Parkinson's disease motor subtypes and bilateral GPi deep brain stimulation: One-year outcomes

ObjectiveWe aimed to explore the differences in motor symptoms and quality of life (QOL) outcomes following bilateral globus pallidus internus deep brain stimulation (GPi DBS), across well-defined motor subtypes of Parkinson's disease (PD), to improve clinical decision making.MethodsThis single-center retrospective study investigated bilateral GPi DBS outcomes in 65 PD patients. Outcome measures included the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire (PDQ-39) before and one year after surgery. Outcomes were compared between the tremor-dominant (TD) and postural instability and gait difficulty (PIGD) subtypes and between the TD and akinetic-rigid (AR) subtypes.ResultsFor the entire cohort, motor function (UPDRS III) in the Off-medication state, motor complications (UPDRS IV), activities of daily living (ADL, UPDRS II), and the ADL and discomfort domains of PDQ-39 significantly improved one year following GPi implantation compared to baseline (effect size = 1.32, 1.15, 0.25, 0.45, and 0.34, respectively). GPi DBS improved the Off-medication UPDRS III scores regardless of the motor subtypes. However, compared to the PIGD and AR patients, the TD patients showed greater improvement in overall UPDRS III postoperatively primarily due to greater tremor improvement in the Off-medication state. The outcomes in akinesia, rigidity, axial symptoms and QOL were similar among all subtypes.ConclusionBilateral GPi DBS was effective for advanced PD patients regardless of motor subtypes. Greater tremor improvement in the TD patients accounted for greater Off-medication motor improvement. Longer-term GPi DBS outcomes across different motor subtypes and brain targets should be further studied.     

Combination targeting of subthalamic nucleus and ventral intermediate thalamic nucleus with a single trajectory in deep brain stimulation for tremor-dominant Parkinson’s disease

Deep brain stimulation (DBS) has traditionally been used to target the subthalamic nucleus (STN) or globus pallidus internus (GPi) to treat Parkinson’s disease (PD) and the ventral intermediate thalamic nucleus (VIM) to treat essential tremor (ET). Recent case reports have described targeting both the STN and VIM with a single trajectory and electrode to treat patients with tremor-dominant PD, yet outcome data for this procedure remains sparse. Our objective is to determine the safety and efficacy of combination STN-VIM DBS. We conducted a single-center retrospective case series of all patients who underwent combined STN-VIM DBS. Demographic, perioperative, and outcome data, including Unified Parkinson Disease Rating Scale-III (UPDRS) and tremor scores (OFF-medication), and levodopa equivalent daily dose (LEDD), were collected and analyzed. Nineteen patients underwent this procedure. Patients were 89% male and 11% female, with a mean age of 63.6 years. Mean preoperative UPDRS was 24.1, and LEDD was 811.8. At a mean follow-up of 33.8 months, UPDRS and LEDD decreased by an average of 9.2 (38.2%) and 326.3 (40.2%), respectively. Tremor scores decreased by 4.9 (59.0%), and 58% were able to decrease total medication burden. One patient developed transient left-sided weakness, yielding a complication rate of 5.3%. Combined targeting of STN and VIM thalamus via a single frontal trajectory for tremor-dominant Parkinson’s Disease results in similar UPDRS outcomes to STN DBS and improved control of tremor symptoms. Larger multicenter studies are necessary to validate this as the optimal DBS target for tremor-dominant PD.     

Thalamic stimulation alleviates levodopa-resistant rigidity in a patient with non-Parkinson’s disease parkinsonian syndrome

Deep brain stimulation (DBS) to the thalamic ventrointermediate nucleus (Vim) is a useful treatment in patients with tremor-dominant Parkinson’s disease (PD). Efficacy to alleviate rigidity remains controversial. We report a 65-year-old right-handed man with persistent severe rigidity and bradykinesia on the right side despite daily administration of levodopa/carbidopa (600/60 mg). His right-hand tremor was continuous at rest and present at action. His antiparkinsonian medications appeared ineffective and he reported difficulties with writing and eating. Repeated ¹²³I-meta-iodobenzylguanidine myocardial scintigraphy studies demonstrated a non-PD pattern. He underwent the stereotactic implantation of a DBS electrode into the left Vim. Using contacts 1 and 2 we started continuous unipolar stimulation with a pulse generator implanted in a subclavian pocket. This improved the tremor and the rigidity and bradykinesia of his right hand. Postoperative image analysis revealed the likelihood of simultaneous stimulation of the Vim and the nucleus ventralis oralis posterior. Our findings suggest thalamic stimulation as a therapeutic option for drug-resistant rigidity (and tremor) in patients with parkinsonian syndromes ineligible for DBS targeted at the globus pallidus internus or subthalamic nucleus.     

Combined deep brain stimulation and thalamotomy for tremor-dominant Parkinson’s disease

Although deep brain stimulation (DBS) is an established treatment for Parkinson’s disease, the long-term suppression of tremor is still a challenging issue. We report two patients with tremor-dominant Parkinson’s disease (PD) treated with unilateral thalamotomy of the ventralis intermedius nucleus (Vim) combined with the subthalamic nucleus (STN)-DBS or the posterior subthalamic area (PSA)-DBS. One year after the surgery, thalamotomy of the area from the Vim to the PSA showed improvement not only in tremor but also in rigidity and akinesia. PSA- or STN-DBS with low intensity stimulation eliminated residual PD symptoms. Combined DBS and thalamotomy may provide long-term improvement of the majority of PD symptoms using lower therapeutic stimulation voltages.     

双侧丘脑底核脑深部刺激术治疗帕金森病13例报告

目的 探讨双侧丘脑底核（STN）脑深部刺激术（DBS）治疗帕金森病的临床经验。方法 从2002年到2005年共完成了13例帕金森病的双侧丘脑底核DBS，根据STN解剖学定位，靶点的理论坐标值是X=11-13mm，Y=0-2mm，Z=0-4mm，通过立体定向技术在双侧丘脑底核植入刺激电极，并于锁骨下方植入脑深部电刺激器。结果 随访时间为6个月到3年，3例震颤为主病人的症状完全缓解，即震颤完全消失；僵直和运动迟缓为主要症状者的症状缓解程度达90％以上，其中以四肢肌肉僵直的效果较好，运动迟缓也有明显缓解，但是有1例病人双侧肢运动协调性差。所有患者植物神经功能症状有较明显改善，如便秘、流涎、出汗和浮肿等均有改善。结论 DBS治疗帕金森病，是帕金森病治疗的一个里程碑似的进步。它可以明显地缓解帕金森病的主要症状和体征，对运动迟缓、僵直和震颤等均有较理想的效果。     

The Intraoperative Microlesion Effect Positively Correlates With the Short-Term Clinical Effect of Deep Brain Stimulation in Parkinson's Disease

ObjectiveDuring the surgical procedure of deep brain stimulation (DBS), insertion of an electrode in the subthalamic nucleus (STN) frequently causes a temporary improvement of motor symptoms, known as the microlesion effect (MLE). The objective of this study was to determine the correlation between the intraoperative MLE and the clinical effect of DBS.Materials and MethodsThirty Parkinson's disease (PD) patients with Movement Disorder Society (MDS) Unified Parkinson's Disease Rating Scale (UPDRS) part III (MDS-UPDRS III) scores during bilateral STN-DBS implantation were included in this retrospective study. MDS-UPDRS III subscores (resting tremor, rigidity, and bradykinesia) of the contralateral upper extremity were used. During surgery, these subscores were assessed directly before and after insertion of the electrode. Also, these subscores were determined in the outpatient clinic after 11 weeks on average (on-stimulation). All assessments were performed in an off-medication state (at least 12 hours of medication washout).ResultsPostinsertion MDS-UPDRS motor scores decreased significantly compared to preinsertion scores (p < 0.001 for both hemispheres). The MLE showed a positive correlation with the clinical effect of DBS in both hemispheres (rho = 0.68 for the primarily treated hemisphere, p < 0.001, and rho = 0.59 for the secondarily treated hemisphere, p < 0.01).ConclusionThe MLE has a clinically relevant correlation with the effect of DBS in PD patients. These results suggest that the MLE can be relied upon as evidence of a clinically effective DBS electrode placement.     

Effect of short and long term STN stimulation periods on parkinsonian signs

Currently, no study of subthalamic nucleus (STN) stimulation has compared continuous stimulation with a period of short‐term stimulation, which is frequently employed in the clinic and in research studies. Therefore, this study examined the effects of STN stimulation over 90 min (short) and greater than 3 months (long) on the cardinal signs of Parkinson's disease. The 90 min time period immediately followed a 12 hour withdrawal from both STN stimulation and medication. Ten PD patients who received STN stimulation were studied. Bradykinesia, rigidity, and tremor were evaluated using the UPDRS and motor control measures which included peak velocity (bradykinesia), work (rigidity), and amplitude (tremor). Results showed no difference between 90 min and greater than 3 months of STN stimulation for the UPDRS or motor control measures. This finding confirms that the treatment efficacy that is derived from a relatively short time course of stimulation generalizes to longer time periods of high frequency STN stimulation that patients experience in their daily lives. As such, it is reasonable to evaluate the effect of DBS after 90 min of stimulation in clinical trials and research studies. © 2008 Movement Disorder Society     

Localization of motor and verbal fluency effects in subthalamic DBS for Parkinson's disease

IntroductionSubthalamic nucleus deep brain stimulation (STN DBS) improves cardinal motor symptoms of Parkinson's disease (PD) but can worsen verbal fluency (VF). An optimal site of stimulation for overall motor improvement has been previously identified using an atlas-independent, fully individualized, field-modeling approach. This study examines if cardinal motor components (bradykinesia, tremor, and rigidity) share this identified optimal improvement site and if there is co-localization with a site that worsens VF.MethodsAn atlas-independent, field-modeling approach was used to identify sites of maximal STN DBS effect on overall and cardinal motor symptoms and VF in 60 patients. Anatomic coordinates were referenced to the STN midpoint. Symptom severity was assessed with the MDS-UPDRS part III and established VF scales.ResultsSites for improved bradykinesia and rigidity co-localized with each other and the overall part III site (0.09 mm lateral, 0.93 mm posterior, 1.75 mm dorsal). The optimal site for tremor was posterior to this site (0.10 mm lateral, 1.40 mm posterior, 1.93 mm dorsal). Semantic and phonemic VF sites were indistinguishable and co-localized medial to the motor sites (0.32 mm medial, 1.18 mm posterior, 1.74 mm dorsal).ConclusionThis study identifies statistically distinct, maximally effective stimulation sites for tremor improvement, VF worsening, and overall and other cardinal motor improvements in STN DBS. Current electrode sizes and voltage settings stimulate all of these sites simultaneously. However, future targeted lead placement and focused directional stimulation may avoid VF worsening while maintaining motor improvements in STN DBS.     

Clinician versus machine: Reliability and responsiveness of motor endpoints in Parkinson's disease

BackgroundEnhancing the reliability and responsiveness of motor assessments required to demonstrate therapeutic efficacy is a priority for Parkinson's disease (PD) clinical trials. The objective of this study is to determine the reliability and responsiveness of a portable kinematic system for quantifying PD motor deficits as compared to clinical ratings.MethodsEighteen PD patients with subthalamic nucleus deep-brain stimulation (DBS) performed three tasks for evaluating resting tremor, postural tremor, and finger-tapping speed, amplitude, and rhythm while wearing a wireless motion-sensor unit (Kinesia) on the more-affected index finger. These tasks were repeated three times with DBS turned off and at each of 10 different stimulation amplitudes chosen to yield small changes in treatment response. Each task performance was video-recorded for subsequent clinician rating in blinded, randomized order. Test–retest reliability was calculated as intraclass correlation (ICC) and sensitivity was calculated as minimal detectable change (MDC) for each DBS amplitude.ResultsICCs for Kinesia were significantly higher than those for clinician ratings of finger-tapping speed (p < 0.0001), amplitude (p < 0.0001), and rhythm (p < 0.05), but were not significantly different for evaluations of resting or postural tremor. Similarly, Kinesia scores yielded a lower MDC as compared with clinician scores across all finger-tapping subscores (p < 0.0001), but did not differ significantly for resting and postural tremor.ConclusionsThe Kinesia portable kinematic system can provide greater test–retest reliability and sensitivity to change than conventional clinical ratings for measuring bradykinesia, hypokinesia, and dysrhythmia in PD patients.     

A validated measure of rigidity in Parkinson's disease using alternating finger tapping on an engineered keyboard

IntroductionReliable and accurate measures of rigidity have remained elusive in remote assessments of Parkinson's disease (PD). This has severely limited the utility of telemedicine in the care and treatment of people with PD. It has also had a large negative impact on the scope of available outcomes, and on the costs, of multicenter clinical trials in PD. The goal of this study was to determine if quantitative measures from an engineered keyboard were sensitive and related to clinical measures of rigidity.MethodsSixteen participants with idiopathic PD, off antiparkinsonian medications, and eleven age-matched control participants performed a 30 second repetitive alternating finger tapping task on an engineered keyboard and were assessed with the Unified Parkinson's Disease Rating Scale – motor (UPDRS-III).ResultsThe speed of the key release was significantly slower in the PD compared to control cohorts (p < 0.0001). In the PD cohort key release speed correlated with the lateralized upper extremity UPDRS III rigidity score (r = - 0.58, p < 0.0001), but not with the lateralized upper extremity tremor score (r = - 0.14, p = 0.43).ConclusionsThis validated measure of rigidity complements our previous validation of temporal metrics of the repetitive alternating finger tapping task with the UPDRS III, bradykinesia and with the ability to quantify tremor, arrhythmicity and freezing episodes, and suggests that 30 seconds of alternating finger tapping on a portable engineered keyboard could transform the treatment of PD with telemedicine and the precision of multicenter clinical trials.     

Factors predicting response to dopaminergic treatment for resting tremor of Parkinson's disease

We aimed to evaluate the clinical factors predicting response to dopaminergic treatment for resting tremor in patients with Parkinson's disease (PD). Eighty‐five PD patients with prominent resting tremor, defined as tremors of score greater than 3 in at least one limb on the Unified Parkinson's Disease Rating Scale (UPDRS), were divided into those responsive or nonresponsive to dopaminergic treatment. Responsiveness was defined as a reduction of at least two points for more than 3 months in the UPDRS tremor score. Of the 85 patients, 36 (42.4%) were responsive and 49 (57.6%) were nonresponsive to dopaminergic treatment. Initial UPDRS III score (P = 0.015) and Hoehn and Yahr stage (P = 0.010) were each significantly higher in the RG than in the NRG. UPDRS subscores for rigidity (P = 0.012), bradykinesia (P = 0.021) and postural impairment (P = 0.018) also correlated with responsiveness to dopaminergic treatment. Resting tremor in PD patients was more responsive to dopaminergic treatment when accompanied by moderate degrees of bradykinesia and rigidity than in patients without other prominent parkinsonian features. © 2007 Movement Disorder Society     

Stimulation of the subthalamic nucleus in a patient with Parkinson disease and essential tremor

BACKGROUND: The preferred surgical target for the treatment of Parkinson disease (PD) is either the internal globus pallidus or the subthalamic nucleus (STN); the target for treatment of essential tremor (ET) is the thalamic subnucleus ventralis intermedius (Vim). Some patients with PD have coexistent ET, and the identification of a single surgical target to treat both parkinsonian motor symptoms and ET would be of practical importance. OBJECTIVE: To describe the use of the STN target in deep brain stimulator (DBS) surgery to treat PD motor symptoms and the action-postural tremor of ET. DESIGN: Case report. PATIENT: A 62-year-old man had a greater than 30-year history of action-postural tremor in both hands, well controlled with beta-blockers for more than 20 years. He developed resting tremor, bradykinesia, and rigidity on his right side that progressed to his left side during the past 10 years. Dopaminergic medication improved his rigidity and bradykinesia, with only mild improvement of his resting tremor and no effect on his action-postural tremor. INTERVENTIONS: Left pallidotomy followed by placement of a left DBS in the Vim and subsequent placement of a right STN DBS. MAIN OUTCOME MEASURES: Control of symptoms of PD and ET. RESULTS: The left pallidotomy controlled the patient's parkinsonian motor symptoms on the right side of his body, but did not affect the action-postural component of his tremor. The symptoms on the left side of the body, including both an action-postural and a resting tremor (as well as the rigidity and bradykinesia), improved after placement of a single right STN DBS. CONCLUSION: Placement of an STN DBS should be considered as the procedure of choice for surgical treatment of patients with a combination of PD and ET.     

Neuroimaging and neurophysiological evaluation of severity of Parkinson’s disease

ObjectivesParkinson’s disease (PD) is a neurodegenerative disease presenting characteristic motor features. Severity is usually assessed by clinical symptoms; however, few objective indicators are available. In this study, we evaluated the utility of dopamine transporter (DAT) imaging and subthalamic nucleus (STN) activities as indicators of PD severity.Materials and methodsTwelve hemispheres of ten patients with PD who underwent deep brain stimulation (DBS) were included in this study. Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part 3 scores were used to evaluate clinical severity. The relationship between specific binding ratio (SBR) of DAT imaging and the root mean square (RMS) of STN micro-electrode recording (MER) was evaluated.ResultsA negative correlation was detected between the MDS-UPDRS part 3 scores and SBR (N = 20, R² = 0.418; P = 0.002). With respect to subscores, rigidity (R² = 0.582; P < 0.001) and bradykinesia (R² = 0.378; P = 0.004) showed negative correlation with SBR, whereas tremor showed no correlation (R² = 0.054; P = 0.324) (N = 20). On the other hand, no correlation was found between MER and the MDS-UPDRS part 3 scores in ten hemispheres of six patients.ConclusionDAT findings may be useful in evaluating PD severity, especially rigidity and bradykinesia.     

Two‐year follow‐up on the effect of unilateral subthalamic deep brain stimulation in highly asymmetric Parkinson's disease

Although bilateral subthalamic deep brain stimulation (STN DBS) provides greater relief from the symptoms of Parkinson's disease (PD) than unilateral STN DBS, it has been suggested that unilateral STN DBS may be a reasonable treatment option in selected patients, especially those with highly asymmetric PD. In previous studies on the effect of unilateral STN DBS, the asymmetry of PD symptoms was not prominent and the mean follow‐up durations were only 3 to 12 months. In this study, we report our findings in a series of 8 patients with highly asymmetric PD who were treated with unilateral STN DBS and were followed for 24 months. Serial changes in Unified Parkinson's Disease Rating Scale (UPDRS) motor score and subscores in the ipsilateral, contralateral, and axial body parts were analyzed. Unilateral STN DBS improved the UPDRS motor score and the contralateral subscore in the on‐medication state for 5 nonfluctuating patients and in the off‐medication state for 3 fluctuating patients. However, the ipsilateral subscore progressively worsened and reversed asymmetry became difficult to manage, which led to compromised medication and stimulator adjustment. At 24 months, all the patients were considering the second‐side surgery. Our results suggest that bilateral STN DBS should be considered even in highly asymmetric PD. © 2008 Movement Disorder Society     

Dual threshold neural closed loop deep brain stimulation in Parkinson disease patients

BackgroundClosed loop deep brain stimulation (clDBS) in Parkinson's disease (PD) using subthalamic (STN) neural feedback has been shown to be efficacious only in the acute post-operative setting, using externalized leads and stimulators.ObjectiveTo determine feasibility of neural (N)clDBS using the clinical implanted neurostimulator (Activa? PC + S, FDA IDE approved) and a novel beta dual threshold algorithm in tremor and bradykinesia dominant PD patients on chronic DBS.Methods13 PD subjects (20 STNs), on open loop (ol)DBS for 22 ± 7.8 months, consented to NclDBS driven by beta (13–30 Hz) power using a dual threshold algorithm, based on patient specific therapeutic voltage windows. Tremor was assessed continuously, and bradykinesia was evaluated after 20 min of NclDBS using a repetitive wrist flexion-extension task (rWFE). Total electrical energy delivered (TEED) on NclDBS was compared to olDBS using the same active electrode.ResultsNclDBS was tolerated for 21.67 [21.10–26.15] minutes; no subject stopped early. Resting beta band power was measurable and similar between tremor and bradykinesia dominant patients. NclDBS improved bradykinesia and tremor while delivering only 56.86% of the TEED of olDBS; rWFE velocity (p = 0.003) and frequency (p < 0.001) increased; tremor was below 0.15 rad/sec for 95.4% of the trial and averaged 0.26 rad/sec when present.ConclusionThis is the first study to demonstrate that STN NclDBS is feasible, efficacious and more efficient than olDBS in tremor and bradykinesia dominant PD patients, on long-term DBS, using an implanted clinical neurostimulator and driven by beta power with a novel dual threshold algorithm, based on customized therapeutic voltage windows.     

脑深部刺激电极埋置术治疗帕金森病疗效研究

目的 探讨脑深部刺激电极埋置术治疗帕金森病的疗效及其作用机制。方法 对32例帕金森病患者应用微电极导向立体定向技术,于丘脑底核埋置体外可控性脑深部刺激电极,对其疗效和预后进行随访。结果患者术后僵硬、震颤和运动迟缓等症状明显缓解,术前、术后统一帕金森病评分量表(unified Parkinson's disease ratingscale,UPDRS)运动评分和日常生活能力(activities of daily living,ADL)评分有显著性差异(P<0.01),部分患者由药物引起的开-关现象也有明显缓解;协同服用的多巴胺类药物的用量也有不同程度的减少。所有患者术中及术后均无严重的并发症,术后随访疗效肯定。结论 丘脑底核放置深部脑刺激电极,能明显改善帕金森病患者的临床症状,提高手术的安全性,并发症少。     

MRI verified STN stimulation site – gait improvement and clinical outcome

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective in alleviating Parkinson’s disease (PD) symptoms (tremor, rigidity and bradykinesia) and may improve gait and postural impairment associated with the disease. However, improvement of gait is not always as predictable as the clinical outcome. This may relate to the type of gait impairment or localization of the active DBS contact. Methods: The active contact was visualized on peri‐operative magnetic resonance imaging in 22 patients with idiopathic PD, consecutively treated with bilateral STN DBS. Stimulation site was grouped as either in the dorsal/ventral STN or medial/lateral hereof and anterior/posterior STN or medial/lateral hereof. The localization was compared with relative improvement of clinical outcome (UPDRS‐III). In 10 patients, quantitative gait analyses were performed, and the improvement in gait performance was compared with stimulation site in the STN. Results: Of 44 active contacts, 77% were inside the nucleus, 23% were medial hereof. Stimulation of the dorsal half improved UPDRS‐III significantly more than ventral STN DBS (P = 0.02). However, there were no differences between anterior and posterior stimulation in the dorsal STN. Step velocity and length improved significantly more with dorsal stimulation compared with ventral stimulation (P = 0.03 and P = 0.02). Balance during gait was also more improved with dorsal stimulation compared with ventral stimulation. Conclusions: Deep brain stimulation of the dorsal STN is superior to stimulation of the ventral STN. Possible different effects of stimulation inside the nucleus underline the need for exact knowledge of the active stimulation site position to target the most effective area.     

Deep brain stimulation in Parkinson’s disease

Throughout the past decade, there has been a marked increase in surgical therapies, primarily deep brain stimulation (DBS), for the treatment of advanced Parkinson’s disease (PD). DBS of the thalamus has been shown to be effective in reducing parkinsonian tremor; however, it is not the treatment of choice for PD given the progression of other symptoms such as rigidity and bradykinesia. Stimulation of the globus pallidus or the subthalamic nucleus is safe and efficacious in the long-term treatment of all cardinal symptoms of PD, and they are currently the surgeries of choice. Serious adverse events with DBS can occur in 1% to 2% of patients, infection in 5% to 8% of patients, and hardware complications in approximately 25% of patients. Complications associated with DBS are related to the experience of the surgical center. Referring physicians and patients should be aware of the number of surgical procedures and complication rates of any prospective surgical center.     

Effective long-term subthalamic stimulation in PARK8 positive Parkinson’s disease

Whether patients with genetically defined Parkinson’s disease (PD) may be particularly eligible to benefit from deep brain stimulation of the nucleus subthalamicus (STN-DBS) is currently the subject of debate. We report on a patient with advanced PD due to R793M missense mutation in the LRRK2 gene successfully treated by STN-DBS. Disease onset was at age 42 with bradykinesia, rigidity and rest tremor. During the course of the disease he developed severe motor fluctuations, dyskinesias, postural instability with falls, but preserved levodopa responsiveness. At age 60 the patient was treated by bilateral DBS of the STN. At one year after surgery a 66% improvement of the UPDRS motor score in the off-medication state was determined. During the long-term follow-up there was sustained benefit with 56% improvement of motor score after 8 years. Our report adds evidence that patients with LRRK2 monogenetic Parkinsonism are well suited candidates for DBS treatment and may indicate a potential genetic predictor for positive long-term effect of STN-DBS treatment.     

Quantitative measurements of alternating finger tapping in Parkinson's disease correlate with UPDRS motor disability and reveal the improvement in fine motor control from medication and deep brain stimulation.

The Unified Parkinson's Disease Rating Scale (UPDRS) is the primary outcome measure in most clinical trials of Parkinson's disease (PD) therapeutics. Each subscore of the motor section (UPDRS III) compresses a wide range of motor performance into a coarse-grained scale from 0 to 4; the assessment of performance can also be subjective. Quantitative digitography (QDG) is an objective, quantitative assessment of digital motor control using a computer-interfaced musical keyboard. In this study, we show that the kinematics of a repetitive alternating finger-tapping (RAFT) task using QDG correlate with the UPDRS motor score, particularly with the bradykinesia subscore, in 33 patients with PD. We show that dopaminergic medication and an average of 9.5 months of bilateral subthalamic nucleus deep brain stimulation (B-STN DBS) significantly improve UPDRS and QDG scores but may have different effects on certain kinematic parameters. This study substantiates the use of QDG to measure motor outcome in trials of PD therapeutics and shows that medication and B-STN DBS both improve fine motor control.