Mario Giorgio Rizzone

Deep brain stimulation of the subthalamic nucleus: anatomical, neurophysiological, and outcome correlations with the effects of stimulation

Objectives: Bilateral chronic high frequency stimulation of the subthalamic nucleus (STN), through the stereotactical placement of stimulating electrodes, effectively improves the motor symptoms of severe Parkinsons disease. Intraoperative neurophysiological and clinical monitoring techniques (neuronal electrical activity recording and intraoperative stimulation) may improve and refine the localisation of the nucleus. The objective of this work was to compare the preoperative CT and MRI localisation with the intraoperative neurophysiological identification of STN. The relation between the localisation of the STN and the position of the most effective contact of the permanent quadripolar electrode at a 3 month and 1 year follow up was also studied. Methods: Fourteen consecutive parkinsonian patients were submitted to bilateral implant for STN stimulation. All the patients underwent a standard MRI and stereotactic CT to obtain, by image fusion and localisation software, the stereotactical coordinates of STN. The STN extension and boundaries were identified by a semimicrorecording of the neuronal electrical activity. The definitive quadripolar electrode was positioned to locate at least two contacts within the STN recording area. Intraoperative macrostimulation was performed to confirm the correct position of the electrode. Postoperative clinical evaluation of the effects of stimulation was checked for each contact of the quadripolar electrode testing the improvement on contralateral rigidity to select the best contact. This evaluation was repeated at 3 months and 1 year after surgery. Results: In 35.7% of the procedures it was necessary to perform more than one track to get a recording of neuronal activity consistent with STN. The mean position of the central point of all the 28 STN recording areas in respect of the AC-PC line midpoint was 2.7 mm posterior (SD 0.7), 3.8 mm inferior (SD 1.1), and 11.6 mm lateral (SD 0.9), and the mean distance between the anatomical target and the central point of the STN as defined by intraoperative recording was 0.5 mm (SD 0.5) on the anteroposterior plane, 0.7 mm (SD 0.7) on the lateral plane, and 0.9 mm (SD 0.6) on the vertical plane. At 1 year the mean position of the central point of the most effective contact of the electrode in respect of the AC-PC line midpoint was 1.7 mm posterior (SD 0.9), 1.7 mm inferior (SD 1.5), and 12.3 mm lateral (SD 0.9). Conclusion: The results highlight the role of the intraoperative recording to get a more accurate localisation of the STN in surgery for Parkinsons disease, allowing the identification of the boundaries and of the extension of the nucleus. The most effective contact of the quadripolar electrode was always in the upper part of the STN recording area or immediately above it, suggesting a role of this region in the clinical effectiveness of the STN electrical stimulation.

Expectation modulates the response to subthalamic nucleus stimulation in Parkinsonian patients.

Expectations about future events are known to trigger neural mechanisms that affect both perception and action. Here we report that different and opposite expectations of bad and good motor performance modulate the therapeutic effects of subthalamic nucleus stimulation in Parkinsonian patients who had undergone chronic implantation of electrodes for deep brain stimulation. By analyzing the effects of subthalamic stimulation on the velocity of movement of the right hand, we found hand movement to be faster when the patients expected a good motor performance. The expectation of good performance was induced through a placebo-like procedure, thus indicating that placebo-induced expectations have influence on the treatment outcome. All these effects occurred within minutes, suggesting that expectations induce neural changes very quickly.

Effects of bilateral subthalamic stimulation on gait kinematics and kinetics in Parkinson’s disease

Abstract.Subthalamic nucleus (STN) stimulation, a recent surgical approach to Parkinson’s disease (PD), has been shown to be effective in relieving motor symptoms. The present study carried out a full body gait analysis, during overground walking, on ten PD patients with bilaterally implanted STN stimulation devices. Walking performance was analyzed on the same day, in four conditions (Stim Off–Med Off, Stim On–Med Off, Stim Off–Med On, Stim On–Med On). The results showed that, on average, STN stimulation alone (S+M−) and l -dopa alone (S-M+), significantly increased gait speed, stride length and the lower limb joint Range of Motion (ROM) with respect to the basal condition (S−M−); also cadence was found to play a role in velocity increase, particularly when l -dopa was administered. Both treatments improved pelvis and trunk kinematics, and power production at the ankle and hip joints. The combination of the two treatments (S+M+) produced an additional effect on gait speed, stride length, ROM of knee and ankle joints, pelvis obliquity and trunk inclination. Given the additive and synergistic effects, it can be hypothesized that the two treatments have different mechanisms of action. Our results confirm the findings of earlier studies that employed treadmill walking.

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: comparison of pre- and postoperative neuropsychological evaluation

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of advanced Parkinsons disease (PD). The aim of this study was to assess the effect of the bilateral surgical procedure and STN DBS on the neuropsychological functions. Twenty Parkinsons disease patients underwent a neuropsychological assessment before and 6 months after surgery in four different conditions: medication on (with levodopa) and medication off (without levodopa) during the preoperative period, medication on/stimulation on (levodopa plus stimulators switched on) and medication off/stimulation on (stimulators switched on without levodopa) during the postoperative period. We did not find any significant difference in the four conditions for all the neuropsychological tests, confirming the lack of an overall cognitive decline after surgery. From a neuropsychological point of view, these results seem to indicate that bilateral STN DBS is a safe treatment for advanced PD.

Transient effects of 80 Hz stimulation on gait in STN DBS treated PD patients: A 15 months follow-up study

BACKGROUND Subthalamic nucleus deep brain stimulation (STN DBS) is an effective therapeutic option for advanced Parkinsons disease (PD). Nevertheless, some patients develop gait disturbances despite a persistent improvement of PD segmental symptoms. Recent studies reported that stimulation of STN with low frequencies produced a positive effect on gait disorders and freezing episodes. OBJECTIVE To evaluate the effects of 80 Hz stimulation frequency on gait in PD patients undergoing STN DBS and to determine whether such effects are maintained over time. METHODS We evaluated 11 STN DBS treated PD patients who had developed gait impairment several years after surgery. Gait was assessed by means of the Stand-Walk-Sit (SWS) test. Motor symptoms and activities of daily living were evaluated through the Unified PD Rating Scale (UPDRS). The stimulation frequency was switched from 130 Hz to 80 Hz, adapting the voltage to maintain the same total delivered energy. Patients were assessed at baseline and 3 hours after switching the stimulation frequency to 80 Hz. Follow-up evaluations were carried out after 1, 5, and 15 months. The clinical global improvement scale was rated at every follow-up visit. RESULTS A significant improvement of gait (SWS test) was evident immediately after switching the stimulation frequency to 80 Hz, with no deterioration of PD segmental symptoms. However, gait improvement was no longer detectable by the SWS test at follow-up evaluations 1, 5, and 15 months later. Three patients were switched back to 130 Hz because of unsatisfactory control of motor symptoms. Of the eight patients maintained at 80 Hz up to 15 months, five showed a global improvement and three showed no change. CONCLUSIONS Stimulation frequency at 80 Hz has an immediate positive effect on gait in STN DBS treated patients; however, the objective gait improvement is not maintained over time, limiting the use of this frequency modulation strategy in the clinical setting.

Deep brain stimulation of the subthalamic nucleus in Parkinson's disease: long-term follow-up.

Abstract. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has been shown to be an effective therapy for the treatment of advanced Parkinsons disease (PD). Fortyseven patients were bilaterally implanted for STN DBS and clinically evaluated according to the Core Assessment Program for Intracerebral Transplantations before surgery and 3, 12 and 24 months after surgery. Electrical stimulation led to a significant improvement in motor symptoms and in the quality of life, allowing a significant reduction of dopaminergic drugs with a consequent improvement of drug-induced dyskinesias. Statistical differences were observed between UPDRS parts II, III and IV values and daily levodopa dosage in the pre- and postoperative periods, while no differences were evident between the 3 postoperative conditions.

Impact of subthalamic nucleus stimulation on the initiation of gait in Parkinson's disease

The effects of subthalamic nucleus (STN) stimulation on the anticipatory postural actions associated with the initiation of gait were studied in ten patients with idiopathic Parkinson’s disease undergoing therapeutic deep brain stimulation. Kinematic, dynamic and electromyographic analysis was performed before and while subjects were starting gait in response to an external cue. Effects of STN stimulation on the standing posture preceding the go signal included significant improvement of the vertical alignment of the trunk and shank, decrease of the hip joint moment, backward shift of the center of pressure (CoP) and reduction of abnormal tonic and/or rhythmic activity in the thigh and leg muscles. Responses to bilateral STN stimulation were more consistent than those evoked by unilateral stimulation. Moreover, comparison between postural changes induced by STN stimulation applied prior to the gait initiation cue and during simple quiet standing revealed more significant responses in the former condition. Effects on the actual gait initiation process included shortening of the imbalance phase, larger backward/lateral displacement of CoP and more physiological expression of the underlying anticipatory muscular synergy. Additional changes were shortening of the unloading phase, shortening of the first-swing phase and increase in the length of the first step. Results demonstrate substantial influence of STN stimulation on functionally basic motor control mechanisms. In particular, the evidence of more significant responses upon attention-demanding conditions and the remarkable effects on postural programmes sub-serving feed-forward regulation of the onset of complex multijoint movements, suggests a consistent action on postural sub-systems relying on cognitive data processing and internal models of body mechanics.

Levodopa/carbidopa intestinal gel infusion in advanced Parkinson's disease: a 7-year experience

Levodopa/carbidopa intestinal gel (LCIG) infusion is nowadays becoming an established therapeutic option for advanced Parkinsons disease (PD) patients with fluctuating symptoms unresponsive to conventional oral treatment. As the implementation of LCIG therapy is increasing, there is a need for safety and efficacy data from current clinical practice.

Deep brain stimulation of subthalamic nucleus: behavioural modifications and familiar relations

Abstract The present study investigated behavioural modifications and familiar relations in a group of 15 parkinsonian patients treated with bilateral deep brain stimulation of the subthalamic nucleus. In 70% of the patients, during the first months after surgery we observed a euphoric mood owing to motor sugins amelioration, but a series of problems (fear to come back to the pre-operative condition, sense of failure, slowness in changing the old habits) arose when it was necessary to adjust the parameters of stimulation and the pharmacological therapy to obtain a stable clinical picture. The caregivers showed an aggressive behaviour as reaction to the persistent psychological dependence of the patients. This distressed condition could be the cause of the onset of incomprehensions within the couple.

Quantitative analysis of gait in Parkinson's disease: a pilot study on the effects of bilateral sub-thalamic stimulation

Four patients with Parkinsons disease who had a Subthalamic Nucleus (STN) stimulator implanted and four age-matched controls underwent gait analysis using a three-dimensional system. STN stimulation substantially improved most of the key variables in the patients, without producing inefficient compensatory movements of the trunk. A reduction of ankle power production during push off was the most persistent abnormality seen when the patients were stimulated. We also found a reduction of trunk lateral bending and torsion when the patients were not stimulated when compared with controls.