Motor Complications In Parkinson's Disease Research Articles

Does Delaying Levodopa Prevent Motor Complications in Parkinson's Disease? A Meta-Analysis.

There has been a long debate whether delaying treatment with levodopa prevents motor complications in Parkinson's disease (PD). We performed a meta-analysis on randomized clinical trials (RCTs) that compared early- versus delayed-start treatment with levodopa in PD. A systematic review was conducted in PubMed, EMBASE, and Web of Science databases from inception to July 1, 2023. Only RCTs that compared early and delayed levodopa treatment in PD were included. Non-randomized comparisons from follow-up studies were included as well. Our primary outcomes were occurrence of overall motor complications, motor fluctuations, and dyskinesias. Seven studies with a total of 1149 patients (636 in the early-start group and 513 in the delayed-start) were included in our analysis. There was no difference between groups regarding motor complications (OR 1.39; 95% CI: 0.68-1.72; P = 0.37) or dyskinesias (OR 1.52; 95% CI: 0.90-2.57; P = 0.11). Motor fluctuations occurred less frequently in the early-start group (OR 0.70; 95% CI: 0.52-0.95; P = 0.02). Nonetheless, on subgroup analysis of dopamine agonists, rate of dyskinesias was smaller in the delayed-start group (OR 1.82; 95% CI: 1.08-3.07; P = 0.03). Delaying treatment with levodopa does not seem to prevent levodopa-related motor complications in PD. Adjunct treatment with dopamine agonists may reduce the need for higher doses of levodopa and thus reduce the risk for dyskinesias but this practice is often associated with a higher frequency of adverse effects related to dopamine agonists.

Professor ZHUANG Lixing's experience of integrated acupuncture and medication approach to treat motor complications in Parkinson's disease based on the alternation of "movement and stillness"

This paper introduces Professor ZHUANG Lixing's experience in treating motor complications of Parkinson's disease (PD) with acupuncture combined with medication. Based on the characteristics of the alternation of "movement and stillness" in PD motor complications, Professor ZHUANG divides these complications into three distinct periods: "movement" stage, "stillness" stage and "alternation" stage, and proposes an integrated approach of acupuncture and medication, with staged treatment tailored to each period. The main acupoints include Jin's three needles to regulate spirit (four spirit needles, Shenting [GV 24], Yintang [GV 24+], Shenmen [HT 7], Sanyinjiao [SP 6]), along with hand tremor three needles (Hegu [LI 4], Quchi [LI 11], Dingchan), foot tremor three needles (Yinlingquan [SP 9], Yanglingquan [GB 34], Taichong [LR 3]), and Du's three needles (Dazhui [GV 14], Jinsuo [GV 8], Mingmen [GV 4]). The primary medicinal formulas include Lingjiao Gouteng decoction, Banxia Baizhu Tianma decoction, Bazhen decoction combined with Buzhong Yiqi decoction, Sini decoction combined with Yougui pills, and Xiaochaihu decoction. This integrated approach effectively alleviates the motor symptom fluctuations in PD patients, helping them maintain a stable life.

Motor Complications in Parkinson's Disease: Results from 3343 Patients Followed for up to 12 Years.

Motor complications are well recognized in Parkinson's disease (PD), but their reported prevalence varies and functional impact has not been well studied. To quantify the presence, severity, impact and associated factors for motor complications in PD. Analysis of three large prospective cohort studies of recent-onset PD patients followed for up to 12 years. The MDS-UPDRS part 4 assessed motor complications and multivariable logistic regression tested for associations. Genetic risk score (GRS) for Parkinson's was calculated from 79 single nucleotide polymorphisms. 3343 cases were included (64.7% male). Off periods affected 35.0% (95% CI 33.0, 37.0) at 4-6 years and 59.0% (55.6, 62.3) at 8-10 years. Dyskinesia affected 18.5% (95% CI 16.9, 20.2) at 4-6 years and 42.1% (38.7, 45.5) at 8-10 years. Dystonia affected 13.4% (12.1, 14.9) at 4-6 years and 22.8% (20.1, 25.9) at 8-10 years. Off periods consistently caused greater functional impact than dyskinesia. Motor complications were more common among those with higher drug doses, younger age at diagnosis, female gender, and greater dopaminergic responsiveness (in challenge tests), with associations emerging 2-4 years post-diagnosis. Higher Parkinson's GRS was associated with early dyskinesia (0.026 ≤ P ≤ 0.050 from 2 to 6 years). Off periods are more common and cause greater functional impairment than dyskinesia. We confirm previously reported associations between motor complications with several demographic and medication factors. Greater dopaminergic responsiveness and a higher genetic risk score are two novel and significant independent risk factors for the development of motor complications.

Deep Brain Stimulation for Parkinson's Disease‐the Developing World's Perspective

AbstractBackgroundDeep brain stimulation (DBS) is the most widely used device‐assisted therapy in patients with moderately advanced stages of Parkinson's disease (PD) experiencing motor complications. Only a minority of eligible patients get the opportunity to undergo DBS in the developing world.ObjectivesTo examine the proportion and characteristics of patients with motor complications of PD who are willing for DBS and who undergo surgery.MethodsPatients with motor complications of PD eligible for DBS over a five‐year study period (2016–2020) were included. The demographic, clinical and socio‐economic characteristics and information on their status in 2021 were collected and analyzed.ResultsAmong 1017 patients, 223 had motor symptoms qualifying for DBS and follow‐up information available. Only 78 (35%) opted for surgery. The willing patients had higher socioeconomic status, were older and had longer duration of PD and motor complications, more freezing of gait, cognitive symptoms, and neuropsychiatric disturbances. 37 of them were found unfit during pre‐operative work‐up; only 41 (18%) with motor complications were finally taken up for DBS. Age, duration or severity of motor symptoms did not differ between patients who were finally selected for surgery and those who were not.ConclusionsLess than one‐fifth of our patients with motor complications of PD finally underwent DBS. The patients appeared to wait till the late stages of PD, before making a decision on availing surgical treatment. The delay resulted in nearly half of them being found unfit in pre‐operative work‐up. Our findings may enable clinicians to counsel eligible patients more efficiently.

Identification and quantitative assessment of motor complications in Parkinson's disease using the Parkinson's KinetiGraph™.

Effective management and therapies for the motor complications of Parkinson's disease (PD) require appropriate clinical evaluation. The Parkinson's KinetiGraph™ (PKG) is a wearable biosensor system that can record the motion characteristics of PD objectively and remotely. The study aims to investigate the value of PKG in identifying and quantitatively assessing motor complications including motor fluctuations and dyskinesia in the Chinese PD population, as well as the correlation with the clinical scale assessments. Eighty-four subjects with PD were recruited and continuously wore the PKG for 7 days. Reports with 7-day output data were provided by the manufacturer, including the fluctuation scores (FS) and dyskinesia scores (DKS). Specialists in movement disorders used the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-IV (MDS-UPDRS IV), the wearing-off questionnaire 9 (WOQ-9), and the unified dyskinesia rating scale (UDysRS) for the clinical assessment of motor complications. Spearman correlation analyses were used to evaluate the correlation between the FS and DKS recorded by the PKG and the clinical scale assessment results. Receiver operating characteristic (ROC) curves were generated to analyze the sensitivity and specificity of the FS and DKS scores in the identification of PD motor complications. The FS was significantly positively correlated with the MDS-UPDRS IV motor fluctuation (items 4.3-4.5) scores (r = 0.645, p < 0.001). ROC curve analysis showed a maximum FS cut-off value of 7.5 to identify motor fluctuation, with a sensitivity of 74.3% and specificity of 87.8%. The DKS was significantly positively correlated with the UDysRS total score (r = 0.629, p < 0.001) and the UDysRS III score (r = 0.634, p < 0.001). ROC curve analysis showed that the maximum DKS cut-off value for the diagnosis of dyskinesia was 0.7, with a sensitivity of 83.3% and a specificity of 83.3%. The PKG assessment of motor complications in the PD population analyzed in this study has a significant correlation with the clinical scale assessment, high sensitivity, and high specificity. Compared with clinical evaluations, PKG can objectively, quantitatively, and remotely identify and assess motor complications in PD, providing a good objective recording for managing motor complications.

Serotonin in synucleinopathies

Dysfunction of the serotonergic system represents an important feature in synucleinopathies like Parkinson disease (PD), dementia with Lewy bodies (DLB) and Multiple system atrophy (MSA). Serotonergic fibers from the raphe nuclei (RN) extend broadly throughout the central nervous system, innervating several brain areas affected in synucleinopathies. Alterations of the serotonergic system are associated with non-motor symptoms or motor complications in PD as well as with autonomic features of MSA. Postmortem studies, data from transgenic animal models and imaging techniques greatly contributed to the understanding of this serotonergic pathophysiology in the past, even leading to preclinical and clinical candidate drug tests targeting different parts of the serotonergic system. In this article, we review most recent work extending the knowledge of the serotonergic system and highlighting its relevance for the pathophysiology of synucleinopathies.

Effect of glycine transporter 1 inhibition with bitopertin on parkinsonism and L-DOPA induced dyskinesia in the 6-OHDA-lesioned rat

Dyskinesia remains an unmet need in Parkinson's disease (PD). We have previously demonstrated that glycine transporter 1 (GlyT1) inhibition with ALX-5407 reduces dyskinesia and slightly improves parkinsonism in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned marmoset. Here, we sought to determine the effect of bitopertin, a clinically-tested GlyT1 inhibitor, on parkinsonism and dyskinesia in the 6-hydroxydopamine (6-OHDA)-lesioned rat. To do so, we assessed the effect of bitopertin on parkinsonism as monotherapy and as adjunct to a low dose of L-3,4-dihydroxyphenylalanine (L-DOPA). We then assessed the efficacy of bitopertin on dyskinesia in the context of acute challenge and chronic administration studies. Lastly, we evaluated whether de novo treatment with bitopertin, started concurrently with L-DOPA, would diminish the development of dyskinesia. We discovered that bitopertin (0.3 mg/kg), when administered alone, reduced the severity of parkinsonism by 35% (P < 0.01). As adjunct to a low dose of L-DOPA, bitopertin (3 mg/kg) enhanced the anti-parkinsonian effect of L-DOPA by 36% (P < 0.05). Moreover, the acute addition of bitopertin (0.03 mg/kg) to L-DOPA reduced dyskinesia by 27% (P < 0.001), and there was no tolerance to the anti-dyskinetic benefit after 4 weeks of daily administration. Lastly, bitopertin (0.03 mg/kg) started concurrently with L-DOPA, also attenuated the development of dyskinesia, by 33% (P < 0.01), when compared to L-DOPA alone. Our results suggest that GlyT1 inhibition may simultaneously reduce parkinsonism and L-DOPA-induced dyskinesia and represents a novel approach to treat, possibly prevent, motor complications in PD.

Long-term Effectiveness of Adjuvant Treatment With Catechol-O-Methyltransferase or Monoamine Oxidase B Inhibitors Compared With Dopamine Agonists Among Patients With Parkinson Disease Uncontrolled by Levodopa Therapy

Many people with Parkinson disease (PD) develop motor complications that are uncontrolled by levodopa dose adjustment. Among these patients, it is uncertain which drug class is more effective as adjuvant therapy. To compare the long-term effects on patient-rated quality of life of adding a dopamine agonist vs a dopamine reuptake inhibitor (DRI), either a monoamine oxidase type B (MAO-B) inhibitor or a catechol-O-methyltransferase (COMT) inhibitor, to levodopa therapy for the treatment of patients with motor complications of PD. This pragmatic semifactorial (2 × 1) randomized clinical trial recruited from 64 neurology and geriatric clinics (62 in the United Kingdom, 1 in the Czech Republic, and 1 in Russia) between February 23, 2001, and December 15, 2009. A total of 500 patients with idiopathic PD who developed uncontrolled motor complications and did not have dementia were randomly assigned on a 1:1:1 basis using a computerized minimization program. Data were analyzed between 2017 and 2020. Open-label dopamine agonist, MAO-B inhibitor, or COMT inhibitor. Primary outcomes were scores on the 39-item Parkinson's Disease Questionnaire (PDQ-39) mobility domain and cost-effectiveness. Outcomes were assessed before study entry, at 6 and 12 months after randomization, and annually thereafter. Repeated-measures and log rank analyses were used in an intention-to-treat approach. Among 500 participants, the mean (SD) age was 73.0 (8.2) years; 314 participants (62.8%) were men. Over a median of 4.5 years (range, 0-13.3 years) of follow-up, the participants in the dopamine agonist group had a mean PDQ-39 mobility score that was 2.4 points (95% CI, -1.3 to 6.0 points) better than that of the combined MAO-B and COMT groups; however, this difference was not significant (P=.20). With regard to DRIs, participants in the MAO-B group had mean PDQ-39 mobility scores that were 4.2 points (95% CI, 0.4-7.9 points; P=.03) better than those of the COMT group and EuroQol 5-dimension 3-level (EQ-5D-3L) utility scores that were 0.05 points (95% CI, 0.003-0.09 points; P=.04) better than the COMT group. Nonsignificant improvements were found in the PDQ-39 summary index (mean difference, 2.2 points; 95% CI, -0.2 to 4.5 points; P=.07) along with nonsignificant reductions in dementia (rate ratio [RR], 0.70; 95% CI, 0.47-1.03; P = .07) and mortality (RR, 0.76; 95% CI, 0.56-1.03; P=.07). When dopamine agonists were compared with MAO-B inhibitors only, the outcomes were similar. In this study, patient-rated quality of life was inferior when COMT inhibitors were used as adjuvant treatment compared with MAO-B inhibitors or dopamine agonists among people with PD who experienced motor complications that were uncontrolled by levodopa therapy. The MAO-B inhibitors produced equivalent disease control, suggesting that these agents may be underused as adjuvant therapy. isrctn.org Identifier: ISRCTN69812316; EU Clinical Trials Register Identifier: 2005-001813-16.

Surgical Treatment of Parkinson's Disease: Devices and Lesion Approaches.

Surgical treatments have transformed the management of Parkinson's disease (PD). Therapeutic options available for the management of PD motor complications include deep brain stimulation (DBS), ablative or lesioning procedures (pallidotomy, thalamotomy, subthalamotomy), and dopaminergic medication infusion devices. The decision to pursue these advanced treatment options is typically done by a multidisciplinary team by considering factors such as the patient's clinical characteristics, efficacy, ease of use, and risks of therapy with a goal to improve PD symptoms and quality of life. DBS has become the most widely used surgical therapy, although there is a re-emergence of interest in ablative procedures with the introduction of MR-guided focused ultrasound. In this article, we review DBS and lesioning procedures for PD, including indications, selection process, and management strategies.

A non-linear deterministic model of action selection in the basal ganglia to simulate motor fluctuations in Parkinson's disease.

Motor fluctuations and dyskinesias are severe complications of Parkinson's disease (PD), especially evident at its advanced stage, under long-term levodopa therapy. Despite their strong clinical prevalence, the neural origin of these motor symptoms is still a subject of intense debate. In this work, a non-linear deterministic neurocomputational model of the basal ganglia (BG), inspired by biology, is used to provide more insights into possible neural mechanisms at the basis of motor complications in PD. In particular, the model is used to simulate the finger tapping task. The model describes the main neural pathways involved in the BG to select actions [the direct or Go, the indirect or NoGo, and the hyperdirect pathways via the action of the sub-thalamic nucleus (STN)]. A sensitivity analysis is performed on some crucial model parameters (the dopamine level, the strength of the STN mechanism, and the strength of competition among different actions in the motor cortex) at different levels of synapses, reflecting major or minor motor training. Depending on model parameters, results show that the model can reproduce a variety of clinically relevant motor patterns, including normokinesia, bradykinesia, several attempts before movement, freezing, repetition, and also irregular fluctuations. Motor symptoms are, especially, evident at low or high dopamine levels, with excessive strength of the STN and with weak competition among alternative actions. Moreover, these symptoms worsen if the synapses are subject to insufficient learning. The model may help improve the comprehension of motor complications in PD and, ultimately, may contribute to the treatment design.

What Predicts Different Kinds of Nonadherent Behavior in Elderly People With Parkinson's Disease?

Background: Detailed knowledge about nonadherence to medication could improve medical care in elderly patients. We aimed to explore patterns and reasons for nonadherence in people with Parkinson's disease (PD) aged 60 years and older.Methods: Detailed clinical data and adherence (German Stendal Adherence with Medication Score) were assessed in 230 patients with PD (without dementia). Descriptive statistics were used to study reasons for nonadherence in detail, and general linear models were used to study associations between clusters of nonadherence and clinical parameters.Results: Overall, 14.2% (n = 32) of the patients were fully adherent, 66.8% (n = 151) were moderately nonadherent, and 19.0% (n = 43) showed clinically meaningful nonadherence. In the multivariable analysis, nonadherence was associated with a lower education level, higher motor impairment in activities of daily living, higher number of medications per day, and motor complications of PD. Three clusters of nonadherence were observed: 59 (30.4%) patients reported intentional nonadherence by medication modification; in 72 (37.1%) patients, nonadherence was associated with forgetting to take medication; and 63 (32.5%) patients had poor knowledge about the prescribed medication. A lower education level was mainly associated with modification of medication and poorer knowledge about prescribed medication, but not with forgetting to take medication. Patients with motor complications, which frequently occur in those with advanced disease stages, tend to be intentionally nonadherent by modifying their prescribed medication. Increased motor problems and a higher total number of drugs per day were associated with less knowledge about the names, reasons, and dosages of their prescribed medication.Conclusions: Elderly patients with PD report many reasons for intentional and non-intentional nonadherence. Understanding the impact of clinical parameters on different patterns of nonadherence may facilitate tailoring of interventions and counseling to improve outcomes.

What can we learn from the effect of trihexyphenidyl on motor fluctuations during continuous levodopa-carbidopa intestinal gel infusion (LCIG)? – First documented case

Motor fluctuations can be seen even during treatment with continuous levodopa-carbidopa intestinal gel infusion (LCIG). We report on a middle-aged man with advanced Parkinson's disease (PD) on LCIG in which motor fluctuations have been improved with an anticholinergic. To the best of our knowledge, there have been no previous LCIG cases reported with motor fluctuations responding to non-dopaminergic agent, which might reveal some clues to its pathophysiology. Long-term oral levodopa treatment is associated with development of potentially disabling motor complications including motor fluctuations and dyskinesias in the majority of patients with PD. It has been suggested that motor complications are related to the nonphysiological restoration of brain dopamine with intermittent administration of standard oral levodopa. LCIG significantly reduces “off” time and increases “on” time without dyskinesia in comparison to standard oral levodopa through consistent plasma concentration of levodopa to restore brain dopamine in a more physiological manner. However, it has been reported that PD patients on LCIG often worsen during the afternoon hours, even with stable plasma concentration of levodopa. This raises the possibility that additional factors to dopamine deficiency could play a role in occurrence of motor fluctuations. Here we offer a hypothesis that altered cholinergic signaling could also be involved in the pathophysiology of motor fluctuations, based on our clinical evidence that anticholinergic drug has eliminated motor fluctuations during LCIG in a patient with PD. Further studies for non-dopaminergic along with dopaminergic signaling may be needed to better understand the pathophysiological basis of motor complications in PD.

Functional and dysfunctional impulsivities changes after deep brain stimulation of the subthalamic nucleus

We investigated changes of impulsivity after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) patients, distinguishing functional from dysfunctional impulsivity and their contributing factors. DBS-STN is routinely used to treat motor complications in PD [1] . However, its impact on impulsivity in PD patients is controversial [2] , [3] , [4] . Data of 33 PD patients treated by DBS-STN were studied before and 6 months after surgery: motor impairment, medication (dose and dopaminergic agonists), cognition, mood and occurrence of impulse control disorders. Impulsivity was assessed by the Dickman scale, which distinguishes functional impulsivity (FI), reflecting the potential for reasoning, premeditation and rapid action when the situation requires it, and dysfunctional impulsivity (DFI), reflecting the lack of prior reasoning, even when the situation demands it. The location of DBS leads was studied on postoperative MRI using a deformable histological atlas and by compartmentalization of the STN. After DBS-STN, dysfunctional impulsivity was significantly increased (mean pre- and postoperative DFI scores 1.9 ± 1.6 and 3.5 ± 2.4, P Our study suggests that DBS-STN may have a different impact on both dimensions of impulsivity, worsening pathological impulsivity without altering physiological impulsivity. The increase in dysfunctional impulsivity may be favoured by the location of the electrode in the ventral, limbic, part of the STN.

Chronological View of Peak and Diphasic Dyskinesia, Wearing Off and Freezing of Gait in Parkinson's Disease.

Dyskinesia, wearing off (WO) and freezing of gait (FOG) are troublesome complications degrading quality of life in the course of Parkinson's disease (PD). This study evaluated the gross chronological trend of 4 motor complications - peak dose dyskinesia (PDSK), diphasic dyskinesia (DDSK), WO and FOG in a large PD population with stratification by age at disease onset according to the PD duration. The motor complications of 1212 Korean PD patients were analyzed using Kaplan-Meier curves and Cox proportional hazards models. PDSK and WO appeared first as motor complications and showed accelerated development around the 5 year-PD-duration, while DDSK showed a rather constant development over time and FOG developed around the 10 year-disease duration at an accelerated rate (p < 0.001). A younger age at PD onset predicted an earlier appearance of PDSK, DDSK and WO (p < 0.001), while an older age at onset (≥60 years) was a predictor for FOG (p = 0.014). Motor complications developed with a distinguishing inclination over the PD duration. This study provides insight into the chronological trend of motor complications in PD at a glance.

From medications to surgery: advances in the treatment of motor complications in Parkinson's disease.

Motor complications are responsible for the large burden of disability and poor quality of life in Parkinson’s disease (PD). The pulsatile nature of stimulation with oral dopaminergic therapies due to relatively short pharmacokinetic profiles and dysfunctional gastrointestinal absorption have been attributed to the development of PD motor complications. In this review, we will provide an overview of the pharmacologic and surgical therapies currently available and under investigation for the treatment of motor fluctuations and dyskinesia.

Contemporary Options for the Management of Motor Complications in Parkinson's Disease: Updated Clinical Review.

Parkinson's disease (PD) is a chronic, progressive condition affecting around 1% of the population older than 60years. Upon long-term treatment with levodopa, the mainstay of treatment in PD, most patients, especially younger ones exposed to higher doses, will experience symptoms related to end-of-dose deterioration, peak-dose dyskinesias, and other motor fluctuations. Therapeutic strategies are grounded on modification of oral levodopa pharmacokinetics to extend levodopa benefit and development of new routes of drug delivery (e.g., levodopa/carbidopa intestinal gel infusion) or long-acting formulations of existing dopaminergic drugs to prolong the duration of striatal dopamine receptors stimulation. As our understanding of the pathophysiology of motor complications evolves, our therapeutic armamentarium is actively expanding and the focus of research is now actively pointing to the new non-dopaminergic agents acting both within the basal ganglia and in other brain regions (e.g., drugs acting on glutamate, GABA, serotonin, and calcium channels). Despite the fact that trials comparing the different therapeutic strategies are lacking, we aimed at devising practical evidence- and experience-guided suggestions for the clinical management of motor complications, emphasizing that this should always be an individualized endeavor. This review summarizes the pharmacological management of motor complications in PD, including new formulations and routes of delivery, and the newer released drugs such as istradefylline, opicapone, safinamide, and zonisamide. Advanced therapeutic strategies for selected cases such as treatment with apomorphine and surgical techniques (deep brain stimulation) are also discussed. A comprehensive knowledge of the available options and evidence is fundamental for the successful management of these challenging complications.

Battery longevity of neurostimulators in Parkinson disease: A historic cohort study

BackgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established treatment for motor complications in Parkinson disease (PD). Since 2012, the nonrechargeable dual-channel neurostimulator available in France seems to have shorter battery longevity compared to the same manufacturer's previous model. ObjectiveThe aim of this study was to evaluate the battery longevity of older and more recent neurostimulators from the same manufacturer and to explore factors associated with battery life variations. Materials and methodsWe retrospectively studied our cohort of PD patients who underwent STN DBS between 1987 and 2017. We collected data concerning neurostimulator replacements and parameters. We compared the survival of the first device available, Kinetra® and the current one, Activa-PC® (Medtronic Inc.) and estimated the factors that had an impact on battery longevity through a Cox logistic regression. ResultsThree hundred sixty-four PD patients received a total of 654 DBS STN neurostimulators: 317 Kinetra® and 337 Activa-PC®. The survival analysis, using the Kaplan-Meier estimator, showed a difference between the curves of the two devices (log-rank test; p < 0.001). The median survival of an Activa-PC® neurostimulator was 1666 days, while it was 2379 days for a Kinetra®.After adjustment, according to the multivariate analysis, the main factors associated with battery lifetime were: the neurostimulator type; the number of subsequent neurostimulator implantations; the total electrical energy delivered (TEED); and sex. ConclusionThe Kinetra® neurostimulator lifetime is 2.5 years longer than the Activa-PC®. The type of the device, the high TEED and the number of subsequent neurostimulator implantations influence battery longevity most. These results have medical-economic implications since the survival of PD patients with DBS increases over years.

STN vs. GPi deep brain stimulation for tremor suppression in Parkinson disease: A systematic review and meta-analysis

ObjectiveTo compare subthalamic nucleus (STN) deep brain stimulation (DBS) with globus pallidus interna (GPi) DBS for tremor suppression in Parkinson disease (PD). BackgroundDBS is an effective surgical therapy that has been shown to provide significant benefit for motor symptoms in PD. Currently, two main structures targeted to treat motor complications in PD are the STN and GPi. Although some groups traditionally favor STN over GPi for tremor suppression, evidence demonstrating superiority in long-term tremor control is limited. MethodsWe performed a systematic review for all randomized trials comparing STN vs GPi DBS in PD that were published before March 2017. Five studies were examined in a random effects model meta-analysis. We conducted moderator variable analysis to determine if there was a treatment effect difference for STN versus GPi. ResultsWe compared DBS ON versus OFF and found a significant overall standardized difference mean effect: Effect Size = 0.36; 95% CI = 0.316–0.395; P < 0.0001. These findings indicate that DBS reduced tremor symptoms in PD patients with a medium effect size. Moderator variable analysis of STN vs GPI revealed two significant standardized effect sizes: STN effect size = 0.38 and GPi effect size = 0.35. A Z-test showed that effect sizes between the STN and GPi were not significantly different (P = 0.56). ConclusionsDBS is effective in reducing tremor in PD patients regardless of stimulation target. However, the degree of tremor suppression in STN DBS versus GPi DBS was equivalent.

The significance of uric acid in the diagnosis and treatment of Parkinson disease: An updated systemic review.

Background:Parkinson disease (PD) is a neurodegenerative disease characterized by chronic and progressive loss of dopaminergic neurons in substansia nigra pars compacta. Oxidative stress is proposed to play a critical role in the pathogenesis of PD. Uric acid (UA), as an important physiological antioxidant, is identified a molecular predictor associated with a decreased risk and a slower disease progression for PD and potential neuroprotectant of PD by increasing epidemiological and clinical evidences. Within this review, we will present a comprehensive overview of the data linking UA to PD in recent years.Methods:We searched PubMed, EMBASE, Web of Science databases for relevant studies. Any observational or experimental studies that evaluated UA and PD were our goal of searching the electric databases.Results:Twelve studies that evaluated UA and PD were identified in this review. We reviewed the roles of UA in the pathogenesis of PD, the association of UA with morbidity, severity/progression, nonmotor symptoms, motor complications of PD, with an attempt to provide new ideas for diagnosis and treatment in PD.Conclusion:Our findings supported that lots of clinical and epidemiological data observed lower UA levels in PD patients. Manipulation of UA or its precursors’ concentration could be effective to treat or prevent PD. However, it is still suspectable that higher UA levels are better enough to PD patients. Furthermore, for the complex nature of PD and its heterogeneous genetic and environmental influences, it is inadequate for just manipulating UA in treating the disease.

Dopamine Agonists and Impulse Control Disorders: A Complex Association.

Impulse control disorders (ICDs) are a well-known adverse effect of dopamine agonists (DAAs). This critical review aims to summarize data on the prevalence and factors associated with the development of an ICD simultaneous to DAA use. A search of two electronic databases was completed from inception to July 2017. The search terms were medical subject headings (MeSH) terms including “dopamine agonists” AND “disruptive disorders”, “impulse control disorders”, or “conduct disorders”. Articles had to fulfill the following criteria to be included: (i) the target problem was an ICD; (ii) the medication was a dopaminergic drug; and (iii) the article was an original article. Of the potential 584 articles, 90 met the criteria for inclusion. DAAs were used in Parkinson’s disease (PD), restless legs syndrome (RLS) or prolactinoma. The prevalence of ICDs ranged from 2.6 to 34.8% in PD patients, reaching higher rates in specific PD populations; a lower prevalence was found in RLS patients. We found only two studies about prolactinoma. The most robust findings relative to the factors associated with the development of an ICD included the type of DAA, the dosage, male gender, a younger age, a history of psychiatric symptoms, an earlier onset of disease, a longer disease duration, and motor complications in PD. This review suggests that DAA use is associated with an increased risk in the occurrence of an ICD, under the combined influence of various factors. Guidelines to help prevent and to treat ICDs when required do exist, although further studies are required to better identify patients with a predisposition.