Quantitative Tests des statischen Gleichgewichts in der Prodromalphase des Parkinson-Syndroms

Das idiopathische Parkinson Syndrom (IPS) entwickelt sich bereits Jahrzehnte bevor eine klinische Diagnose möglich ist. Diese prodromale Phase stellt den Interessenschwerpunkt intensiver Forschung dar, die langfristig ermöglichen soll, anhand von Markern bzw. Parametern Hochrisikopersonen für ein IPS (HRP) bzw. diejenigen, die ein IPS entwickeln werden, von gesunden Kontrollen zu unterscheiden. In dieser prodromalen Phase finden sich u.a. motorische „Frühzeichen“, welche dem IPS vorangehen. Diese Veränderungen können mittels inertialer Sensorsysteme sensitiv, reliabel und valide erfasst werden und bieten als quantitative Messsysteme die Möglichkeit, subtile Veränderungen zu objektivieren. Die vorliegende Arbeit stellt die Anwendung zweier - mittels inertialer Sensoren erhobener - quantitativer Tests des statischen Gleichgewichts in der Prodromalphase des IPS vor. Dafür wurde das statische Gleichgewicht einmal an der selbstgewählten Mitte im Rahmen der TREND-Studie, sowie an der selbstgewählten Grenze der Stabilität in der PMPP-Studie untersucht. Des Weiteren beschreibt diese Arbeit deskriptiv die Ergebnisse der statischen Gleichgewichtstestung in der selbstgewählten Mitte von 7 Konvertierern bis zu 4 Jahre vor der klinischen Diagnose des IPS. Im Test des statischen Gleichgewichts an der selbstgewählten Mitte zeigten sich Unterschiede zwischen Probanden mit 0, 1, 2 Prodromalmarkern (PM) und IPS Patienten in den Parametern des Schwingungs- und Ausgleichverhaltens (Sway) Fläche und mittlere Leistungsdichte (MPF). Personen mit 3 PM unterschieden sich nicht signifikant von den IPS Patienten. Explorative Analysen zeigten Trends zur Unterscheidung der 3 PM Gruppe zu den Personen mit 0, 1 und tlw. 2 PM auf. Daraus ist zu folgern, dass die Testung des statischen Gleichgewichts an der selbstgewählten Mitte das Potential birgt, anhand einer Auswahl an Parametern, eine Unterscheidung zwischen Hochrisikopersonen für das IPS (HRP) und gesunden Kontrollen langfristig zu ermöglichen. Die deskriptiven Analysen der Sway Daten der 7 Konvertierer im Vergleich zu IPS Patienten mit kürzerem und längerem Krankheitsverlauf deuten eine lineare Veränderung der Parameter Fläche, Geschwindigkeit und MPF von prodromalem in Richtung klinisch evidentes IPS an. Die Parameter Beschleunigung und Jerk zeigen einen U-förmigen Verlauf an. Daraus ist zu folgern, dass eine Messung des Verlaufs der Erkrankung, anhand einer Auswahl von Sway Parametern, möglich ist. Weitere Untersuchungen und größere Stichproben sind notwendig, um nähere Aussagen über den Verlauf und die Bedeutung einzelner Parameter treffen zu können. Der Test der Funktionellen Reichweite (FR) unterscheidet für die erreichte Distanz zwischen gesunden Kontrollen und IPS Patienten. Werden die dabei erhobenen Sway Parameter im Sinne eines instrumentierten FR (iFR) als Test des statischen Gleichgewichts an den Grenzen der Stabilität erfasst, so unterscheiden sich Kontrollen und IPS Patienten in der Beschleunigung, sowohl in anterior-posteriore (AP) als auch mediolaterale (ML) Richtung. Werden diese und in Vorab-Analysen als bedeutsam ermittelten Werte in ein Modell zur Unterscheidung zwischen den Kontrollen und HRP herangezogen, so ergibt sich eine AUC von 0.77 mit einer Sensitivität von 77% und Spezifität von 85%. Daraus ist zu folgern, dass der iFR das Potential besitzt – zusammen mit weiteren Assessments – zur Unterscheidung von HRP und gesunden Kontrollen beizutragen. Unseres Wissens stellt dies die erste Arbeit über den Verlauf der Sway Parameter in der prodromalen Phase des IPS von 7 Konvertierern sowie die erstmalige Anwendung eines instrumentierten Tests der Funktionellen Reichweite dar. Die Ergebnisse zeigen, dass fordernde Gleichgewichtsaufgaben das Potential bergen, mittels inertialer Sensoren HRP von Kontrollen zu unterscheiden sowie Unterschiede detektieren zu können. Bereits jetzt sind mit dem iFR eine Unterscheidung mit mittlerer Sensitivität und Spezifität möglich. Die Integration, dieser mit weiteren Tests der Motorik sowie in Kombination mit weiteren PM und Risikomarkern (RM) zu einem Panel an Untersuchungen, bietet die Chance, HRP früher zu erkennen, longitudinal Veränderungen abzubilden und auf ihre Konsistenz zu überprüfen, sowie letztendlich Kohorten für die Testung von neuromodulatorischen / -protektiven Substanzen zu generieren. Schlussendlich stellt diese Arbeit den Ausgangspunkt für weitere quantitative Untersuchungen des statischen Gleichgewichts dar. Weitere, insbesondere longitudinale Untersuchungen sind nötig, um diese Ergebnisse zu replizieren und ihre Bedeutung im Rahmen der prodromalen Phase des IPS abzubilden.

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 standarized ST and dual tasks (DT) as fast as possible for one minute 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

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 (r(2) = 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

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

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

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.</div

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

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.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.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.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

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