Impact of subthalamic stimulation and medication on proximal and distal bradykinesia in Parkinson's disease.

OBJECTIVE: To evaluate the usefulness of a new instrument for bedside testing of proximal arm and distal finger tapping performance in patients with Parkinson's disease (PD). METHODS: Twenty healthy controls and 25 PD patients with subthalamic nucleus deep brain stimulation were investigated in different treatment conditions using three different tapping paradigms: (1) the standard tapping task of the CAPSIT-PD-protocol; (2) alternate pressing of two buttons on the new board by moving the arm at the elbow and shoulder (proximal tapping), and (3) alternate pressing of two closely collocated buttons on the new board by moving only the index finger (distal tapping) for 30 s. RESULTS: The new tapping board was as sensitive as the standard board to distinguish untreated PD patients from controls. The relative improvements in tapping scores from the off treatment condition were largest for the proximal tapping task. The treatment effects of high frequency stimulation of the subthalamic nucleus or medication alone were comparable, whereas the combined treatment induced significantly higher tapping scores. CONCLUSION: The new tapping board represents a quick and easy to use bedside test, which may be routinely used to probe the efficacy of treatments on different aspects of motor control.

Modulation of specific components of sleep disturbances by simultaneous subthalamic and nigral stimulation in Parkinson's disease.

OBJECTIVE: To compare the effect of simultaneous deep brain stimulation of the subthalamic nucleus and substantia nigra pars reticulata (STN+SNr-DBS) to conventional subthalamic stimulation (STN-DBS) on sleep quality in Parkinson's disease (PD) patients. METHODS: The study was a single-center, randomized, double-blind, cross-over clinical trial to compare the effect of STN-DBS vs. combined STN+SNr-DBS on subjective measures of sleep quality. Fifteen PD patients (2 female, age 62.5 ± 6.7 years) suffering from moderate idiopathic PD (disease duration: 12.0 ± 5.0 years, Hoehn & Yahr stage: 2.2 ± 0.4 in the MED-ON & STN-DBS-ON condition, Hoehn & Yahr stage: 2.6 ± 0.8 in the MED-OFF condition preoperatively) participated in the study. Sleep quality was evaluated in both stimulation conditions using the PDSS-2 score as a self-rating questionnaire covering several aspects of sleep disturbances. RESULTS: PD patients showed mild-moderate sleep disturbances (STN-DBS: PDSS-2 score 17.0 ± 11.0; STN+SNr-DBS: 14.7 ± 9.5) with slight but not significant differences between both stimulation conditions. Considering the different subitems of the PDSS-2, combined STN+SNr stimulation was superior to conventional STN stimulation in improving restless legs symptoms (RLS) at night (STN-DBS = 1.9 ± 2.7 STN+SNr-DBS = 1.0 ± 1.8; W = -2.06, p = 0.039) and immobility at night (STN-DBS = 1.5 ± 1.4 STN+SNr-DBS = 0.6 ± 0.8; W = -2.041, p = 0.041). CONCLUSION: This study demonstrates the safety of STN+SNr-DBS compared to conventional STN-DBS on sleep in general with potential beneficial input on RLS symptoms and akinesia at night.

Impact of Combined Subthalamic Nucleus and Substantia Nigra Stimulation on Neuropsychiatric Symptoms in Parkinson's Disease Patients.

The goal of the study was to compare the tolerability and the effects of conventional subthalamic nucleus (STN) and combined subthalamic nucleus and substantia nigra (STN+SNr) high-frequency stimulation in regard to neuropsychiatric symptoms in Parkinson's disease patients. In this single center, randomized, double-blind, cross-over clinical trial, twelve patients with advanced Parkinson's disease (1 female; age: 61.3 ± 7.3 years; disease duration: 12.3 ± 5.4 years; Hoehn and Yahr stage: 2.2 ± 0.39) were included. Apathy, fatigue, depression, and impulse control disorder were assessed using a comprehensive set of standardized rating scales and questionnaires such as the Lille Apathy Rating Scale (LARS), Modified Fatigue Impact Scale (MFIS), Becks Depression Inventory (BDI-I), Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease Rating Scale (QUIP-RS), and Parkinson's Disease Questionnaire (PDQ-39). Three patients that were initially assigned to the STN+SNr stimulation mode withdrew from the study within the first week due to discomfort. Statistical comparison of data retrieved from patients who completed the study revealed no significant differences between both stimulation conditions in terms of mean scores of scales measuring apathy, fatigue, depression, impulse control disorder, and quality of life. Individual cases showed an improvement of apathy under combined STN+SNr stimulation. In general, combined STN+SNr stimulation seems to be safe in terms of neuropsychiatric side effects, although careful patient selection and monitoring in the short-term period after changing stimulation settings are recommended.

Kinematic effects of subthalamic stimulation on reach-to-grasp movements in Parkinson's disease.

BACKGROUND: Parkinsonian patients demonstrate particular difficulties when performing sequential motor tasks compared to simple movements indicating an important role of the basal ganglia in switching between different motor programs. OBJECTIVE: To investigate the impact of subthalamic stimulation on the kinematics of composed reach-to-grasp movements and on isolated movement segments. METHODS: 11 age matched controls and 16 PD patients with subthalamic stimulation were examined without medication with stimulation switched on and off. All subjects were instructed to perform three different externally cued hand movements: 1) The complete reach-to-grasp movement consisting of hand transport to and precision grip around a target. 2) The isolated reach movement to the grip device 3) The isolated precision grip and button press. Kinematic data were recorded with a 3D ultrasound movement analysis system (CMS 70 P4-V5, Zebris, Germany). RESULTS: The effect of subthalamic stimulation was accentuated during the reach phase compared to the grip formation during the composed movement. Stimulation induced kinematic changes of the composed movement were comparable to those of both isolated submovements. CONCLUSION: Subthalamic stimulation improved certain aspects of all three hand movement types but did not differentially impact the composed reach-to-grasp task compared to the simple submovements. We assume that the complete reach-to-grasp task is encoded in a single generalised motor program which is affected by stimulation.

Startle stimuli exert opposite effects on human cortical and spinal motor system excitability in leg muscles.

Increased excitability of the spinal motor system has been observed after loud and unexpected acoustic stimuli (AS) preceding H-reflexes. The paradigm has been proposed as an electrophysiological marker of reticulospinal tract activity in humans. The brainstem reticular formation also maintains dense anatomical interconnections with the cortical motor system. When a startling AS is delivered, prior to transcranial magnetic stimulation (TMS), the AS produces a suppression of motor evoked potential (MEP) amplitude in hand and arm muscles of healthy subjects. Here we analyzed the conditioning effect of a startling AS on MEP amplitude evoked by TMS to the primary motor leg area. Ten healthy volunteers participated in two experiments that used a conditioning-test paradigm. In the first experiment, a startling AS preceded a suprathreshold transcranial test stimulus. The interstimulus interval (ISI) varied between 20 to 160 ms. When given alone, the test stimulus evoked a MEP amplitude of approximately 0.5 mV in the slightly preinervated soleus muscle (SOL). In the second experiment, the startling AS was used to condition the size of the H-reflex in SOL muscle. Mean MEP amplitude was calculated for each ISI. The conditioning AS suppressed MEP amplitude at ISIs of 30-80 ms. By contrast, H-reflex amplitude was augmented at ISIs of 100-200 ms. In conclusions, acoustic stimulation exerts opposite and ISI-specific effects on the amplitude of MEPs and H-reflex in the SOL muscle, indicating different mechanism of auditory-to-motor interactions at cortical and spinal level of motor system.