"At the beginning of stimulation, high frequency (160-185 Hz) was applied to control the tremor, one of the most prominent symptoms of PD; after the tremor was finally restrained with long-term of stimulation , the relative lower frequency (130-145 Hz) was applied. Additionally, when some of the patients developed the axial symptoms like swallow, speech and gait disorders, the stimulation frequency was reduced (85-115 Hz) further to improve the balance and speech functions, especially in some bradykinesia or rigidity dominated patients, which is in consistent to the recently reported studies [17,18]. "
[Show abstract][Hide abstract] ABSTRACT: Objective
The short-term benefits of bilateral stimulation of the subthalamic nucleus (STN) in patients with advanced Parkinson’s disease (PD) are well documented, but long-term benefits are still uncertain. The aim of this study is to evaluate the outcome of 8 years of bilateral STN stimulation to PD patients.
In this study, 31 consecutive PD patients were treated with bilateral STN stimulation. Their functional status was measured using the Activities of Daily Living section of the Unified Parkinson’s Disease Rating Scale (UPDRS-ADL) at drug on (with medication) and drug off (without medication) states preoperatively and at 1, 5, and 8 years postoperatively. In addition, Levodopa equivalent doses and stimulation parameters were also assessed.
After 8 years of STN stimulation, the UPDRS-ADL scores were improved by 4% at drug off status (P > 0.05) and 22% at drug on status (P < 0.05) compared with baseline; the levodopa daily doses were reduced by 28% (P < 0.05) compared with baseline; the stimulation voltage and pulse width were not changed, but the stimulation frequency was decreased remarkably compared with the 5 years of follow-up. Adverse events were observed in 6 patients, including misplacement of the electrode and skin erosion requiring further surgery. All events were resolved without permanent sequelae. 2 patients died of aspiration pneumonia 6 and 7 years after surgery.
The marked improvement in UPDRS-ADL scores were still observed after 8 years of bilateral STN stimulation with medication.
"The question of whether stimulation at lower frequencies is ineffective or alternatively might actually reinforce abnormal activity is an important one (Baker et al., 2011), for which a definitive answer continues to be sought. Also of importance are the somewhat controversial reports of low frequency stimulation improving gait in PD (Moreau et al., 2008), which has not been widely replicated across groups (Brozova et al., 2009) but has been seen in individual patients. Though not currently amenable to clinician modulation, the influence of stimulation pattern has been investigated in patients, animal models, and in simulated neuronal networks, and this was the focus of Brocker and colleagues in this issue of Experimental Neurology. "
[Show abstract][Hide abstract] ABSTRACT: Deep brain stimulation (DBS) has emerged as an important and potentially powerful treatment option for the management of carefully selected patients with advanced Parkinson's disease (PD) who are not adequately controlled by standard medication therapy. Though considerable advances have been made, the mechanisms underlying the therapeutic effects of DBS remain unclear despite its clinical efficacy. It is now widely held that both excitation and inhibition can occur secondary to stimulation, and it is suspected that abnormal synchronized oscillations may also be important in the mechanism of DBS. Other potentially important processes, including blood flow changes, local and upstream neurogenesis, and the modulation of neurotransmitters through stimulation of bordering astrocytes are also being investigated. Recent research has suggested that the temporal pattern of DBS stimulation is also an important variable in DBS neuromodulation, yet the extent of its influence on DBS efficacy has yet to be determined. As high stimulation frequency alone does not appear to be sufficient for optimal symptom suppression, attention to stimulation pattern might lead to more effective symptom control and reduced side effects, possibly at a lower frequency. Stimulation pattern may be potentially amenable to therapeutic modulation and its role in the clinical efficacy of DBS should be addressed through further focus and research.
"However, individual patients may show poor or no gait improvement after STN implants, even in the short-term period . Inaccurate positioning of the stimulating electrode within the STN  or spread of current to other adjacent regions  may cause stimulation-induced FOG. Falls may be due to either FOG or postural instability may be particularly resistant to both DRT and DBS . "
[Show abstract][Hide abstract] ABSTRACT: Deep brain stimulation (DBS) is considered an established treatment for advanced Parkinson’s disease (PD). Nevertheless, some questions remain open. As different nuclei have been stimulated producing a wide number of effects on motor and non-motor symptoms, the first question relates to the issue of which target should be considered. Long-term and convincing data are available on the effects of subthalamus (STN), globus pallidus internus (GPi), and nucleus ventralis intermedius (Vim) of thalamus whereas less evidences have been collected on other deep brain targets, such as pedunculopontine nucleus, centromedian/parafascicular thalamic complex or zona incerta. A recent trial comparing STN and GPi DBS has not shown any substantial differences between both targets and the reasons for this are still unknown. Indeed most clinicians prefer the STN because of its better motor effect and the potential to reduce drug treatment as suggested by several smaller studies. On the other hand, preliminary data suggest a possibly better effect of GPi-stimulation on gait. Smaller studies also suggest advantages for dyskinetic and possibly older patients for the Gpi as a target. The next question is if earlier treatment may improve the course of PD. A small pilot study was positive and modeling of the effects of DBS earlier in the course of the disease supported such an approach but the pivotal study is still lacking.
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