Evaluation of timed tests in advanced Parkinsonian patients who were candidates for subthalamic stimulation

The evaluation of Parkinson disease relies on the use of clinical scales, mainly the UPDRS. However, especially for those candidates for functional surgery, other objective methods are also considered, including the use of timed tests. METHODS: The authors studied the motor performance of 33 patients with advanced Parkinson disease (PD) who were candidates for subthalamic nucleus (STN) stimulation. Presurgical motor evaluation included UPDRS and the 4 timed tests of the CAPIT protocol, including pronation-supination (PS), finger dexterity (FD), movement between 2 points (MTP), and the walking test (WT). A clinical evaluation was performed during patients' OFF condition and during their best ON state. Fifteen patients were implanted with STN stimulation and were evaluated at 6 months with the same protocol described for the presurgical evaluation. RESULTS: At baseline, all 4 timed tests significantly correlated with total and motor UPDRS scores, in the OFF and ON states, especially MTP. All timed tests, save WT, significantly improved after surgery in the OFF state (especially MTP; P = 0.002). After surgery, all timed tests, save FD, significantly correlated with total and motor UPDRS scores in the OFF state. Timed tests, especially MTP, maintained an excellent correlation with UPDRS in both OFF and ON states before and after surgery.     

Lack of motor symptoms progression in Parkinson's disease patients with long-term bilateral subthalamic deep brain stimulation

To evaluate the long-term progression of motor symptoms in Parkinson's disease (PD) patients treated with subthalamic nucleus deep brain stimulation (STN-DBS), we retrospectively analyzed data from 50 PD patients with bilateral STN-DBS. Clinical records at baseline and at several yearly intervals were reviewed. The Unified Parkinson's Disease Rating scale (UPDRS) was performed preoperatively after withholding medications for at least 12 hr (OFF) and after taking the usual dose of levodopa. Postoperative evaluations were completed in four clinical states: OFF medications—stimulators OFF (OFF/OFF); OFF medications—stimulators ON; ON medications—stimulators OFF; and ON medications—stimulators ON. The UPDRS motor scores OFF/OFF were virtually unmodified up to 5 years when compared with preoperative OFF scores. There was no significant difference between OFF/OFF score variations from baseline in patients with shorter (<11 years) and longer PD duration at the time of surgery. No consistent deterioration from untreated baseline was noted for each UPDRS motor subscore (tremor, rigidity, bradykinesia, and axial). Untreated PD motor scores did not worsen over time in patients undergoing STN-DBS, suggesting that there is no progression of motor severity. These results could be explained either by a natural stabilization of PD motor symptoms after many years or neuroprotective properties of STN-DBS.     

Staged unilateral versus bilateral subthalamic nucleus stimulator implantation in Parkinson disease.

In 17 consecutive patients with Parkinson disease (PD), bilateral subthalamic nucleus (STN) stimulators were implanted during staged surgeries. The Unified Parkinson Disease Rating Scale (UPDRS) and the Dyskinesia Disability Scale were completed both off and on medication prior to any surgery and also OFF and ON stimulation after each surgery. On-medication UPDRS activities of daily living (ADL) and motor examination scores changed little with unilateral or bilateral stimulation. Off-medication UPDRS motor examination scores improved to similar degrees after each staged STN electrode implantation. Most of the improvements in off-medication ADL scores, dyskinesia scores, complications of therapy, and medication dose reduction occurred after unilateral STN stimulation with smaller improvements after the second operation.     

Expectation and the placebo effect in Parkinson's disease patients with subthalamic nucleus deep brain stimulation.

To determine whether the degree to which a patient with Parkinson's disease expects therapeutic benefit from subthalamic nucleus-deep brain stimulation (STN-DBS) influences the magnitude of his or her improved motor response, 10 patients with idiopathic Parkinson's and bilateral STN-DBS were tested after a 12-hour period off medication and stimulation. Four consecutive UPDRS III scores were performed in the following conditions: (a) stimulation OFF, patient aware; (b) stimulation OFF, patient blind; (c) stimulation ON, patient aware; and (d) stimulation ON, patient blind. Statistical significance (P = 0.0001) was observed when comparing main effect ON versus OFF (mean ON: 32.55; mean OFF: 49.15). When the stimulation was OFF, patients aware of this condition had higher UPDRS motor scores than when they were blinded (mean: 50.7 vs. 47.6). With the stimulation ON, UPDRS motor scores were lower when the patients were aware of the stimulation compared with when they were blinded (mean: 30.6 vs. 34.5). The interaction between these levels was significant (P = 0.049). This variation was important for bradykinesia and was not significant for tremor and rigidity. The authors conclude that the information about the condition of the stimulation enhanced the final clinical effect in opposite directions. The results presented support the role of expectation and placebo effects in STN-DBS in Parkinson's disease patients.     

Bilateral subthalamic nucleus stimulation after bilateral pallidotomies in a patient with advanced Parkinson's disease

A 54-year-old man with advanced Parkinson's disease (PD) presented to our institution in early 2000. He had undergone a right pallidotomy in 1994, a left pallidotomy in 1996, and bilateral subthalamic nucleus (STN) electrode implants in 1999. The patient had cervical myelopathy for which he had undergone neck surgery in 1998. We used the Unified Parkinson's Disease Rating Scale (UPDRS) to evaluate motor performance in four states: combinations of stimulation OFF or ON and medication OFF or ON. There was no significant change in motor UPDRS scores with STN stimulation or with medications. Multiple attempts to optimize stimulation parameters and medication dosages did not result in significant and sustained improvement in activities of daily living or motor performance. To our knowledge, this is the first reported case of bilateral STN stimulation after bilateral pallidotomies. The presence of cervical myelopathy and the limited response to anti-Parkinson medications in this patient underscores the importance of patient selection for functional neurosurgery in PD.     

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.     

影响帕金森病患者生活质量的相关因素和分析

目的：研究影响帕金森病（PD）患者生活质量的相关因素。方法：对92例门诊PD患者，采用PDQ-39、UPDRS Ⅰ-Ⅳ、H＆Y、SE、MMSE、HAMD（17项）和HAMA（14项）分别进行评定，并进行统计学分析。结果：PDQ39（PDQ运动能力、PDQ日常生活、PDQ情绪健康、PDQ耻辱感及PDQ社会支持）、UPDRS（Ⅱ和Ⅲ）、医药费用支出、抑郁和焦虑情绪、认知水平以及左旋多巴每日剂量等均是影响生活质量的主要因素。同时女性比男性更易有耻辱感；〈55岁和〉65岁的患者的生活质量更差。结论：运用药物改善PD患者的运动障碍是提高生活质量的重要前提，但同时还要关注患者的情绪、社会功能等情况，尤其对女性、年龄〉55岁和〈65岁的患者。     

双侧丘脑底核电刺激对帕金森病患者生活质量影响的研究

目的对给予丘脑底核(STN)电刺激治疗的帕金森病(PD)患者进行生活质量评估,以评价治疗的有效性及不同因素对生活质量的影响。方法41例接受双侧STN深部电刺激(DBS)治疗的PD患者分别于术前及术后12个月应用统一帕金森病评定量表(UPDRS)、Hoehn和Yahr分期、Schwab和England日常生活活动量表、医院焦虑和抑郁量表(HADS)评价其临床情况;帕金森病生活质量问卷(PDQ-39)评价生活质量,并对统计结果进行配对t检验和Spearman相关性检验。结果UPDRS评分中日常生活活动、运动检查、并发症均有明显改善(P<0.001),而精神、行为和情绪无明显改善。HADS量表结果显示患者的焦虑及抑郁评分均有明显改善(P<0.001)。PDQ-39评分中运动、日常生活活动、情绪状态、身体不适、总评分等项均有明显改善(P<0.001),羞耻感也有改善(P<0.05)。相关性检验的结果提示与PDQ-39总评分变化程度成相关性的因素依次为:UPDRS运动检查“关”期(P<0.001), Schwab和England日常生活活动量表“关”期(P<0.001),UPDRS日常生活活动“关”期(P<0.01),HADS-抑郁(P< 0.05)。结论脑深部电刺激能明显改善PD患者的生活质量。     

Validation of the French language version of the Parkinson's Disease Questionnaire - PDQ-39

After Alzheimer's disease, Parkinson's disease (PD) is the second most frequent degenerative disease of the central nervous system. The consequences of PD at the functional, social and emotional levels warrant a better understanding the patient's perceptions as measured using a specific instrument rather than restricting the medical approach to the clinical evaluation of the motor component. In 1996, we began implementation of a project to transculturally validate the single specific instrument that had been published and was available at that time: PDQ-39. The scale consists in a 39-item questionnaire enabling determination of an overall quality-of-life score and scores for 8 specific dimensions: mobility, activities of daily living, emotional well-being, stigma, social support, cognitions, communication and bodily discomfort. Eighty-nine patients taking part in an open-label study of the safety of a combination of pergolide and dopa therapy were included and followed up on D15 and after 8 weeks. The process of "Forward-Backward" translation, conducted in close liaison with the authors, enabled semantic and linguistic validation of the French language version. The content was validated by PD experts. At baseline, the patients presented quality-of-life scores that were particularly impaired for the dimensions exploring Mobility, Emotional well-being and Bodily discomfort. The main metric properties of the scale were confirmed. The PDQ-39 scores were closely correlated with the related concepts investigated by generic scale, SF-36. The PDQ-39 scores were correlated with the "Mental and Mood Status", "Everyday Activities" and "Motor Status" dimensions determined by the UPDRS. The reliability, expressed by Cronbach coefficients alpha, showed strong consistency of the instrument, very similar to the data for the original version. In contrast to what was observed with SF-36, the scale was particularly sensitive to clinical changes. The initial results make PDQ-39 a precious tool for the optimization of management of patients presenting with PD.     

Pallidotomy does not ameliorate abnormal intracortical inhibition in Parkinson’s disease

Motor cortex excitability was assessed in 12 patients with Parkinson’s disease (PD) using transcranial magnetic stimulation. Patients were studied when mobile and medicated (“ON”) and when immobile after medication withdrawal (“OFF”). Results were compared to eight age-matched and 11 young controls. Cortical excitability was assessed by measurement of resting motor threshold (RMT), intracortical inhibition and cortical silent period duration. In five patients, the studies included assessments following pallidotomy. Cortical excitability was abnormal in patients with PD with reduced RMT in “ON” and “OFF” states, and less effective intracortical inhibition. Pallidotomy did not affect cortical excitability in either “ON” or “OFF” states, indicating that enhanced motor cortex excitability in patients with PD is unaffected by pallidotomy despite clinical improvement in motor scores.     

Controlled trial on the effect of 10 days low‐frequency repetitive transcranial magnetic stimulation (rTMS) on motor signs in Parkinson's disease

We evaluated the effect of low‐frequency rTMS on motor signs in Parkinson's disease (PD), under a double‐blind placebo‐controlled trial design. PD patients were randomly assigned to received either real (n = 9) or sham (n = 9) rTMS for 10 days. Each session comprises two trains of 50 stimuli each delivered at 1 Hz and at 90% of daily rest motor threshold using a large circular coil over the vertex. The effect of the stimulation, delivered during the ON‐period, was evaluated during both ON and OFF periods. Tests were carried out before and after the stimulation period, and again 1 week after. The effect of the stimulation was evaluated through several gait variables (cadence, step amplitude, velocity, the CV_{stride‐time}, and the turn time), hand dexterity, and also the total and motor sections of the UPDRS. Only the total and motor section of the UPDRS and the turn time during gait were affected by the stimulation, the effect appearing during either ON or OFF evaluation, and most importantly, equally displayed in both real and sham group. The rest of the variables were not influenced. We conclude the protocol of stimulation used, different from most protocols that apply larger amount of stimuli, but very similar to some previously reported to have excellent results, has no therapeutic value and should be abandoned. This contrasts with the positive reported effects using higher frequency and focal coils. Our work also reinforces the need for sham stimulation when evaluating the therapeutic effect of rTMS. © 2010 Movement Disorder Society     

尾状核指数对帕金森病脑深部电刺激术疗效的影响

目的 探讨尾状核指数对帕金森病（PD）双侧苍白球内侧部（GPi）脑深部电刺激术（DBS）疗效的影响。方法 回顾性分析2018年8月至2020年12月双侧GPi-DBS治疗的36例PD的临床资料。术前应用MRI测量尾状核指数、Evans指数及第三脑室宽度。术前、术后6个月应用39项帕金森病问卷（PDQ-39）评分、统一帕金森病评定量表Ⅲ（UPDRS-Ⅲ）评分、左旋多巴等效日剂量（LEDD）评估疗效。根据术后6个月UPDRS-Ⅲ评分分为改善组（n=26）与恶化组（n=10）。结果 术后6个月,PDQ-39评分、UPDRS-Ⅲ评分、LEDD均明显降低（P<0.05）。恶化组尾状核指数、第三脑室宽度较改善组明显增大（P<0.05）,而Evans指数无明显变化（P>0.05）。多因素logistic回归分析显示尾状核指数≥0.16(OR=1.76;95%CI 1.09～3.18;P=0.017)是PD术后UPDRS-Ⅲ评分恶化的独立影响因素。结论 双侧GPi-DBs明显改善PD症状,尾状核指数可用于评估PD病人双侧GPi-DBS后运动功能。     

Pardoprunox as adjunct therapy to levodopa in patients with Parkinson's disease experiencing motor fluctuations: results of a double-blind, randomized, placebo-controlled, trial

AimsTo determine the efficacy and safety of pardoprunox in levodopa-treated patients with Parkinson’s disease (PD) experiencing motor fluctuations.MethodsPatients were randomized to pardoprunox (up to 42 mg/day, n = 150) or placebo (n = 144). Pardoprunox was titrated to an optimal dose over 7 weeks, followed by a 12-week stable dose period. The primary efficacy variable was the change from baseline to study endpoint in total daily OFF time, based on patient diaries. Secondary analyses included the change in ON time without troublesome dyskinesias, UPDRS-ADL + Motor ON, UPDRS-ADL OFF and PDQ-39. Subgroup analyses explored the impact of pardoprunox on dyskinesias (UPDRS items 32 + 33), depression (Hospital Anxiety Depression Scale) and pain (Visual Analogue Scale).ResultsPardoprunox significantly reduced OFF time versus placebo (?1.62 h/day versus ?0.92 h/day, respectively, p = 0.0215). Compared to placebo, pardoprunox improved ON time without troublesome dyskinesias (p = 0.0386), UPDRS-ADL + Motor ON (p = 0.0003), and UPDRS-ADL OFF (p < 0.0001), while no significant difference was observed on PDQ-39. A high drop-out rate due to adverse events (AEs) (pardoprunox, 37%; placebo, 12%) suggested that the selected dose range may have been too high, and/or titration was too rapid.ConclusionsPardoprunox decreased OFF time and increased ON time without troublesome dyskinesias in levodopa-treated PD patients. The high drop-out rate at the selected doses justifies the investigation of lower doses. The impact of pardoprunox on dyskinesias and non-motor symptoms deserves further investigation.     

Differential effects of dopaminergic medication on basic motor performance and executive functions in Parkinson's disease

BackgroundPatients with Parkinson's disease (PD) often show deficits in the self-initiation and selection of movements, which can be partly compensated for by external cues. We here investigated impairments in the initiation and selection of self-initiated or externally cued movements in PD. Specifically, we assessed how behavioral changes relate to medication, disease severity, and basic motor or cognitive deficits.MethodsSeventeen akinetic-rigid PD patients and 16 healthy controls (HC) performed a computerized motor task assessing differences between internally and externally triggered movements and reaction times. Patients performed the task twice in a randomized fashion, once with their regular dopaminergic medication and once 12 h after withdrawal of medication. Additionally, all subjects underwent comprehensive neuropsychological and motor assessments.ResultsCompared to HC, patients showed a significant slowing across all tasks. Furthermore, patients showed a selective deficit of movement initiation as indexed by longer reaction times when movement lateralization was internally chosen as opposed to being externally cued. This deficit correlated significantly with motor scores of the Unified Parkinson's Disease Rating Scale (UPDRS). Notably, there was no main effect of dopaminergic medication (“ON”/”OFF”) on internally and externally triggered movements despite significant improvement of UPDRS and maximum finger tapping frequency in the “ON” state.DiscussionOur results suggest that disease severity in PD patients is related to disturbances in internal action initiation, selection and simple decision processes. Moreover, the data add further support to the notion that dopaminergic medication differentially affects motor and cognitive performance in PD. These findings imply that disturbances in executive functions in PD are also influenced by factors other than reduced dopaminergic activity.     

Orodispersible sublingual piribedil to abort OFF episodes: A single dose placebo‐controlled,randomized, double‐blind,cross‐over study

S90049, a novel sublingual formulation of the non‐ergoline D₂‐D₃ agonist piribedil, has a pharmacokinetic profile promising to provide rapid relief on motor signs in Parkinson's disease (PD). We assessed the efficacy and safety of S90049 in aborting OFF episodes responding to subcutaneous apomorphine in PD patients with motor fluctuations. This was a single‐dose double‐blind double‐placebo 3 × 3 cross‐over study. Optimal tested doses were determined during a previous open‐label titration phase (S90049 median dose: 60 mg, apomorphine: 5 mg). Primary endpoint was the maximal change versus baseline in UPDRS motor score (ΔUPDRS III) assessed after drug administration following an overnight withdrawal of antiparkinsonian medications. Thirty patients (age: 60 ± 8 years, PD duration: 12 ± 6 years, UPDRS III OFF: 37 ± 15) participated. S90049 wassuperior to placebo on ΔUPDRS III (?13 ± 12 versus ?7 ± 9 respectively; estimated difference ?5.2, 95% Confidence Interval (CI)[?10.4;0.05], P = 0.05). This was also true for secondary outcomes: number of patients switching from OFF to ON (17 on S90049 vs. 8 on placebo, P = 0.03), time to turn ON (P = 0.013) and duration of the ON phase (P = 0.03). In the 17 patients who switched ON on S90049, ΔUPDRS III was similar on S90049 (?21.2 ± 10.1) and apomorphine (?23.6 ± 14.1) (estimated difference: 4.0 95% CI [?2.9;10.9]). S90049 was well tolerated: no serious or unexpected adverse event occurred. A single dose of up to 60 mg of S90049 given sublingually was superior to placebo in improving UPDRS III and aborting a practical OFF in patients with advanced PD. Testing greater doses might improve response rate. © 2009 Movement Disorder Society     

Effects of medication and subthalamic nucleus deep brain stimulation on tongue movements in speakers with Parkinson's disease using electropalatography: a pilot study

Parkinson's disease (PD) affects speech in the majority of patients. Subthalamic nucleus deep brain stimulation (STN-DBS) is particularly effective in reducing tremor and rigidity. However, its effect on speech is variable. The aim of this pilot study was to quantify the effects of bilateral STN-DBS and medication on articulation, using electropalatography (EPG). Two patients, PT1 and PT2, were studied under four conditions: on and off medication and ON and OFF stimulation. The EPG protocol consisted of a number of target words with alveolar and velar stops, repeated 10 times in random order. The motor part III of the Unified Parkinson Disease Rating Scale (UPDRS) indicated significantly improved motor scores in the ON stimulation condition in both patients. However, PT1's articulation patterns deteriorated with stimulation whereas PT2 showed improving articulatory accuracy in the same condition. The results revealed different effects of stimulation and medication on articulation particularly with regard to timing. The study quantified less articulatory undershoot for velar stops in comparison to alveolars. Furthermore, the findings provided preliminary evidence that stimulation with medication has a more detrimental effect on articulation than stimulation without medication.     

Quality of Life and Motor Outcomes in Patients With Parkinson’s Disease 12 Months After Deep Brain Stimulation in China

BackgroundLong-term levodopa use is frequently associated with fluctuations in motor response and can have a serious adverse effect on the quality of life (QoL) of patients with Parkinson’s disease (PD). Deep brain stimulation (DBS) is effective in improving symptoms of diminished levodopa responsiveness. QoL improvements with DBS have been shown in several randomized control trials, mostly in Europe and the United States; however, there is a need for evidence from regions around the world.ObjectiveThe study aimed to demonstrate improvement in PD-related QoL in patients undergoing DBS in a prospective, multicenter study conducted in China.Materials and MethodsTo evaluate the effect of neurostimulation on the QoL of patients with PD, a Parkinson’s Disease Questionnaire (PDQ-8); Unified Parkinson’s Disease Rating Scale (UPDRS) I, II, III, and IV; and EuroQol 5-dimension questionnaire (EQ-5D) were administered at baseline and 12 months after DBS implantation. The mean change and percent change from baseline were reported for these clinical outcomes.ResultsAssessments were completed for 85 of the 89 implanted patients. DBS substantially improved patients’ QoL and function. Implanted patients showed statistically significant mean improvement in PDQ-8 and UPDRS III (on stimulation/off medication). In the patients who completed the 12-month follow-up visit, the percent change was ?22.2% for PDQ-8 and ?51.6% for UPDRS III (on stimulation/off medication). Percent change from baseline to 12 months for UPDRS I, II, III, and IV and EQ-5D were ?16.8%, ?39.4%, ?18.5%, and ?50.0% and 22.7%, respectively. The overall rate of incidence for adverse events was low at 15.7%. Favorable outcomes were also reported based on patient opinion; 95.3% were satisfied with DBS results.ConclusionsThese data were comparable to other studies around the world and showed alignment with the ability of DBS to meaningfully improve the QoL of patients with PD. More studies investigating DBS therapy for patients with PD are necessary to accurately characterize clinical outcomes for the global PD population.Clinical Trial RegistrationThe ClinicalTrials.gov registration number for this study is NCT02937688.     

Unilateral subthalamic nucleus deep brain stimulation contralateral to thalamic stimulation in Parkinson disease

The effects of unilateral subthalamic nucleus (STN) stimulation contralateral to thalamic stimulation in Parkinson disease (PD) have not been previously reported. We are reporting a patient who developed left arm tremor in 1994, at age 62, as her first PD symptom. She underwent right thalamic DBS surgery in 1999 that resulted in complete resolution of left arm tremor. Her PD symptoms progressed and she developed severe motor fluctuations and disabling dyskinesias. In 2003, she underwent left STN electrode implantation. Left STN stimulation improved contralateral motor scores in the medication OFF state, and allowed for reduced medication doses and less dyskinesia. However, there was no significant improvement in activities of daily living (ADL), motor scores in the medication ON state, gait, or postural stability.     

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.     

The impact of dopaminergic treatment over cognitive networks in Parkinson's disease: Stemming the tide?

Dopamine‐replacing therapies are an effective treatment for the motor aspects of Parkinson''s disease. However, its precise effect over the cognitive resting‐state networks is not clear; whether dopaminergic treatment normalizes their functional connectivity‐as in other networks‐ and the links with cognitive decline are presently unknown. We recruited 35 nondemented PD patients and 16 age‐matched controls. Clinical and neuropsychological assessments were performed at baseline, and conversion to dementia was assessed in a 10 year follow‐up. Structural and functional brain imaging were acquired in both the ON and practical OFF conditions. We assessed functional connectivity in both medication states compared to healthy controls, connectivity differences within participants related to the ON/OFF condition, and baseline connectivity of PD participants that converted to dementia compared to those who did not convert. PD participants showed and increased frontoparietal connectivity compared to controls: a pattern of higher connectivity between salience (SN) and default‐mode (DMN) networks both in the ON and OFF states. Within PD patients, this higher SN‐DMN connectivity characterized the participants in the ON state, while within‐DMN connectivity prevailed in the OFF state. Interestingly, participants who converted to dementia also showed higher SN‐DMN connectivity in their baseline ON scans compared to nonconverters. To conclude, PD patients showed higher frontoparietal connectivity in cognitive networks compared to healthy controls, irrespective of medication status, but dopaminergic treatment specifically promoted SN‐DM hyperconnectivity.