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.     

Influence of motor symptoms upon the quality of life of patients with Parkinson's disease

We studied the impact of various motor and nonmotor symptoms upon quality of life in patients with Parkinson's disease (PD). The study comprised 110 patients with PD (age: 68.6 years, course of the disease: 7.6 years). The Unified Parkinson Disease Rating Scale (UPDRS; I-IV) and Parkinson's Disease Questionnaire (PDQ-39) were recorded. We recorded the correlations between years of disease and UPDRS IV, as well as PDQ-39 and UPDRS I, II, III and IV. Introduction of all variables into a linear regression model showed that 3 variables accounted for 51% of the variance in PDQ-39. Mental condition, gait disorders and complications of dopaminergic drugs are the variables that most affect the quality of life of patients with PD.     

Evaluation of acupuncture in the treatment of Parkinson's disease: a double-blind pilot study.

As many as 40% of patients with Parkinson's disease (PD) use some form of complementary medicine during the course of their illness, and many try acupuncture. One nonblinded study of the effects of acupuncture in PD suggested that it might be helpful for some aspects of PD. We performed a double-blind, randomized, pilot study comparing acupuncture to a control nonacupuncture procedure to determine the effects of acupuncture upon a variety of PD-associated symptoms. Fourteen patients with Stage II or III PD received acupuncture or a control nonacupuncture protocol. Before and after treatment, patients were evaluated using the Motor subscale of the Unified Parkinson's Disease Rating Scale (UPDRS), the Parkinson's Disease Questionnaire (PDQ-39), and the Geriatric Depression Scale. There were no statistically significant changes for the outcomes measured. In the patients who received acupuncture, nonsignificant trends toward improvement were noted in the Activities of Daily Living score of the PDQ-39, the PDQ-39 Summary Index(c) 2005 Movement Disorder Society.     

The effects of random whole-body-vibration on motor symptoms in Parkinson's disease

It is well known that applying vibrations to men influences multiple physiological functions. The authors analysed post effects of whole-body-vibration (WBV) on motor symptoms in Parkinson's disease (PD). Sixty-eight persons with PD were randomly subdivided into one experimental and one control group. Motor symptoms were assessed by the UPDRS (Unified Parkinson's Disease Rating Scale) motor score. A cross-over design was used to control treatment effects. The treatment consisted of 5 series of whole-body-vibration taking 60 seconds each. On average a highly significant (p<0.01) improvement of 16.8% in the UPDRS motor score was found in the treatment group. Only marginal changes (p>0.05) were found in the control group. The cross-over procedure showed comparable treatment effects (14.7% improvement after treatment). With respect to different symptom clusters only small changes were found in limb akinesia and cranial symptoms. By contrast, tremor and rigidity scores were improved by 25% and 24%, respectively. According to the structure of symptom changes it is unlikely that these effects are explainable on peripheral sensory level, exclusively. With respect to the findings of other studies one can speculate about changes in activation of the supplementary motor area and in neurotransmitter functions.     

Low‐fat versus ketogenic diet in Parkinson's disease: A pilot randomized controlled trial

Background : Preliminary evidence suggests that diet manipulation may influence motor and nonmotor symptoms in PD, but conflict exists regarding the ideal fat to carbohydrate ratio. Objectives : We designed a pilot randomized, controlled trial to compare the plausibility, safety, and efficacy of a low‐fat, high‐carbohydrate diet versus a ketogenic diet in a hospital clinic of PD patients. Methods : We developed a protocol to support PD patients in a diet study and randomly assigned patients to a low‐fat or ketogenic diet. Primary outcomes were within‐ and between‐group changes in MDS‐UPDRS Parts 1 to 4 over 8 weeks. Results : We randomized 47 patients, of which 44 commenced the diets and 38 completed the study (86% completion rate for patients commencing the diets). The ketogenic diet group maintained physiological ketosis. Both groups significantly decreased their MDS‐UPDRS scores, but the ketogenic group decreased more in Part 1 (?4.58 ± 2.17 points, representing a 41% improvement in baseline Part 1 scores) compared to the low‐fat group (?0.99 ± 3.63 points, representing an 11% improvement) (P < 0.001), with the largest between‐group decreases observed for urinary problems, pain and other sensations, fatigue, daytime sleepiness, and cognitive impairment. There were no between‐group differences in the magnitude of decrease for Parts 2 to 4. The most common adverse effects were excessive hunger in the low‐fat group and intermittent exacerbation of the PD tremor and/or rigidity in the ketogenic group. Conclusions : It is plausible and safe for PD patients to maintain a low‐fat or ketogenic diet for 8 weeks. Both diet groups significantly improved in motor and nonmotor symptoms; however, the ketogenic group showed greater improvements in nonmotor symptoms. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.     

帕金森病患者冻结步态的危险因素及对生活质量的影响

目的：调查帕金森病(PD)患者冻结步态(FOG)的相关危险因素及对生活质量的影响.方法于2014年1月~2016年1月,对我院神经科门诊就诊的 PD 患者,以问卷的方式,调查患者的一般情况、运动症状、非运动症状和治疗情况,分析 PD 患者 FOG 的相关影响因素及其对生活质量的影响.结果共纳入107例符合条件的 PD 患者,平均发病年龄(59．07±10．46)岁,平均年龄(64．29±9.77)岁,病程2．00~8．00年,中位值4．00年.64例(59．8％)患者出现 FOG,其中男37例(57．8％).与未出现 FOG 的 PD 患者比较,FOG 患者病程长、UPDRS－Ⅱ评分高、“开”期 UPDRS－Ⅲ评分高、“开”期改良 Hoehn& Yahr 分级(H－Y 分级)高、症状波动和剂峰异动症多见、Epworth 嗜睡评分量表(ESS)评分高、快速动眼睡眠行为异常问卷(香港版)(RBDQ－HK)评分高、Beck 抑郁量表(BDI)评分高,差异均有统计学意义(P ＜0．05).调整性别和调查时年龄后,多因素 Logistic 回归分析发现病程长[1．12(1．01~1．25),P ＝0．034]、H － Y 分级高[4．13(1．90~8．98),P ＜0．001]、统一 PD 评分量表(UPDRS)－Ⅱ评分高[1．23(1.12~1．35),P ＜0．001]、UPDRS－Ⅲ评分高[1．06(1．03~1．09),P ＜0.001]、症状波动[3．98(1．68~9．43),P ＝0．002]、剂峰异动症[10．71(1．35~85．23),P ＝0．025]、RBDQ－HK评分高[1．03(1．00~1.60),P ＝0．023]和 BDI 评分高[1．08(1．03~1．14),P ＝0．004]等因素与 FOG 显著相关.同时,合并 FOG 患者 PDQ－39总分更高,除社会支持外,FOG 对其他维度均存在显著影响(P ＜0．05).结论 FOG在 PD 患者中十分常见,病程、疾病严重程度、症状波动、剂峰异动症、RBD 和抑郁状态可能是 PD 患者发生 FOG 的独立危险因素,FOG 可显著降低 PD 患者的生活质量.     

Movement Disorder Society Unified Parkinson Disease Rating Scale experiences in daily living: Longitudinal changes and correlation with other assessments

The Movement Disorder Society (MDS) commissioned a revision of the UPDRS with the goals of improving instructions and definitions, more accurately evaluating milder features, and assessing patient‐reported outcomes and nonmotor features. To date, no study has evaluated longitudinal changes in components of the MDS‐UPDRS over time or correlated these with changes in other scales of various symptoms. We assessed Parts I and II of the MDS‐UPDRS (non‐Motor and Motor Experiences of Daily Living [nM‐EDL, M‐EDL]) as well as a number of other scales of motor, cognitive and behavioral function in a large population of patients (n = 383) with early‐ to mid‐stage Parkinson's disease (PD) who had previously participated in a trial of a putative disease‐modifying agent. Both parts of a MDS‐UPDRS showed significant change over the 3‐year follow‐up period, with M‐EDL scores declining to a greater extent than nM‐EDL. Both the scores and their changes over time correlated relatively well with other rating scales of similar disease aspects. Modest correlations with the original version of the UPDRS supported the increased attention to nonmotor symptoms as well as milder levels of severity in the MDS‐UPDRS. The M‐EDL was much more sensitive to change over time in these early‐ to mid‐stage patients than the original UPDRS Activities of Daily Living (ADL) scale. Finally, we showed no change over time in a small group of individuals with dopamine transporter single‐photon emission computed tomography scans without evidence for dopamine deficiency. The nM‐EDL and M‐EDL components of the MDS‐UPDRS provide an effective, relevant measure of change in the broad spectrum of symptoms of PD over the first decade of the disease. © 2013 International Parkinson and Movement Disorder Society     

Validation of the MDS-UPDRS Part I for nonmotor symptoms in Parkinson's disease

The UPDRS has been the main outcome measure in studies of PD. Modifications have been made to improve scale properties and represent the breadth of manifestations of PD, particularly nonmotor symptoms (NMS), resulting in the Movement Disorder Society's revision of the UPDRS (MDS-UPDRS). This study was undertaken to determine the validity of MDS-UPDRS Part I (nonmotor experiences of daily living). The MDS-UPDRS and a number of validated scales for the NMS in PD were used in 94 patients with PD from Hoehn and Yahr stage I to V. We assessed reliability, floor and ceiling effects, and correlations with validated scales for the nonmotor symptoms of PD. MDS-UPDRS Part I showed high internal consistency (Cronbach's alpha: 0.85), small floor and ceiling effects (2% floor and 0% ceiling effect), and good concurrent validity (correlation with the original UPDRS Part I: r = 0.81, P < 0.001). The standardized z-score of the MDS-UPDRS Part I score demonstrated high convergent validity with the composite z-score of nonmotor scales (r = 0.89, P < 0.0001), and the two subscores based on the original factor analysis of Part I also had high correlations with the composite z-scores of corresponding nonmotor scales (depression, anxiety, apathy factor score: r = 0.72, P < 0.0001; other nonmotor features factor score: r = 0.87, P < 0.0001). Our data demonstrate that the MDS-UPDRS Part I total score has a strong relationship with a composite score of validated scales for the nonmotor aspects of PD.     

P型和C型多系统萎缩的急性多巴反应性研究

目的研究P型和C型多系统萎缩（MSA）对左旋多巴的急性反应性。方法对P型MSA患者18例、C型MSA患者13例和帕金森病（PD）患者23例行急性阶梯式左旋多巴试验，药物剂量依次为左旋多巴／苄丝肼50mg／12．5mg、100mg／25mg、150mg／37．5mg、200mg／50mg和300mg／75mg。以UPDRS运动分量表作为评价标准，计算UPDRS运动评分平均最大改善率并比较各组患者的多巴反应性。结果左旋多巴／苄丝肼剂量为。100mg／25mg、150．mg／37．5mg、200mg／50mg和300mg／75mg时，MSA-P型组和MSA—C型组韵UPDRS运动评分平均最大改善率均显著低于PD组，MSA-P型组高于MSA-C型组。MSA-P型组患者随服用左旋多巴／苄丝肼剂量增加UPDRS评分平均最大改善率呈逐渐增高趋势，而MSA-C型不同剂量间UPDRS评分平均最大改善率差异无统计学意义。结论MSA-P型组具有剂量依赖的急性多巴反应性，而MSA-C型组基本无急性多巴反应性。     

双侧丘脑底核脑深部电刺激对PD患者焦虑症状的短期影响

目的探讨双侧丘脑底核脑深部电刺激(STN-DBS)对帕金森病(PD)患者焦虑症状及生活质量的短期影响。方法对上海交通大学附属瑞金医院功能神经外科中心自2017年8月至2019年8月行双侧STN-DBS治疗的39例PD患者,分别于术前、术后1个月和末次随访时进行贝克焦虑自评量表(BAI)、贝克抑郁自评量表(BDI)评分,于术前和术后末次随访时进行帕金森病患者生活质量问卷-8项(PDQ-8)评分,采用统计学方法分析各节点间评分的差异,以及评分改善程度间的相关性;并进一步依据术前BAI评分将患者分为无焦虑组(n=18)、轻度焦虑组(n=10)、中度焦虑组(n=8)和重度焦虑组(n=3),以进行亚组分析。结果(1)39例患者术后1个月及末次随访时的BAI评分[14(8,20)分、9(3,14)分]均明显低于术前[16(9,27)分],术后末次随访时的BDI评分[8(6,16)分]及PDQ-8评分[3(2,6)分]均明显低于术前[15(8,21)分、9(6,13)分],差异均有统计学意义(P<0.05)。(2)相关性分析显示,术后末次随访时的BAI评分较术前的改善程度与BDI评分的改善程度呈正相关关系(rs=0.722,P=0.000),也与术前BDI评分及术前PDQ-8评分呈负相关关系(rs=-0.714,P=0.000;rs=-0.378,P=0.018)。(3)亚组分析显示,轻度焦虑组和中度焦虑组患者中,术后末次随访时的BAI评分均明显低于术前,差异均有统计学意义(P<0.05);轻度焦虑组、中度焦虑组与重度焦虑组患者的术后末次随访时的BAI评分较术前的改善程度均明显高于无焦虑组,差异均有统计学意义(P<0.05)。结论双侧STN-DBS能在短期内显著改善PD患者的焦虑症状,提高其生活质量,提示STN参与了PD患者焦虑症状的神经机制。     

Efficacy of combining levodopa with entacapone on quality of life and activities of daily living in patients experiencing wearing-off type fluctuations

OBJECTIVES: To compare the efficacy of levodopa/dopa decarboxylase inhibitor (DDCI) plus entacapone with levodopa/DDCI plus placebo on measures of parkinsonian disability and health-related quality of life (QoL) in subjects with Parkinson's disease (PD) experiencing motor fluctuations. MATERIALS AND METHODS: A double-blind, placebo-controlled phase IV study was performed in 270 PD patients randomized to receive either entacapone 200 mg or placebo with each dose of their current levodopa regimen. The primary variables were the Unified Parkinson's Disease Rating Scale (UPDRS) part II activities of daily living (ADL) and the Parkinson's Disease Questionnaire (PDQ)-39 summary index. UPDRS parts I, III-VI, Global Assessment of Change, PDQ-39 subscores, and the Short-Form (SF)-36 and the European Quality of Life five-dimension questionnaire (EQ-5D) were included as secondary variables. RESULTS: There was a significant improvement in ADL scores with levodopa/DDCI/entacapone compared with levodopa/DDCI/placebo at 5 and 13 weeks (-2.3 vs -0.7, respectively; P = 0.0001). However, no significant differences were observed between treatments using the PDQ-39 summary index. UPDRS part III (motor) scores significantly decreased in the levodopa/DDCI/entacapone group compared with the levodopa/DDCI/placebo group (-5.0 vs -2.9, respectively; P = 0.03). Similarly, the change in the investigators Global Assessment was significantly greater (P = 0.004) in the levodopa/DDCI/entacapone group. There were no significant differences between treatments for any of the PDQ-39 subscores, the SF-36 variables or the EQ-5D utility score. CONCLUSIONS: Levodopa combined with entacapone demonstrated good efficacy in terms of ADL, global function, motor performance and was well tolerated. However, this short-term study did not generate significant improvements in QoL.     

Post hoc analysis of the Exenatide‐PD trial—Factors that predict response

Exenatide, a glucagon‐like peptide‐1 agonist and a licensed treatment for Type 2 diabetes significantly reduced deterioration in motor symptoms in patients with Parkinson's disease in a randomized, placebo‐controlled trial. In addition, there were trends favouring the exenatide group in assessments of nonmotor symptoms, cognition, and quality of life. The aim of this exploratory post hoc analysis was to generate new hypotheses regarding (a) whether candidate baseline factors might predict the magnitude of response to exenatide; and (b) whether the beneficial effects of exenatide reported for the overall population are consistent in various subgroups of patients. Univariate and multivariate analyses were conducted to determine possible predictors of motor response to exenatide in this cohort. Potential treatment by subgroup interactions for changes in; motor severity, nonmotor symptoms, cognition, and quality of life after 48‐weeks treatment with exenatide were evaluated among post hoc subgroups defined by age, motor phenotype, disease duration, disease severity, body mass index (BMI), and insulin resistance. In the subgroup analyses, exenatide once‐weekly was associated with broadly improved outcome measures assessing motor severity, nonmotor symptoms, cognition, and quality of life across all subgroups, however, tremor‐dominant phenotype and lower Movement Disorder Society‐Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) Part‐2 scores predicted greatest motor response to exenatide and there was an indication that patients with older age of onset and disease duration over 10 years responded less well. While patients with a range of demographic and clinical factors can potentially benefit from exenatide once‐weekly, these data support an emphasis towards recruiting patients at earlier disease in future planned clinical trials of gluacagon‐like peptide‐1 (GLP‐1) receptor agonists in Parkinson's disease (PD).     

SPECT measurement of iodine-123-beta-CIT binding to dopamine and serotonin transporters in Parkinson's disease: correlation with symptom severity.

Iodine-123-beta-CIT (2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane) binds with high affinity to dopamine (DA) and serotonin (5-HT) transporters. This study examined the correlation of single-photon emission computed tomographic (SPECT) measures of [123I]beta-CIT binding to DA and 5-HT transporters with symptom severity in Parkinson's disease (PD). Forty-six L-dopa-responsive PD patients (Hoehn-Yahr stage 1-3) had SPECT scans at 20-24 h after injection of [123I]beta-CIT. Specific to nondisplaceable uptake ratios (designated V"3) were calculated in the striatum and hypothalamic/midbrain region, where the binding of [123I]beta-CIT is associated primarily with DA and 5-HT transporters, respectively. Striatal V"3 was significantly correlated with Hoehn-Yahr stage and total, motor and activities of daily living scores of Unified Parkinson's Disease Rating Scale (UPDRS). There was a significant correlation between the sum of lateralizing motor UPDRS subscores (tremor, rigidity, bradykinesia) calculated for each side of limbs and V"3 values in the contralateral striatum. No significant correlation was found between striatal V"3 and UPDRS rating of mentation, behavior, and mood. Hypothalamic/midbrain V"3 was not significantly correlated with either Hoehn-Yahr stage or UPDRS scores including both motor and nonmotor measures. The significant correlation of SPECT measures of striatal [123I]beta-CIT binding with motor severity suggests that [123I]beta-CIT binding to striatal DA transporters can serve as an in vivo indicator of disease severity in PD, with potential utility in the serial monitoring of disease progression.     

Sustained clinical improvement of Parkinson’s disease in two patients with facially-transplanted adipose-derived stromal vascular fraction cells

Cell-based therapy has been studied as an alternative for Parkinson's Disease (PD), with different routes of administration. The superficial fascia and facial muscles possess a rich blood supply, while venous and lymphatic access via the orbit and the cribriform plate provide a route to cerebral circulation. We here document positive clinical effects in two patients with PD treated with autologous adipose-derived stromal vascular fraction (SVF) cell preparation, implanted into the face and nasal cavity. Two patients with PD were transplanted with 60 million total nucleated cells in processed SVF into the facial muscles and nose. Serial evaluations were carried out up to 5 years (patient 1) and 1 year (patient 2), using the PDQ-39, the UPDRS, and serial videos. Video scoring was reviewed in a blinded fashion. Both patients reported qualitative improvement in motor and nonmotor symptoms following injection. Quantitatively, PDQ-39 scores decreased in all categories for both. On-medication UPDRS motor scores decreased in both (20 to 4 in patient 1, 18 to 3 in patient 2) despite taking the same or less medication (LEDD 350 to 350 in patient 1, LEDD 1175 to 400 in pt2). Both subjects had off-medication UPDRS scores similar to their pretreatment on-medication scores (20 to 14 in patient 1, 18 to 23 in patient 2). These preliminary findings describe local facial and nasal injections of SVF preparation followed by prolonged clinical benefit in two patients. Despite an unknown mechanism of action, this potential therapy warrants careful verification and investigation.     

Comorbidity of the nonmotor symptoms of Parkinson's disease.

Many patients with Parkinson's disease (PD) have clinically significant anxiety, depression, fatigue, sleep disturbance, or sensory symptoms. The comorbidity of these nonmotor symptoms and their relationship to PD severity has not been extensively evaluated. Ninety- nine nondemented PD patients were evaluated with the following battery of tests: Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Fatigue Severity Scale (FSS), Pittsburgh Sleep Quality Index (PSQI), a sensory symptom questionnaire, Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn & Yahr (H/Y) Stage, and the Schwab & England ADL scale (S/E). The comorbidity of the nonmotor symptoms and their relationship to PD severity was analyzed. Thirty-six percent of the study population had depression (BDI > or =10), 33% had anxiety (BAI > or =10), 40% had fatigue (FSS > 4), 47% had sleep disturbance (PSQI > 5), and 63% reported sensory symptoms. Only 12% of the sample had no nonmotor symptoms. Fifty-nine percent of the patients had two or more nonmotor symptoms, and nearly 25% had four or more. Increased comorbidity was associated with greater PD severity (P < 001). This study reveals that the nonmotor symptoms of PD frequently occur together in the same patients. Increased comorbidity of the five nonmotor symptoms was associated with greater PD severity. These results suggest that recognition of these diverse nonmotor symptoms may be enhanced by looking for others when one nonmotor symptom has been identified.     

Impact of the motor complications of Parkinson's disease on the quality of life.

The impact of motor complications of Parkinson's disease (PD), especially levodopa-induced dyskinesias, on quality of life (QL) was studied in 143 patients with PD. All were evaluated on the Hoehn and Yahr (H&Y) scale, and the Motor part of the Unified Parkinson's Disease Rating Scale (UPDRS). Motor complications were analyzed using the UPDRS Parts IV(A) and IV(B) and the Abnormal Involuntary Movement Scale. A specific Parkinson's disease quality of life questionnaire (39-item version, PDQ-39) was used. Motor complications significantly worsened the PDQ-39 Summary Index (PDQ-SI) of patients with PD. The dimensions of Mobility, Activities of Daily Living, Stigma, and Communication were the most strongly affected. "Peak dose" dyskinesia decreased Mobility, Emotional Well-Being, and Cognition, whereas biphasic dyskinesia affected Mobility, Stigma, Communication, and Activities of Daily Living. Morning akinesia, end-of-dose fluctuations, and "unpredictable offs" decreased QL on the dimensions of Mobility, Activities of Daily Living, Stigma, and Communication. Nocturnal akinesia led to a deterioration of all dimensions of the PDQ-39. Thus, motor complications and especially nocturnal akinesia and biphasic dyskinesias worsened the QL of PD patients.     

Responsiveness of impairments and disabilities in Parkinson's disease

The objective of this study is to evaluate the responsiveness of items of the Activities of Daily Living (ADL) and Motor section of the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with Parkinson's Disease (PD). A standardized Response Mean (SRM) per item was calculated using data of four trials (n=376) that randomised patients with early PD to dopamine agonist (DA) monotherapy or placebo. In the ADL section, the SRMs ranged from -0.04 (no effect) to -0.50 (moderate effect). Hand functions were the most responsive ADL items with 'handwriting' showing the largest response. Self-assessed symptoms were the least responsive. In the Motor section, SRMs ranged from -0.09 to -0.60 with bradykinesia items showing the largest response, especially the item 'finger taps'. The tremor items showed the smallest response, however, rest tremor arms was much more responsive than rest tremor of the head and legs or postural tremor. SRMs in the placebo group ranged from 0.08 to -0.21 in the ADL section and from 0.03 to -0.35 in the Motor section. ADL and motor items have comparable and mostly small effect sizes. The most responsive items are in the ADL section hand functions and in the Motor section bradykinesia items. A more responsive ADL section would omit the self-assessed symptoms and the Motor section would retain only rest tremor arms of the tremor items.     

Cerebral cortical areas in which thickness correlates with severity of motor deficits of Parkinson’s disease

The pathology of Parkinson’s disease (PD) is not confined to the nigrostriatal dopaminergic pathway, but also involves widespread cerebral cortical areas. Such non-nigrostriatal lesions may contribute to disabling dopa-resistant parkinsonian motor deficits. We performed cortical thickness analysis to identify cerebral cortical brain areas in which thickness correlates with the severity of parkinsonian motor deficits. We performed T1-weighted brain magnetic resonance imaging studies in 142 PD patients. Motor scores on the Unified Parkinson’s Disease Rating Scale (UPDRS) were measured, and subscores were calculated for bradykinesia, rigidity, tremor, and axial motor deficits. Using FreeSurfer software, we studied cortical areas in which thickness correlates with disease duration or the severity of parkinsonian motor deficits. The cortical thickness of the parieto-temporal association cortex, including the inferior parietal and posterior parietal cortices, showed a negative correlation with disease duration, total UPDRS motor score, and UPDRS subscores for bradykinesia and axial motor deficits. We found no cortical areas in which thickness correlated with subscores for tremor and rigidity. In addition to nigrostriatal dopaminergic deficit, progressive thinning of the parieto-temporal sensory association cortices related to disease duration seems to be related in part to the exacerbation of bradykinesia and the axial motor symptoms of PD.     

Identification of motor and nonmotor wearing-off in Parkinson's disease: comparison of a patient questionnaire versus a clinician assessment.

This study compares the sensitivity of a Patient Questionnaire versus information gathered by clinicians at a routine clinic visit in recognizing symptoms of wearing-off in early Parkinson's disease (PD). This Patient Questionnaire, containing 32 items representing a wide spectrum of motor and nonmotor wearing-off symptoms, was administered to subjects attending two PD clinics. The Patient Questionnaire results were compared to the information gathered by the clinician from the Unified Parkinson's Disease Rating Scale (UPDRS) Part IV, Question 36 and from a specific Clinical Assessment Question regarding loss of medication efficacy, wearing-off, sleepiness, dyskinesias, psychiatric complications, morning akinesia, other dopaminergic side effects, or none of the above. Examiners were blinded to study hypothesis and survey contents. Three hundred consecutive subjects with PD of <5 years duration were evaluated; the mean subject age was 72 +/- 9.6 years and 60.2% were men. Subjects reporting wearing-off were significantly younger (69.9 vs. 74.7 years) and differed regarding duration of PD symptoms (3.7 vs. 3.1 years). Wearing-off was found in 181 subjects (62.6%) by one or more of the three measures. The most sensitive tool was the Patient Questionnaire, with 165 subjects (57.1%) indicating symptoms of wearing-off. Question 36 of the UPDRS was positive in 127 subjects (43.9%), and the Clinical Assessment Question identified 85 subjects (29.4%) as experiencing wearing-off. All of these results were found to differ significantly. The mean number of wearing-off symptoms reported by the 165 subjects indicating wearing-off on the clinical survey was 6.25, with tremor being the most common motor feature and tiredness the most common nonmotor feature.     

Long-term effects of bilateral subthalamic nucleus stimulation on health-related quality of life in advanced Parkinson's disease.

We evaluated the long-term effects of subthalamic nucleus (STN) stimulation on health-related quality of life (HRQL) in patients with advanced Parkinson's disease (PD). STN stimulation improves motor function and decreases medication requirements in patients with advanced PD. The impact of STN stimulation on HRQL is less well established, especially beyond 1 year after surgery. We report HRQL outcomes for 18 patients with advanced PD. Patients were evaluated with the Parkinson's Disease Questionnaire-39 (PDQ-39), the Medical Outcome Study Short Form (SF-36), and the EuroQol visual analogue scale (VAS) before surgery, 6 months postoperatively, and at a long-term follow-up visit (mean, 35.9 months; range, 18-57 months after surgery). Preoperative scores on HRQL measures were compared to results obtained at short- and long-term follow-up evaluations. The VAS and all domains of the PDQ-39 except for cognition, communication, and social support showed marked improvements at 6 months after surgery. At the long-term follow-up, there were sustained improvements in the VAS (63% improvement; P = 0.0009) and in several domains of the PDQ-39 [mobility: 20%, P = 0.01; activities of daily living (ADL): 29%, P = 0.005; emotional well-being: 26%, P = 0.02; stigma: 43%, P = 0.003; and bodily discomfort: 35%, P = 0.007]. At the long-term evaluation, only the vitality domain of the SF-36 was significantly improved from baseline (16%; P = 0.01). In this selected group of patients, many of the short-term gains in HRQL persist beyond 18 months after STN implantation. Benefits in nonmotor aspects of HRQL such as bodily discomfort and stigma appear to be among the most durable.