The Role of Levodopa Challenge in Predicting the Outcome of Subthalamic Deep Brain Stimulation.

Background: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective and evidence-based treatment for idiopathic Parkinson's disease (iPD). A minority of patients does not sufficiently benefit from STN-DBS. Objective: The predictive validity of the levodopa challenge for individual patients is analyzed. Methods: Data from patients assessed with a preoperative Levodopa-test and a follow-up examination (mean ± standard deviation: 9.15 months ±3.39) from Kiel (n = 253), Berlin (n = 78) and Toronto (n = 98) were studied. Insufficient DBS outcome was defined as an overall UPDRS-III reduction <33% compared to UPDRS-III in med-off at baseline or alternatively if the minimal clinically important improvement of 5 points was not reached. Single UPDRS-items and sub-scores were dichotomized. Following exploratory analysis, we trained supervised regression- and classification models for outcome prediction. Results: Data analysis confirmed significant correlation between the absolute UPDRS-III reduction during Levodopa challenge and after stimulation. But individual improvement was inaccurately predicted with a large range of up to 30 UPDRS III points. Further analysis identified preoperative UPDRS-III/med-off-scores and preoperative Levodopa-improvement as most influential factors. The models for UPDRS-III and sub-scores improvement achieved comparably low accuracy. Conclusions: With large prediction intervals, the Levodopa challenge use for patient counseling is limited, though remains important for excluding non-responders to Levodopa. Despite these deficiencies, the current practice of patient selection is highly successful and builds not only on the Levodopa challenge. However, more specific motor tasks and further paraclinical tools for prediction need to be developed.

Real-time classification of movement patterns of tremor patients.

The process of diagnosing tremor patients often leads to misdiagnoses. Therefore, existing technical methods for analysing tremor are needed to more effectively distinguish between different diseases. For this purpose, a system has been developed that classifies measured tremor signals in real time. To achieve this, the hand tremor of 561 subjects has been measured in different hand positions. Acceleration and surface electromyography are recorded during the examination. For this study, data from subjects with Parkinson's Disease, Essential Tremor, and physiological tremor are considered. In a first signal analysis feature extraction is performed, and the resulting features are examined for their discriminative value. In a second step, three classification models based on different pattern recognition techniques are developed to classify the subjects with respect to their tremor type. With a trained decision tree, the three tremor types can be classified with a relative diagnostic accuracy of 83.14%. A neural network achieves 84.24% and the combination of both classifiers yields a relative diagnostic accuracy of 85.76%. The approach is promising and involving more features of the recorded time series will improve the discriminative value.

The Effect of One Session Split-Belt Treadmill Training on Gait Adaptation in People With Parkinson's Disease and Freezing of Gait.

BACKGROUND: Freezing of gait (FOG) in Parkinson's disease (PD) is associated with gait asymmetry and switching difficulty. A split-belt treadmill may potentially address those deficits. OBJECTIVE: To investigate the immediate and retention effects of one-session split-belt treadmill training (SBT) in contrast to regular tied-belt treadmill training (TBT) on gait asymmetry and adaptation in people with PD and FOG (PD + FOG) and healthy controls (HC). Additionally, to investigate differential effects of 3 SBT protocols and compare different gait adaptation outcomes. METHODS: PD + FOG (n = 45) and HC (n = 36) were randomized to 1 of 3 SBT groups (belt speeds' ratio 0.75:1; 0.5:1 or changing ratios) or TBT group. Participants were tested at Pre, Post, and Retention after one treadmill training session. Gait asymmetry was measured during a standardized adaptation test on the split-belt treadmill. RESULTS: SBT proved beneficial for gait adaptation in PD + FOG and HC (P < .0001); however, HC improved more. SBT with changing ratios demonstrated significant effects on gait adaptation from Pre to Post in PD + FOG, supported by strong effect sizes (d = 1.14) and improvements being retained for 24 hours. Mean step length asymmetry during initial exposure was lower in HC compared with PD + FOG (P = .035) and differentiated best between the groups. CONCLUSIONS: PD + FOG improved gait adaptation after a single SBT session although effects were smaller than in HC. SBT with changing ratios was the most effective to ameliorate gait adaptation in PD + FOG. These promising results warrant future study on whether long-term SBT strengthens adaptation in PD + FOG and has potential to induce a better resilience to FOG. Clinical trial ID: NCT03725215.

Rest tremor revisited: Parkinson's disease and other disorders.

Tremor is the most common movement disorder characterized by a rhythmical, involuntary oscillatory movement of a body part. Since distinct diseases can cause similar tremor manifestations and vice-versa, it is challenging to make an accurate diagnosis. This applies particularly for tremor at rest. This entity was only rarely studied in the past, although a multitude of clinical studies on prevalence and clinical features of tremor in Parkinson's disease (PD), essential tremor and dystonia, have been carried out. Monosymptomatic rest tremor has been further separated from tremor-dominated PD. Rest tremor is also found in dystonic tremor, essential tremor with a rest component, Holmes tremor and a few even rarer conditions. Dopamine transporter imaging and several electrophysiological methods provide additional clues for tremor differential diagnosis. New evidence from neuroimaging and electrophysiological studies has broadened our knowledge on the pathophysiology of Parkinsonian and non-Parkinsonian tremor. Large cohort studies are warranted in future to explore the nature course and biological basis of tremor in common tremor related disorders.