy, deep brain surgery, and physiotherapy. The initial experience with these emerging treatments is encouraging, although much work remains to be done. The objective of this narrative review is to discuss several promising developments in the field of gait and balance treatment. We also address several pitfalls that can potentially hinder a fast and efficient continuation of this vital progress. Important issues that should be considered in future research include a clear differentiation between gait and balance as two distinctive targets for treatment and recognition of compensatory mechanisms as a separate target for therapeutic intervention.