Results-In all the patients it was impossible to obtain the RCE using 10 and 50 Hz stimulus rates. For all the other stimulus rate values, the intensity-pulse width curves (IPWCs) for the RCE and for the side eVect threshold showed a hyperbolic trend. For every pulse width value, increasing the rate from 90 to 130 and to 170 Hz progressively decreased the intensity of the stimulus necessary to reach the RCE, but the diVerences were not significant. Within the same rate value, the progressive reduction of the stimulus intensity necessary to obtain the RCE, obtained with the lengthening of the pulse width was significant (p<0.05) only comparing 60 with 210 µs and 60 with 450 µs. Conclusions-The findings give some useful indications for the electrical parameter setting in deep brain stimulation of the STN, and some information about the mechanism of action of deep brain stimulation. (J Neurol Neurosurg Psychiatry 2001;71:215-219)

Deep brain stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson's disease. The benefits of bilateral subthalamic stimulation are well documented, and some studies reported outcomes with a follow-up of 5 to 6 years; nevertheless, few data are available beyond 5 years. We report a long-term prospective evaluation of 14 consecutive parkinsonian patients, treated by bilateral subthalamic stimulation for at least 9 years. Motor symptoms, activity of daily living, and motor complications were evaluated by means of the Unified Parkinson's Disease Rating Scale, while cognition and mood were assessed with a specific neuropsychological test battery; medication intake, stimulation parameters, comorbidity, and adverse events were also recorded. Patients were evaluated before surgery and at 1, 5, and ≥ 9 years after surgery. At last follow-up, deep brain stimulation significantly improved the motor score by 42% compared to baseline, whereas activities of daily living were no longer improved; there was a 39% reduction in the dosage of dopaminergic drugs and a 59% improvement of L-dopa-related motor complications. The neuropsychological assessment showed that 4 patients (29%) developed a significant cognitive decline over the follow-up period. These results indicate a persistent effect of deep brain stimulation of the subthalamic nucleus on the cardinal motor symptoms in advanced Parkinson's disease patients in the long-term; however, a worsening of patients' disability, mainly due to disease progression, was observed.

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 Parkinson's 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 Parkinson's 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.

Background: Deep Brain Stimulation of the Subthalamic Nucleus (STN-DBS) is an effective treatment for Parkinson's disease (PD), but only few studies investigated its long-term efficacy. Furthermore, little is known about the role of PD-subtype on STN-DBS long-term outcome.Objective: To report the results of a long-term follow-up (mean 11 years, range 10-13) on 26 patients bilaterally implanted in two centres. Methods:Patients were assessed preoperatively and 1, 5 and 11 years after the implant by the Unified Parkinson's Disease Rating Scale (UPDRS) and a battery of neuropsychological tests. Stimulation parameters, drugs dosages, non-motor symptoms and adverse events were also recorded.Results: At 11 years, stimulation significantly improved the motor symptoms by 35.8%, as compared to the preoperative off-state. Motor complications were well controlled, with a 84.6% improvement of dyskinesias and a 65.8% improvement of motor fluctuations. Despite this, the UPDRS-II-on score worsened by 88.5%, mainly for the worsening of poorly levodopa-responsive symptoms. More than 70% of the patients performed in the normal range in most of the neuropsychological tests, despite the development of dementia in 22.7%. Age at disease onset, axial subscore in off-condition and presence of REM behaviour disorder at baseline were found to be associated with a higher risk of developing disability over time. Conclusions:Our study confirms the long-term safety and efficacy of STN-DBS in PD. Nevertheless, the functionality of patients worsens over time, mainly for the onset and progression of levodopa-resistant and non-motor symptoms. The role of PD-subtype seems to be relevant in the long-term outcome.

Clinical findings in Parkinson's disease suggest that most patients progressively develop disabling non-levodopa-responsive symptoms during the course of the disease. Nevertheless, several heterogeneous factors, such as clinical phenotype, age at onset and genetic aspects may influence the long-term clinical picture. In order to investigate the main features of long-term Parkinson's disease progression, we studied a cohort of 19 subjects treated with subthalamic nucleus deep brain stimulation after >20 years of disease, reporting clinical and neuropsychological data up to a mean of 30 years from disease onset. This group of patients was characterized by an early onset of disease, with a mean age of 38.63 years at Parkinson's disease onset, which was significantly lower than in the other long-term subthalamic nucleus deep brain stimulation follow-up cohorts reported in the literature. All subjects were regularly evaluated by a complete Unified Parkinson's Disease Rating Scale, a battery of neuropsychological tests and a clinical interview, intended to assess the rate of non-levodopa-responsive symptom progression. Clinical data were available for all patients at presurgical baseline and at 1, 3 and 5 years from the subthalamic nucleus deep brain stimulation surgical procedure, while follow-up data after >7 years were additionally reported in a subgroup of 14 patients. The clinical and neuropsychological performance progressively worsened during the course of follow-up; 64% of patients gradually developed falls, 86% dysphagia, 57% urinary incontinence and 43% dementia. A progressive worsening of motor symptoms was observed both in 'medication-ON' condition and in 'stimulation-ON' condition, with a parallel reduction in the synergistic effect of 'medication-ON/stimulation-ON' condition. Neuropsychological data also showed a gradual decline in the performances of all main cognitive domains, with an initial involvement of executive functions, followed by the impairment of language, reasoning and memory. Thirty years after the disease onset, most patients presented non-levodopa-responsive symptoms, although the effect of both subthalamic nucleus deep brain stimulation and dopaminergic therapies still showed significant efficacy on the main disease cardinal features. Nevertheless, compared with other subthalamic nucleus deep brain stimulation follow-up studies, which included patients with a shorter disease duration at the time of surgery, a higher prevalence of axial and non-levodopa-responsive symptoms was observed in the long-term evaluations, confirming that several complex aspects underlie the development of non-motor symptoms and other features of Parkinson's disease progression, even in patients with an early disease onset and a prior long-lasting response to dopaminergic therapies.

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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.

LCIG infusion is effective for the long-term treatment of advanced PD patients and exerts a positive and clinically significant effect on motor complications with a relatively low dropout rate.