Unified Parkinson's Disease Rating Scale-III Research Articles

A nomogram based on neuron-specific enolase and substantia nigra hyperechogenicity for identifying cognitive impairment in Parkinson's disease.

One in four individuals with Parkinson's disease (PD) experience cognitive impairment (CI). However, few practical models integrating clinical and neuroimaging biomarkers have been developed to address CI in PD. This study aimed to evaluate the correlation between circulating neuron-specific enolase (NSE) levels, substantia nigra hyperechogenicity (SNH), and cognitive function in PD and to develop a nomogram based on clinical and neuroimaging biomarkers for predicting CI in patients with PD. A total of 385 patients with PD who underwent transcranial sonography (TCS) from January 2021 to December 2022 at Beijing Tiantan Hospital, Capital Medical University, were recruited as the training cohort. For validation, 165 patients with PD treated from January 2023 to December 2023 were enrolled. Data for SNH, plasma NSE, and other clinical measures were collected, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Logistic regression analysis was employed to select potential risk factors and establish a nomogram. The receiver operating characteristic curve and calibration curve were generated to evaluate the performance of the nomogram. Patients with PD exhibiting CI displayed advanced age, elevated Unified PD Rating Scale-III (UPDRS-III) score, an increased percentage of SNH, higher levels of plasma NSE and homocysteine (Hcy), a larger SNH area, and lower education levels compared to PD patients without CI. Gender [odds ratio (OR) =0.561, 95% confidence interval (CI): 0.330-0.954, P=0.03], age (OR =1.039; 95% CI: 1.011-1.066; P=0.005), education level (OR =0.892; 95% CI: 0.842-0.954; P<0.001), UPDRS-III scores (OR =1.026; 95% CI: 1.009-1.043; P=0.003), plasma NSE concentration (OR =1.562; 95% CI: 1.374-1.776; P<0.001), and SNH (OR =0.545; 95% CI: 0.330-0.902; P=0.02) were independent predictors of CI in patients with PD. A nomogram developed using these six factors yielded a moderate discrimination performance with an area under the curve (AUC) of 0.823 (95% CI 0.781-0.864; P<0.001). The calibration curve demonstrated acceptable agreement between predicted outcomes and actual values. Validation further confirmed the reliability of the nomogram, with an AUC of 0.864 (95% CI: 0.805-0.922; P<0.001). The level of NSE in plasma and the SNH assessed by TCS are associated with CI in patients with PD. The proposed nomogram has the potential to facilitate the detection of cognitive decline in individuals with PD.

Preoperative Attention/Memory Problem Affects the Quality of Life of Parkinson's Disease Patients after Deep Brain Stimulation: A Cohort Study.

The aim of this study was to investigate the impact of nonmotor symptoms (NMS) on the quality of life (QoL) outcome after subthalamic nucleus deep brain stimulation (STN-DBS) at the 1-year follow-up. Ninety-three patients diagnosed with Parkinson's disease (PD), who underwent subthalamic nucleus deep brain stimulation (STN-DBS) between April 2020 and August 2021, were included in this study. Demographic information was gathered through a self-designed questionnaire. The severity of both motor and non-motor symptoms, along with the quality of life (QoL), was assessed using the Unified Parkinson's Disease Rating Scale-III (UPDRS-III), Nonmotor Symptoms Scale (NMSS), and 8-item Parkinson's Disease Questionnaire (PDQ-8), respectively. Significant differences were observed in the UPDRS-III score, NMSS summary index (SI), and subscores of six domains (sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, urinary, and sexual function) between the baseline and the 6- and 12-month follow-ups. The correlation analysis revealed positive correlations between the preoperative NMSS SI and subscores of seven domains (cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastrointestinal, and urinary) and ΔPDQ-8. Moreover, the preoperative PDQ-8 SI (β = 0.869, P < 0.001) and the preoperative attention/memory subscore (β = -0.154, P = 0.026) were predictive of the postsurgery improvement in quality of life (QoL). Deep brain stimulation (DBS) led to an improvement in the patients' nonmotor symptoms (NMS) at the 1-year follow-up, along with a correlation observed between NMS and the patients' quality of life (QoL). Notably, the severity of preoperative attention/memory problems emerged as the most significant predictor of NMS influencing the QoL outcome after STN-DBS at the 1-year follow-up.

Treadmill Training Plus Semi-Immersive Virtual Reality in Parkinson's Disease: Results from a Pilot Study.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders that causes postural instability and gait alterations, such as reduced walking speed, shorter step length, and gait asymmetry, exposing patients to a higher risk of falling. Recently, virtual reality (VR) was added to a treadmill, in order to promote motor functional recovery and neuroplastic processes. Twenty PD patients were enrolled and randomly assigned to two groups: the experimental group (EG) and the control group (CG). In particular, patients in the EG were trained with the C-Mill, an innovative type of treadmill, which is equipped with semi-immersive VR, whereas the CG performed conventional physiotherapy. Patients in both groups were evaluated through a specific motor assessment battery at baseline (T0) and after the training (T1). Comparing pre-(T0) and post-(T1) treatment scores, in the EG, we found statistical significances in the following outcome measures: 6 Minutes Walking Test (6MWT) (p < 0.0005), Timed up and go (TUG right) (p < 0.03), Berg Balance Scale (BBS) (p < 0.006), Tinetti Scale (TS) (p < 0.002), Falls Efficacy Scale- International (FES-I), (p < 0.03) Unified PD Rating Scale-III (UPDRS) (p < 0.002), and Functional Independence Measure (FIM) (p < 0.004). Also, the CG showed statistical significances after the training. Between-group (EG and CG) analysis showed significative statistical differences in 6MWT (p < 0.006), BBS (p < 0.006), TS (p < 0.008), FES-I (p < 0.01), and FIM (p < 0.009). From our results it emerges that both groups (EG and CG) achieved better outcome scores after the treatment, suggesting that both physiotherapy interventions were effective. However, the EG training using VR seemed to have induced more improvements, especially in gait and balance skills. Then, C-Mill could be a valid adjunctive treatment in the context of gait and balance disturbances, which are very common in the PD population.

Spinal Cord Stimulation for Parkinson’s Disease: A Systematic Review and Meta-Analysis of Pain and Motor Outcomes

Background: Spinal cord stimulation (SCS) has been investigated as a potential therapeutic option for managing refractory symptoms in patients with Parkinson’s disease (PD). Objective: This systematic review and meta-analysis aimed to evaluate the safety and efficacy of SCS in PD. Method: A comprehensive literature search was conducted on PubMed and Web of Science to identify SCS studies reporting Unified Parkinson Disease Rating Scale-III (UPDRS-III) or Visual Analogue Scale (VAS) score changes in PD cohorts with at least 3 patients and a follow-up period of at least 1 month. Treatment effect was measured as the mean change in outcome scores and analyzed using an inverse variance random-effects model. The risk of bias was assessed using the Newcastle-Ottawa Scale and funnel plots. Results: A total of 11 studies comprising 76 patients were included. Nine studies involving 72 patients reported an estimated decrease of 4.43 points (95% confidence interval [CI]: 2.11; 6.75, p < 0.01) in UPDRS-III score, equivalent to a 14% reduction. The axial subscores in 48 patients decreased by 2.35 points (95% CI: 1.26; 3.45, p < 0.01, 20% reduction). The pooled effect size of five studies on back and leg pain VAS scores was calculated as 4.38 (95% CI: 2.67; 6.09, p < 0.001), equivalent to a 59% reduction. Conclusions: Our analysis suggests that SCS may provide significant motor and pain benefits for patients with PD, although the results should be interpreted with caution due to several potential limitations including study heterogeneity, open-label designs, small sample sizes, and the possibility of publication bias. Further research using larger sample sizes and placebo-/sham-controlled designs is needed to confirm effectiveness.

Primary progressive apraxia of speech: Clinico-pathological associations of left-right hemispheric dominance (S8.008)

<h3>Objective:</h3> To determine whether there are differences in in demographics, clinicopathologic-neuroimaging or survival, between left-dominant, right-dominant, and symmetric PPAOS. <h3>Background:</h3> Primary progressive apraxia of speech (PPAOS) is a neurodegenerative syndrome associated with neuroimaging abnormalities affecting the lateral premotor cortex (LPC) and supplementary motor area (SMA). It is unclear whether relative greater damage to premotor regions in left/right hemisphere is associated with differences in baseline and/or longitudinal features. <h3>Design/Methods:</h3> Fifty-one prospectively recruited PPAOS patients who completed [¹⁸F]-fluorodeoxyglucose PET scanning were classified as left-dominant, right-dominant, or symmetric, based on visual assessment of the LPC and SMA on FDG-PET by independent raters. Statistical analyses were utilized to compared baseline and longitudinal features. Kaplan-Meyer curves and Cox proportional hazards were used to evaluate survival differences across groups. <h3>Results:</h3> 49% of PPAOS patients were identified as left-dominant, 31% as right-dominant, and 20% as symmetric. At baseline, there were no differences between groups. On longitudinal rates of clinical change, left-dominant PPAOS displayed a slower progression of Parkinsonian symptoms on the Unified Parkinson Disease Rating Scale-III (p=0.047), with a trend for slowest rates of progression in ideomotor apraxia (p=0.06) and motor speech severity (p=0.09) relative to other groups. Right-dominant PPAOS demonstrated the most rapid rates of progression of behavioral disturbances on the Frontal Behavioral Inventory (p=0.02), including disinhibition symptoms (p=0.02) and negative behaviors (p=0.05). The symmetric group had fastest worsening of dysarthria. There were no differences in survival, although a five-year increase in age at onset, but not group classification, was associated with shorter survival (Hazard Ratio = 1.32; p=0.007). Braak neurofibrillary tangle stage differed across groups (p=0.01). While not statistically significant, right-dominant PPAOS tended to have corticobasal degeneration (CBD) and left-dominant PPAOS had progressive supranuclear palsy (PSP) pathology at autopsy. <h3>Conclusions:</h3> Patients with PPAOS and a left-dominant pattern of hypometabolism on FDG-PET have the slowest rate of decline of clinical features. <b>Disclosure:</b> Miss Robinson has nothing to disclose. The institution of Joseph Duffy has received research support from NIH. Joseph Duffy has received publishing royalties from a publication relating to health care. Heather Clark has received personal compensation for serving as an employee of Mayo Clinic. The institution of Heather Clark has received research support from NIH. Heather Clark has received publishing royalties from a publication relating to health care. The institution of Rene Utianski has received research support from NIH. The institution of Dr. Machulda has received research support from NIH. Dr. Botha has received research support from NIH. Dr. Singh has nothing to disclose. Nha Trang Thu Pham has received personal compensation for serving as an employee of Mayo Clinic. Mr. Martin has nothing to disclose. The institution of Dr. Taner has received research support from NIH. Dr. Dickson has nothing to disclose. Dr. Lowe has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AVID Radiopharmaceutical. Dr. Lowe has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Inc. The institution of Dr. Lowe has received research support from AVID Radiopharmaceuticals. Dr. Whitwell has nothing to disclose. Dr. Josephs has nothing to disclose.

The effect of task-oriented circuit training-based telerehabilitation on upper extremity motor functions in patients with Parkinson's disease: A randomized controlled trial

IntroductionUpper extremity functions are impaired in patients with Parkinson's disease (PwPD), which leads to difficulties in activities of daily living (ADL), such as reaching or handwriting. The aim of this study was to investigate the effectiveness of task-oriented circuit training-based telerehabilitation (TOCT-TR) on the upper extremity motor function in PwPD. MethodsIn this randomized controlled trial (RCT) 30 PwPD (aged 45–70 years, Hoehn & Yahr stage I-III) were recruited and randomly allocated into two groups. The TOCT-TR group received home training through video sessions three days/week for six weeks. Additionally, both the TOCT-TR group and the control group (CG) underwent home exercises aimed at improving balance, gait, and mobility three days/week for six weeks. The primary outcome measure was upper extremity motor functions measured with the Nine Hole Peg test (9-HPT), the Jebsen Hand Function Test (JHFT), grip strengths, pinch strengths, and the Unified Parkinson's Disease Rating Scale-III (UPDRS-III). Secondary outcome measures included the UPDRS-II and the quality of life (QoL, PDQ-8). ResultsThis study showed significant group-by-time interactions on the 9-HPT (p < 0.001), the JHFT (p < 0.001), grip strengths (p < 0.001), pinch strengths (p ≤ 0.015), and the UPDRS-III (p = 0.007) in favor of the TOCT-TR. Additionally, the UPDRS-II (p < 0.001), and the PDQ-8 (p = 0.005) improved in both groups. ConclusionThis is the first RCT showing that the TOCT-TR improved upper extremity motor functions, ADL, and QoL in PwPD. The TOCT-TR may help improve the upper extremities of PwPD who have difficulties reaching rehabilitation clinics.

Patients with Parkinson's disease and a history of falls have decreased cerebellar grey matter volumes in the cognitive cerebellum

The objective of this study was to determine if cerebellar gray matter (GM) structure differs between fallers and non-fallers with Parkinson's disease (PD) and their respective association to cognitive function. A total of 48 fallers and 63 non-fallers with PD were identified from the Parkinson's Progression Markers Initiative database. Fallers were categorized as those who self-reported a fall within the past year. Unified Parkinson's Disease Rating Scale-III (UPDRS-III), Montreal Cognitive Assessment (MoCA), Trail Making Test parts A (TMT-A) and B (TMT-B) scores were collected for each patient. Cerebellar GM volumes were derived from magnetic resonance imaging data. Analyses of covariance were used to compare group differences. Partial Pearson's correlations were used to assess the relationship between cerebellar GM volumes to UPDRS-III and cognitive outcomes. Significance was set at P ≤ 0.01. Fallers had significantly decreased GM volumes in lobules V, Crus-1, Crus-2, and VIIb (P<0.01). Cerebellar GM volumes in non-fallers demonstrated little-to-no relationship with UPDRS-III, MoCA, and TMT-B (P>0.01). However, TMT-A performance demonstrated significant, fair association to GM volumes in lobules I–IV, V, VI, Crus-1, and Crus-2 (r=−0.44 – −0.34, P<0.01) in non-fallers. Patients with PD and a history of falls have significantly decreased GM volumes in cerebellar lobules associated with cognitive functions. However, these lobule volumes become disassociated with cognitive function compared to non-fallers.

A Clinical Study of Patients with Primary Parkinson's Disease Undergoing Bilateral Deep Brain Stimulation (STN-DBS) Surgery in the Subthalamic Nucleus under General Anesthesia

To assess the efficacy and safety of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) under general anesthesia and to provide the basis for clinical research related to DBS surgeries under general anesthesia. A total of 60 patients with primary Parkinson's disease who underwent DBS surgery between January 2019 and December 2021at West China Hospital were enrolled for the study. Among them, 30 had the surgery while they were asleep, i.e., under general anesthesia, and 30, while they were awake, i.e., under local anesthesia. All the patients underwent bilateral STN-DBS surgery. Bispectral index (BIS) was used to monitor and control the depth of anesthesia. Microelectrode recording (MER) technology was used to record the characteristic signals of the bilateral subthalamic nuclei and verify their location during the operation. All patients completed the implantation of deep electrodes, connecting wires, and implantable stimulation generator (IPG) at one time. Postoperative thin-slice CT scans were done to reconstruct electrode images and to verify the accuracy of electrode implantation. The Unified Parkinson's Disease Rating Scale-Ⅲ (UPDRS-Ⅲ) was used to evaluate the preoperative vs. postoperative improvement in motor symptoms, and the results of intraoperative MER and the occurrence of surgery-related complications were documented and analyzed. All patients successfully completed the implantation surgery. The electrodes were accurately implanted at the right position and there was no significant difference between the general anesthesia group and the local anesthesia group in UPDRS-Ⅲ scores and medication dosage differences before and after the operation. No intracranial hemorrhage, cerebral infarction, or infection occurred after the operation, and 5 patients had temporary mental and behavioral abnormalities, which disappeared within 48 hours after the operation. The postoperative therapeutic effect of STN-DBS surgery for primary Parkinson's disease under general anesthesia is comparable to that of the traditional STN-DBS surgery under local anesthesia. When the operation is performed under general anesthesia, the incidence of surgery and anesthesia-related complications is low if patients are managed strictly, and patients would also experience improved surgical comfort.

Factors Contributing to Malnutrition in Parkinson's Disease Patients With Freezing of Gait.

Background and PurposeLittle is known about the nutritional status and clinical characteristics of patients with Parkinson's disease with freezing of gait (PDFOG). The purpose of this study was to describe the relationship between nutritional status and characteristics of patients with PDFOG.MethodsIn this cross-sectional study, 178 PDFOG patients were recruited and classified as nutritionally normal or at risk of malnutrition/already malnourished based on their Mini Nutritional Assessment (MNA) scores. Each participant underwent a structured questionnaire, physical examination and routine serum biochemical tests.ResultsWe found that 44.4 and 37.1% of PDFOG patients were malnourished [mini nutritional assessment (MNA) score <17] and at risk of malnutrition (17 ≤ MNA score ≤ 23.5), respectively. Compared to patients with normal nutrition, PDFOG patients with malnutrition and at risk of malnutrition had longer duration of Parkinson's disease (PD) and freezing of gait (FOG), more levodopa equivalent daily doses (LEDD), lower body mass index (BMI), more motor symptoms according to the Unified PD Rating Scale-III (UPDRS-III) and non-motor symptoms according to the PD Non-motor Symptoms Questionnaire (PD-NMS) (P < 0.05). Uric acid, albumin, prealbumin, and total cholesterol (TC) differed between the two groups (P < 0.05). High Hoehn and Yahr (H-Y) stage, high Freezing of Gait Questionnaire (FOGQ) scores, low TC and low uric acid were risk factors for malnutrition in patients with PDFOG.ConclusionOur results showed disease severity, motor symptoms, TC levels and uric acid levels were all associated with nutritional status in patients with PDFOG. This study suggest early discovery of the nutritional status of PDFOG patients is important.

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.

Functional Outcome of Bilateral Subthalamic Nucleus-Deep Brain Stimulation in Advanced Parkinson's Disease Patients: A Prospective Study.

Background:Deep brain stimulation (DBS) is an accepted modality of treatment in patients with Parkinson's disease (PD). Although DBS was approved in advanced PD, it is being done in early PD as well. It was mainly developed to help the patients of PD to overcome the adverse motor effects associated with treatment and treatment failure.Objective:The objective is to study the efficacy of subthalamic nucleus (STN)-DBS procedure in patients with PD.Materials and Methods:This was a prospective, single-center, follow-up observational study using a direct, structured interview of 40 selected PD patients. Preoperative assessment using Unified PD Rating Scale-III (UPDRS-III), Montreal Cognitive Assessment (MOCA), and Parkinson's Disease Questionnaire-39 were done. All the patients underwent DBS. Postoperatively, similar assessment was done during follow-up period of 6 months. The results were analyzed using Student's t-test.Results:The total score of UPDRS-III was reduced by 35% after STN-DBS intervention which was statistically significant (P < 0.05). STN-DBS intervention was successful in significantly reducing all UPDRS-III subscores but failed to reduce the scores in case of postural stability. MOCA scores of the patients were not found to be affected by STN-DBS intervention (P = 0.1466). Similar findings were also observed for MOCA subscores, but there was significant improvement of verbal fluency in all patients. Quality of life(QoL) improved significantly in all patients after STN-DBS intervention in all areas. Lower baseline UPDRS-III scores were found to enhance the QoL both in “off” and “on” state. However, prolonged disease duration and older age at PD onset were found to be hampering factors in the improvement of QoL.Conclusions:STN-DBS is a safe procedure and can be performed in all patients of PD who develop disabling motor fluctuations to improve their QoL irrespective early or advanced disease.

Remote Monitoring of Treatment Response in Parkinson's Disease: The Habit of Typing on a Computer.

The recent advances in technology are opening a new opportunity to remotely evaluate motor features in people with Parkinson's disease (PD). We hypothesized that typing on an electronic device, a habitual behavior facilitated by the nigrostriatal dopaminergic pathway, could allow for objectively and nonobtrusively monitoring parkinsonian features and response to medication in an at-home setting. We enrolled 31 participants recently diagnosed with PD who were due to start dopaminergic treatment and 30 age-matched controls. We remotely monitored their typing pattern during a 6-month (24 weeks) follow-up period before and while dopaminergic medications were being titrated. The typing data were used to develop a novel algorithm based on recursive neural networks and detect participants' responses to medication. The latter were defined by the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) minimal clinically important difference. Furthermore, we tested the accuracy of the algorithm to predict the final response to medication as early as 21 weeks prior to the final 6-month clinical outcome. The score on the novel algorithm based on recursive neural networks had an overall moderate kappa agreement and fair area under the receiver operating characteristic (ROC) curve with the time-coincident UPDRS-III minimal clinically important difference. The participants classified as responders at the final visit (based on the UPDRS-III minimal clinically important difference) had higher scores on the novel algorithm based on recursive neural networks when compared with the participants with stable UPDRS-III, from the third week of the study onward. This preliminary study suggests that remotely gathered unsupervised typing data allows for the accurate detection and prediction of drug response in PD. © 2019 International Parkinson and Movement Disorder Society.

Unveiling the relationship between central parkinsonian pain and motor symptoms in Parkinson's disease.

Pain in Parkinson's disease (PD) is a common and heterogeneous non-motor symptom. Although the characteristics and predictors of pain in general and of central pain in particular are still largely unknown. A semi-structured interview, the Brief Pain Inventory and the Pain Disability Index were used to identify and characterize pain in a consecutive series of 292 PD patients. Unified PD Rating Scale-III, Hoehn & Yahr, Schwab and England Independence Scale and Freezing of Gait Questionnaire were applied to assess motor symptoms and functional independence in off and on conditions. Hospital Anxiety and Depression Scale and Questionnaire of Impulsive-Compulsive Control Disorders were used to screen for anxiety, depression and impulse control disorders. Two hundred and twelve patients (73%) reported pain, which was classified as: musculoskeletal (63%), dystonia-related (27%), central parkinsonian (22%) and/or radicular or neuropathic (9%). Patients with pain had more comorbidities and more severe motor symptoms. Patients with central parkinsonian pain were significantly younger, had earlier disease onset, fewer comorbidities, greater non-axial motor symptom severity in on, more pain-related disability and more relief of pain with antiparkinsonian medication than patients with non-central parkinsonian pain. PD patients with central parkinsonian pain have some distinctive demographic and clinical features, including lower levodopa responsiveness of motor appendicular/limb symptoms to levodopa, associated with greater responsiveness of pain symptoms to these same medications. These findings suggest the need for a more integrated approach to motor and non-motor symptoms in these patients' clinical care. In a consecutive series of 292 patients with PD, almost three quarters of patients with PD reported pain. The study results revealed that pain was related to more severe motor symptoms, anxiety symptoms and comorbidities. Among patients with pain, those with central parkinsonian subtype had distinct demographic and clinical features, including lower levodopa responsiveness for non-axial motor symptoms and greater responsiveness of pain to antiparkinsonian treatment.

King’s Parkinson’s Disease Pain Scale for Assessment of Pain Relief Following Deep Brain Stimulation for Parkinson’s Disease

Pain is a prevalent and debilitating nonmotor symptom of Parkinson's disease (PD) that is often inadequately managed. Deep brain stimulation (DBS) has been shown to relieve pain in PD but an effective method of identifying which types of PD pain respond to DBS has not been established. We examine the effects of DBS on different types of PD pain using the King's Parkinson's disease pain scale (KPDPS), the only validated scale of PD pain. We prospectively followed 18 PD patients undergoing subthalamic nucleus (STN) or Globus pallidus interna (GPi) DBS. Subjects completed the KPDPS, low back disability index (LBDI), and McGill pain questionnaire (MPQ), preoperatively and at six months postoperatively. Subjects underwent the unified Parkinson's disease rating scale-III (UPDRS-III) with preoperative scores ON medication and postoperative scores ON medication/DBS stimulation. Of the 18 patients, a total of 12 subjects had STN DBS and 6 had GPi DBS. As a group, subjects showed improvement in total KPDPS score at six-month postoperative follow-up (p = 0.004). Fluctuation and nocturnal pain were most significantly improved (p = 0.006, 0.01, respectively). Significant improvements were found in fluctuation-related pain domain following GPi DBS. In this pilot study, we are the first group to employ KPDPS to monitor pain relief following DBS in PD patients. We demonstrate that fluctuation-related pain and nocturnal pain significantly improve with DBS. Use of the KPDPS in the future will allow better understanding of how STN and GPi DBS treat PD pain over time.

Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease.

To evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset. The prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further. UPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT (p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy (p < 0.001, p = 0.003, respectively). More ODT patients developed new rest tremor in previously unaffected limbs than those receiving DBS + ODT (p = 0.001). These results suggest the possibility that DBS in early PD may slow rest tremor progression. Future investigation in a larger cohort is needed, and these findings will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD. This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor.

Quality of life outcome after subthalamic stimulation in Parkinson's disease depends on age.

The purpose of this study was to investigate how quality of life outcome after bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) depends on age. In this prospective, open-label, multicenter study including 120 PD patients undergoing bilateral STN-DBS, we investigated the PDQuestionnaire-8 (PDQ-8), Unified PD Rating Scale-III, Scales for Outcomes in PD-motor examination, complications, activities of daily living, and levodopa equivalent daily dose preoperatively and at 5 months follow-up. Significant changes at follow-up were analyzed with Wilcoxon signed-rank test and Bonferroni correction for multiple comparisons. To explore the influence of age post hoc, the patients were classified into 3 age groups (≤59, 60-69, ≥70 years). Intragroup changes were analyzed with Wilcoxon signed-rank and intergroup differences with Kruskal-Wallis tests. The strength of clinical responses was evaluated using effect size. The PDQuestionnaire-8, Scales for Outcomes in PD-motor complications, activities of daily living, and levodopa equivalent daily dose significantly improved in the overall cohort and all age groups with no significant intergroup differences. However, PDQuestionnaire-8 effect sizes for age groups ≤59, 60 to 69, and ≥70 years, respectively, were strong, moderate, and small. Furthermore, PDQuestionnaire-8 domain analyses revealed that all domains except cognition and emotional well-being significantly improved in patients aged ≤59 years, whereas only communication, activities of daily living, and stigma improved in patients aged 60-69 years, and activities of daily living and stigma in patients aged ≥70 years. Although quality of life, motor complications, and activities of daily living significantly improved in all age groups after bilateral STN-DBS, the beneficial effect on overall quality of life was more pronounced and affected a wider range of quality of life domains in younger patients. © 2017 International Parkinson and Movement Disorder Society.

"Asleep" Deep Brain Stimulation Surgery: A Critical Review of the Literature.

Although performing deep brain stimulation (DBS) with the patient under general anesthesia without microelectrode recording (MER) or intraoperative test stimulation (ITS) for movement disorders ("asleep" DBS) has become increasingly popular, its feasibility is based on the untested assumption that stereotactic accuracy correlates with positive clinical outcomes. To investigate outcomes after asleep DBS without MER or neurophysiological testing, we reviewed the medical literature on the topic. We searched PubMed to identify all studies reporting clinical outcomes for patients who underwent DBS without MER or ITS for Parkinson disease (PD) or essential tremor (ET). We identified 9 studies with level 3b (n= 3) or level 4 evidence (n= 6). Eight PD studies (220 patients) reported asleep placement of 431 electrodes (341 subthalamic nucleus, 90 globus pallidus interna). Unified Parkinson Disease Rating Scale motor examination-III scores for 208 patients demonstrated significant improvement (40.2%-65%) at 6-12 months. Thelevodopa equivalent daily dose for 115 patients was significantly reduced (14%-49.3%) at 6-12 months in 103 patients. Two studies with a comparison cohort undergoing "awake" DBS with MER found no differences in postoperative Unified Parkinson Disease Rating Scale-III improvement or levodopa equivalent daily dose reduction. One study of asleep DBS for ET found no difference in functional outcomes between 17 patients undergoing asleep ventral intermediate nucleus DBS and 40 patients undergoing awake placement with ITS. Initial evidence suggests that asleep DBS can be performed safely for PD and ET with good clinical outcomes. Long-term follow-up, larger cohorts, and double-armed studies are needed to validate these initial results.

Graphical Tasks to Measure Upper Limb Function in Patients With Parkinson's Disease: Validity and Response to Dopaminergic Medication.

The most widely used method to assess motor functioning in Parkinson's disease (PD) patients is the unified Parkinson's disease rating scale-III (UPDRS-III). The UPDRS-III has limited ability to detect subtle changes in motor symptoms. Alternatively, graphical tasks can be used to provide objective measures of upper limb motor dysfunction. This study investigated the validity of such graphical tasks to assess upper limb function in PD patients and their ability to detect subtle changes in performance. Fourteen PD patients performed graphical tasks before and after taking dopaminergic medication. Graphical tasks included figure tracing, writing, and a modified Fitts' task. The Purdue pegboard test was performed to validate these graphical tasks. Movement time (MT), writing size, and the presence of tremor were assessed. MT on the graphical tasks correlated significantly with performance on the Purdue pegboard test (Spearman's ρ > 0.65; p < 0.05). MT decreased significantly after the intake of dopaminergic medication. Tremor power decreased after taking dopaminergic medication in most PD patients who suffered from tremor. Writing size did not correlate with performance on the Purdue pegboard test, nor did it change after taking medication. Our set of graphical tasks is valid to assess upper limb function in PD patients. MT proved to be the most useful measure for this purpose. The response on dopaminergic medication was optimally reflected by an improved MT on the graphical tasks in combination with a decreased tremor power, whereas writing size did not respond to dopaminergic treatment.

Prediction of individual clinical scores in patients with Parkinson's disease using resting-state functional magnetic resonance imaging

Neuroimaging holds the promise that it may one day aid the clinical assessment. However, the vast majority of studies using resting-state functional magnetic resonance imaging (fMRI) have reported average differences between Parkinson's disease (PD) patients and healthy controls, which do not permit inferences at the level of individuals. This study was to develop a model for the prediction of PD illness severity ratings from individual fMRI brain scan. The resting-state fMRI scans were obtained from 84 patients with PD and the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) scores were obtained before scanning. The RVR method was used to predict clinical scores (UPDRS-III) from fMRI scans. The application of RVR to whole-brain resting-state fMRI data allowed prediction of UPDRS-III scores with statistically significant accuracy (correlation=0.35, P-value=0.001; mean sum of squares=222.17, P-value=0.002). This prediction was informed strongly by negative weight areas including prefrontal lobe and medial occipital lobe, and positive weight areas including medial parietal lobe. It was suggested that fMRI scans contained sufficient information about neurobiological change in patients with PD to permit accurate prediction about illness severity, on an individual subject basis. Our results provided preliminary evidence, as proof-of-concept, to support that fMRI might be possible to be a clinically useful quantitative assessment aid in PD at individual level. This may enable clinicians to target those uncooperative patients and machines to replace human for a more efficient use of health care resources.

Comparison of a timed motor test battery to the Unified Parkinson's Disease Rating Scale‐III in Parkinson's disease

The most widely used scale currently available for the clinical evaluation of motor dysfunction in Parkinson's disease (PD)-the Unified Parkinson's Disease Rating Scale-III (UPDRS-III) -is time-consuming, subjective, and has suboptimal sensitivity. A brief timed motor test (TMT) battery could possibly overcome these drawbacks. Two hundred eighty-eight PD patients (disease duration 3.1 years; preceding dopaminergic treatment initiation) were assessed with the UPDRS-III and nine TMTs based on aspects of (a) walking, (b) writing, (c) single and double-handed pegboard performance, (d) finger tapping, and (e) rapid alternating forearm movements. We investigated validity, reliability, responsiveness, and feasibility. Completing the TMT battery took less than 5 minutes. The TMT correlated well with UPDRS-III and disease duration. Two factors explained 61% of the TMT variance, the first represented mainly upper extremity function, the second mainly axial/lower extremity function. Cronbach's alpha was equal for the TMT and the UPDRS-III (0.8). Test-retest reliability of the TMT sumscore was 0.93 to 0.89 for measurements separated by 3 up to 24 months, whereas UPDRS-III correlations were 0.88 to 0.84. At group level, a trial using "change from baseline" as endpoint requires only 75% of the patients needed with the UPDRS-III when applying the TMT battery, and 57% using the pegboard dexterity test. At patient level, TMT and UPDRS-III were equally responsive. The TMT battery described here is valid, reliable, and feasible. Compared to the UPDRS-III, it is more objective and more sensitive to change. Therefore, it could be a useful tool for both practical and scientific purposes. (c) 2008 Movement Disorder Society.