73 results found
Cury RG, Pavese N, Aziz TZ, et al., 2022, Gaps and roadmap of novel neuromodulation targets for treatment of gait in Parkinson’s disease, npj Parkinson's Disease, Vol: 8, Pages: 1-10, ISSN: 2373-8057
Gait issues in Parkinson’s disease (PD) are common and can be highly disabling. Although levodopa and deep brain stimulation (DBS) of the subthalamic nucleus and the globus pallidus internus have been established therapies for addressing the motor symptoms of PD, their effects on gait are less predictable and not well sustained with disease progression. Given the high prevalence of gait impairment in PD and the limitations in currently approved therapies, there has been considerable interest in alternative neuromodulation targets and techniques. These have included DBS of pedunculopontine nucleus and substantia nigra pars reticulata, spinal cord stimulation, non-invasive modulation of cortical regions and, more recently, vagus nerve stimulation. However, successes and failures have also emerged with these approaches. Current gaps and controversies are related to patient selection, optimal electrode placement within the target, placebo effects and the optimal programming parameters. Additionally, recent advances in pathophysiology of oscillation dynamics have driven new models of closed-loop DBS systems that may or may not be applicable to gait issues. Our aim is to describe approaches, especially neuromodulation procedures, and emerging challenges to address PD gait issues beyond subthalamic nucleus and the globus pallidus internus stimulation.
Mahmud M, Hadi Z, Prendergast M, et al., 2022, The effect of galvanic vestibular stimulation on postural balance in Parkinson's disease: a systematic review and meta-analysis, Journal of the Neurological Sciences, Vol: 442, Pages: 1-10, ISSN: 0022-510X
People with Parkinson's disease (PD) develop postural imbalance and falls. Galvanic Vestibular Stimulation (GVS) may potentially improve postural balance in humans and hence reduce falls in PD. This systematic review and meta-analysis investigate the effects of GVS on postural balance in PD.Six separate databases and research registers were searched for cross-over design trials that evaluated the effects of GVS on postural balance in PD. We used standardized mean difference (Hedges' g) as a measure of effect size in all studies.We screened 223 studies, evaluated 14, of which five qualified for the meta-analysis. Among n = 40 patients in five studies (range n = 5 to 13), using a fixed effects model we found an effect size estimate of g = 0.43 (p < 0.001, 95% CI [0.29,0.57]). However, the test for residual heterogeneity was significant (p < 0.001), thus we used a random effects model and found a pooled effect size estimate of 0.62 (p > 0.05, 95% CI [− 0.17, 1.41], I2 = 96.21%). Egger's test was not significant and thus trim and funnel plot indicated no bias. To reduce heterogeneity, we performed sensitivity analysis and by removing one outlier study (n = 7 patients), we found an effect size estimate of 0.16 (p < 0.05, 95% CI [0.01, 0.31], I2 = 0%).Our meta-analysis found GVS has a favourable effect on postural balance in PD patients, but due to limited literature and inconsistent methodologies, this favourable effect must be interpreted with caution.
Jesuthasan A, McColgan P, Sharma R, et al., 2022, Anti-amphiphysin associated paraneoplastic diencephalitis secondary to a thymic neuroendocrine tumour, NEUROLOGICAL SCIENCES, ISSN: 1590-1874
Hvingelby VS, Højholt Terkelsen M, Johnsen EL, et al., 2022, Spinal cord stimulation therapy for patients with Parkinson’s disease and gait problems (STEP-PD): study protocol for an exploratory, double-blind, randomised, placebo-controlled feasibility trial, BMJ Neurology Open, Vol: 4, Pages: e000333-e000333, ISSN: 2632-6140
Introduction Gait difficulties are common in Parkinson’s disease (PD) and cause significant disability. These symptoms are often resistant to treatment. Spinal cord stimulation (SCS) has been found to improve gait, including freezing of gait, in a small number of patients with PD. The mechanism of action is unclear, and some patients are non-responders. With this double-blind, placebo-controlled efficacy and feasibility clinical and imaging study, we aim to shed light on the mechanism of action of SCS and collect data to inform development of a scientifically sound clinical trial protocol. We also aim to identify clinical and imaging biomarkers at baseline that could be predictive of a favourable or a negative outcome of SCS and improve patient selection.Methods and analysis A total of 14 patients will be assessed with clinical rating scales and gait evaluations at baseline, and at 6 and 12 months after SCS implantation. They will also receive serial 18F-deoxyglucose and 18FEOBV PET scans to assess the effects of SCS on cortical/subcortical activity and brain cholinergic function. The first two patients will be included in an open pilot study while the rest will be randomised to receive active treatment or placebo (no stimulation) for 6 months. From this point, the entire cohort will enter an open label active treatment phase for a subsequent 6 months.Ethics and dissemination This study was reviewed and approved by the Committee on Health Research Ethics, Central Denmark RM. It is funded by the Danish Council for Independent Research. Independent of outcome, the results will be published in peer-reviewed journals and presented at national and international conferences.Trial registration number NCT05110053; ClinicalTrials.gov Identifier.
Bukhari SA, Nudelman KNH, Rumbaugh M, et al., 2022, Parkinson's Progression Markers Initiative brain autopsy program, Parkinsonism & Related Disorders, Vol: 101, Pages: 62-65, ISSN: 1353-8020
Hvingelby V, Glud A, Sorensen J, et al., 2022, Interventions to Improve Gait in Parkinson's Disease: A Systematic Review and Network Meta-Analysis, Publisher: WILEY, Pages: 243-244, ISSN: 1351-5101
Hvingelby VS, Glud AN, Sorensen JCH, et al., 2022, Interventions to improve gait in Parkinson's disease: a systematic review of randomized controlled trials and network meta-analysis, JOURNAL OF NEUROLOGY, Vol: 269, Pages: 4068-4079, ISSN: 0340-5354
Mahmud M, Hadi Z, Prendergast M, et al., 2022, The effect of galvanic vestibular stimulation on postural balance in Parkinson’s Disease: A systematic review and meta-analysis, Publisher: Cold Spring Harbor Laboratory
People with Parkinson’s disease (PD) experience postural imbalance, leading to considerably increased risk of falls. Galvanic Vestibular Stimulation (GVS) is postulated to modulate postural balance in humans and improve it in PD. This systematic review and meta-analysis investigate the effects of GVS on postural balance in PD. Six separate databases and research registers were searched for cross-over design trials that evaluated the effects of GVS on postural balance in PD. We used standardized mean difference (Hedges’ g) as a measure of effect size in all studies. We screened 223 studies, evaluated 14, of which five qualified for the meta-analysis. Among n = 40 patients in five studies (range n= 5 to 13), using a fixed effects model we found an effect size estimate of g = 0.43 (p < 0.001, 95% CI [0.29,0.57]). However, the test for residual heterogeneity was significant (p < 0.001), thus we used a random effects model and found a pooled effect size estimate of 0.62 (p > 0.05, 95% CI [– 0.17, 1.41], I2 = 96.21%). Egger’s test was not significant and thus trim and funnel plot indicated no bias. To reduce heterogeneity, we performed sensitivity analysis and by removing one outlier study (n = 7 patients), we found an effect size estimate of 0.16 (p < 0.05, 95% CI [0.01, 0.31], I2 = 0%). Our meta-analysis found GVS has a favourable effect on postural balance in PD patients, but due to limited literature and inconsistent methodologies, this favourable effect must be interpreted with caution.
Jameel A, Gedroyc W, Nandi D, et al., 2021, Double lesion MRgFUS treatment of essential tremor targeting the thalamus and posterior sub-thalamic area: preliminary study with two year follow-up, British Journal of Neurosurgery, Vol: 36, Pages: 241-250, ISSN: 0268-8697
BackgroundMR-guided focused ultrasound (MRgFUS) is an effective treatment for essential tremor (ET). However, the optimal intracranial target sites remain to be determined.ObjectiveTo assess MRgFUS induced sequential lesions in (anterior-VIM/VOP nuclei) the thalamus and then posterior subthalamic area (PSA) performed during the same procedure for alleviating ET.Methods14 patients had unilateral MRgFUS lesions placed in anterior-VIM/VOP then PSA. Bain-Findley Spirals were collected during MRgFUS from the treated arm (BFS-TA) and throughout the study from the treated (BFS-TA) and non-treated (BFS-NTA) arms and scored by blinded assessors. Although, the primary outcome was change in the BFS-TA from baseline to 12 months we have highlighted the 24-month data. Secondary outcomes included the Clinical Rating Scale for Tremor (CRST), Quality of Life for ET (QUEST) and PHQ-9 depression scores.ResultsThe mean improvement in the BFS-TA from baseline to 24 months was 41.1% (p < 0.001) whilst BFS-NTA worsened by 8.8% (p < 0.001). Intra-operative BFS scores from the targeted arm showed a mean 27.9% (p < 0.001) decrease after anterior-VIM/VOP ablation and an additional 30.1% (p < 0.001) reduction from post anterior-VIM/VOP to post-PSA ablation. Mean improvements at 24 month follow-up in the CRST-parts A, B and C were 60.7%, 30.4% and 65.6% respectively and 37.8% in QUEST-tremor score (all p < 0.05). Unilateral tremor severity scores decreased in the treated arm (UETTS-TA) 72.9% (p = 0.001) and non-treated arm (UETTS-NTA) 30.5% (p = 0.003). At 24 months residual adverse effects were slight unsteadiness (n = 1) and mild hemi-chorea (n = 1).ConclusionUnilateral anterior-VIM/VOP and PSA MRgFUS significantly diminished contralateral arm tremor with improvements in arm function, tremor related disability and quality of life, with an acceptable adv
Alcalay RN, Wolf P, Chiang MSR, et al., 2020, Longitudinal measurements of glucocerebrosidase activity in Parkinson's patients, Annals of Clinical and Translational Neurology, Vol: 7, Pages: 1816-1830, ISSN: 2328-9503
ObjectiveReduction in glucocerebrosidase (GCase; encoded by GBA) enzymatic activity has been linked to Parkinson’s disease (PD). Here, we correlated GCase activity and PD phenotype in the Parkinson’s Progression Markers Initiative (PPMI) cohort.MethodsWe measured GCase activity in dried blood spots from 1559 samples of participants in the inception PPMI cohort, collected in four annual visits (from baseline visit to Year-3). Participants (PD, n = 392; controls, n = 175) were fully sequenced for GBA variants by means of genome-wide genotyping arrays, whole-exome sequencing, whole-genome sequencing, Sanger sequencing, and RNA-sequencing.ResultsFifty-two PD participants (13.4%) and 13 (7.4%) controls carried a GBA variant. GBA status was strongly associated with GCase activity. Among noncarriers, GCase activity was similar between PD and controls. Among GBA p.E326K carriers (PD, n = 20; controls, n = 5), activity was significantly lower in PD carriers than control carriers (9.53 µmol/L/h vs. 11.68 µmol/L/h, P = 0.035). Glucocerebrosidase activity was moderately (r = 0.45) associated with white blood cell (WBC) count. Next, we divided the noncarriers with PD to tertiles based on WBC count-corrected enzymatic activity. Members of the lower tertile had higher MDS-Unified Parkinson’s Disease Rating Scale motor score in the “off” medication examination at year-III exam. Longitudinal analyses demonstrated slight reduction of activity in samples collected earlier on in the study, likely because of longer storage time.InterpretationGCase activity is associated with GBA genotype, WBC count, and among p.E326K variant carriers, with PD status. Reduced activity may also be associated with worse phenotype but longer follow up is required to confirm this observation.
Ciocca M, Bocum A, Tai Y, 2020, "Motor" DDS: is motor sensitization underestimated after STN-DBS?, Movement-Disorder-Society (MDS) International Virtual Congress, Publisher: WILEY, Pages: S611-S611, ISSN: 0885-3185
Tai YF, 2020, Comment on: Management of Parkinson's Disease During Pregnancy, MOVEMENT DISORDERS CLINICAL PRACTICE, Vol: 7, Pages: 881-881, ISSN: 2330-1619
Huo W, Angeles P, Tai YF, et al., 2020, A heterogeneous sensing suite for multisymptom quantification of Parkinson’s disease, IEEE Transactions on Neural Systems and Rehabilitation Engineering, Vol: 28, Pages: 1397-1406, ISSN: 1534-4320
Parkinson’s disease (PD) is the second most common neurodegenerative disease affecting millions worldwide. Bespoke subject-specific treatment (medication or deep brain stimulation (DBS)) is critical for management, yet depends on precise assessment cardinal PD symptoms - bradykinesia, rigidity and tremor. Clinician diagnosis is the basis of treatment, yet it allows only a cross-sectional assessment of symptoms which can vary on an hourly basis and is liable to inter- and intra-rater subjectivity across human examiners. Automated symptomatic assessment has attracted significant interest to optimise treatment regimens between clinician visits, however, no wearable has the capacity to simultaneously assess all three cardinal symptoms. Challenges in the measurement of rigidity, mapping muscle activity outof-clinic and sensor fusion have inhibited translation. In this study, we address all through a novel wearable sensor system and learning algorithms. The sensor system is composed of a force-sensor, two inertial measurement units (IMUs) and four custom mechanomyography (MMG) sensors. The system was tested in its capacity to predict Unified Parkinson’s Disease Rating Scale (UPDRS) scores based on quantitative assessment of bradykinesia, rigidity and tremor in PD patients. 23 PD patients were tested with the sensor system in parallel with exams conducted by treating clinicians and 10 healthy subjects were recruited as a comparison control group. Results prove the system accurately predicts UPDRS scores for all symptoms (85.4% match on average with physician assessment) and discriminates between healthy subjects and PD patients (96.6% on average). MMG features can also be used for remote monitoring of severity and fluctuations in PD symptoms out-of-clinic. This closedloop feedback system enables individually tailored and regularly updated treatment, facilitating better outcomes for a very large patient population.
Reichmann H, Lees A, Rocha J-F, et al., 2020, Effectiveness and safety of opicapone in Parkinson's disease patients with motor fluctuations: the OPTIPARK open-label study, Translational Neurodegeneration, Vol: 9, Pages: 1-9, ISSN: 2047-9158
BackgroundThe efficacy and safety of opicapone, a once-daily catechol-O-methyltransferase inhibitor, have been established in two large randomized, placebo-controlled, multinational pivotal trials. Still, clinical evidence from routine practice is needed to complement the data from the pivotal trials.MethodsOPTIPARK (NCT02847442) was a prospective, open-label, single-arm trial conducted in Germany and the UK under clinical practice conditions. Patients with Parkinson’s disease and motor fluctuations were treated with opicapone 50 mg for 3 (Germany) or 6 (UK) months in addition to their current levodopa and other antiparkinsonian treatments. The primary endpoint was the Clinician’s Global Impression of Change (CGI-C) after 3 months. Secondary assessments included Patient Global Impressions of Change (PGI-C), the Unified Parkinson’s Disease Rating Scale (UPDRS), Parkinson’s Disease Questionnaire (PDQ-8), and the Non-Motor Symptoms Scale (NMSS). Safety assessments included evaluation of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs).ResultsOf the 506 patients enrolled, 495 (97.8%) took at least one dose of opicapone. Of these, 393 (79.4%) patients completed 3 months of treatment. Overall, 71.3 and 76.9% of patients experienced any improvement on CGI-C and PGI-C after 3 months, respectively (full analysis set). At 6 months, for UK subgroup only (n = 95), 85.3% of patients were judged by investigators as improved since commencing treatment. UPDRS scores at 3 months showed statistically significant improvements in activities of daily living during OFF (mean ± SD change from baseline: − 3.0 ± 4.6, p < 0.0001) and motor scores during ON (− 4.6 ± 8.1, p < 0.0001). The mean ± SD improvements of − 3.4 ±
Simuni T, Brumm MC, Uribe L, et al., 2020, Clinical and Dopamine Transporter Imaging Characteristics of Leucine- Rich Repeat Kinase 2 (LRRK2) and Glucosylceramidase Beta (GBA) Parkinson's Disease Participants in the Parkinson's Progression Markers Initiative: A Cross-Sectional Study, MOVEMENT DISORDERS, Vol: 35, Pages: 833-844, ISSN: 0885-3185
Simuni T, Uribe L, Cho HR, et al., 2020, Clinical and dopamine transporter imaging characteristics of non-manifest LRRK2 and GBA mutation carriers in the Parkinson's Progression Markers Initiative (PPMI): a cross-sectional study, LANCET NEUROLOGY, Vol: 19, Pages: 71-80, ISSN: 1474-4422
Chahine LM, Siderowf A, Barnes J, et al., 2019, Predicting progression in Parkinson's Disease using baseline and 1-Year change measures, Journal of Parkinsons Disease, Vol: 9, Pages: 665-679, ISSN: 1877-718X
Background:Improved prediction of Parkinson’s disease (PD) progression is needed to support clinical decision-making and to accelerate research trials.Objectives:To examine whether baseline measures and their 1-year change predict longer-term progression in early PD.Methods:Parkinson’s Progression Markers Initiative study data were used. Participants had disease duration ≤2 years, abnormal dopamine transporter (DAT) imaging, and were untreated with PD medications. Baseline and 1-year change in clinical, cerebrospinal fluid (CSF), and imaging measures were evaluated as candidate predictors of longer-term (up to 5 years) change in Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) score and DAT specific binding ratios (SBR) using linear mixed-effects models.Results:Among 413 PD participants, median follow-up was 5 years. Change in MDS-UPDRS from year-2 to last follow-up was associated with disease duration (β= 0.351; 95% CI = 0.146, 0.555), male gender (β= 3.090; 95% CI = 0.310, 5.869), and baseline (β= –0.199; 95% CI = –0.315, –0.082) and 1-year change (β= 0.540; 95% CI = 0.423, 0.658) in MDS-UPDRS; predictors in the model accounted for 17.6% of the variance in outcome. Predictors of percent change in mean SBR from year-2 to last follow-up included baseline rapid eye movement sleep behavior disorder score (β= –0.6229; 95% CI = –1.2910, 0.0452), baseline (β= 7.232; 95% CI = 2.268, 12.195) and 1-year change (β= 45.918; 95% CI = 35.994,55.843) in mean striatum SBR, and 1-year change in autonomic symptom score (β= –0.325;95% CI = –0.695, 0.045); predictors in the model accounted for 44.1% of the variance.Conclusions:Baseline clinical, CSF, and imaging measures in early PD predicted change in MDS-UPDRS and dopamine-transporter binding, but the predictive value of the models was low. Adding the short-term change of possible predictors improved
Pavese N, Tai YF, Yousif N, et al., 2019, Traditional trial-and-error versus neuroanatomical-3D-image software-assisted deep brain stimulation programming in patients with Parkinson's disease, World Neurosurgery, Vol: 134, Pages: e98-e102, ISSN: 1878-8750
BACKGROUND: Programming Deep Brain Stimulation (DBS) settings in patients with Parkinson's disease (PD) is challenging and time consuming due to the vast number of possible parameter combinations. This results in long sessions that can be exhausting for the patients and the physicians. GUIDETM (Boston Scientific) is a 3D-neuroantomical visual software that precisely visualises the location of the DBS electrode in the subthalamic nucleus (STN). OBJECTIVE: To compared the duration and clinical effects of traditional trial-and-error versus GUIDETM-assisted DBS programming in ten PD patients treated with STN DBS. METHODS: For each patient, neurostimulation parameters were selected with GUIDETM to create a stimulation field encompassing the dorsal part of the STN. On programming day, each patient was assessed with both traditional and GUIDETM approaches using a cross-over design. For GUIDETM-assisted session, the patients were programmed directly with the DBS settings obtained with the stimulated field model and, if necessary, parameters were adjusted to achieve optimal clinical response. Clinical improvement was assessed with UPDRS scores for limb bradykinesia, tremor, and rigidity. RESULTS: In seven patients, DBS settings obtained with GUIDETM led to a suboptimal clinical improvement and mild adjustments were required. After these adjustments, the magnitude of clinical improvement with the two approaches was comparable (p= 0.8219). Programming time with GUIDETM was significantly shorter than that traditional programming approach (p< 0.0001). CONCLUSIONS: Visualization of stimulation fields with GUIDETM provides useful information to achieve a clinical improvement comparable to that obtained with the traditional trial-and-error approach, but with shorter and more efficient programming sessions.
Arami A, Poulakakis-Daktylidis A, Tai YF, et al., 2019, Prediction of gait freezing in Parkinsonian patients: a binary classification augmented with time series prediction, IEEE Transactions on Neural Systems and Rehabilitation Engineering, Vol: 27, Pages: 1909-1919, ISSN: 1534-4320
This paper presents a novel technique to predict freezing of gait in advance-stage Parkinsonian patients using movement data from wearable sensors. A two-class approach is presented which consists of autoregressive predictive models to project the feature time series, followed by machine learning based classifiers to discriminate freezing from nonfreezing based on the predicted features. To implement and validate our technique a set of time domain and frequency domain features were extracted from the 3D acceleration data, which was then analyzed using information theoretic and feature selection approaches to determine the most discriminative features. Predictive models were trained to predict the features from their past values, then fed into binary classifiers based on support vector machines and probabilistic neural networks which were rigorously cross validated. We compared the results of this approach with a three-class classification approach proposed in previous literature, in which a pre-freezing class was introduced and the problem of prediction of the gait freezing incident was reduced to solving a three-class classification problem. The twoclass approach resulted in a sensitivity of 93±4%, specificity of 91±6%, with an expected prediction horizon of 1.72 seconds. Our subject-specific gait freezing prediction algorithm outperformed existing algorithms, yields consistent results across different subjects and is robust against the choice of classifier, with slight variations in the selected features. In addition, we analyzed the merits and limitations of different families of features to predict gait freezing.
Ghadery C, Best LA, Pavese N, et al., 2019, PET evaluation of microglial activation in non-neurodegenerative brain diseases, CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS, Vol: 19, Pages: 1-12, ISSN: 1528-4042
Eventide C, Nair A, Tai YF, et al., 2019, An unusual case of bilateral anterior opercular syndrome from a neuro-rehabilitation perspective, Journal of the American Academy of PAs
Colmenares L, Jones L, Tai YF, et al., 2019, Orthostatic tremor – a case series, International Congress of Parkinson's Disease and Movement Disorders 2019
Prakash N, Caspell-Garcia C, Coffey C, et al., 2019, Feasibility and safety of lumbar puncture in the Parkinson's disease research participants: Parkinson's Progression Marker Initiative (PPMI), PARKINSONISM & RELATED DISORDERS, Vol: 62, Pages: 201-209, ISSN: 1353-8020
Best L, Ghadery C, Pavese N, et al., 2019, New and Old TSPO PET Radioligands for Imaging Brain Microglial Activation in Neurodegenerative Disease, CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS, Vol: 19, ISSN: 1528-4042
Amara AW, Chahine L, Seedorff N, et al., 2019, Self-reported physical activity levels and clinical progression in early Parkinson's disease, PARKINSONISM & RELATED DISORDERS, Vol: 61, Pages: 118-125, ISSN: 1353-8020
Mousele C, Bentley P, Tai YF, 2018, A rare presentation of orthostatic tremor as abdominal tremor, Tremor and Other Hyperkinetic Movements, Vol: 8, ISSN: 2160-8288
Background: Orthostatic tremor (OT) is a weight-bearing hyperkinetic disorder characterized by unsteadiness while standing that is relieved when sitting or walking.Case report: A 66-year-old male presented with a 5 year-history of tremor in his abdomen, but only when he stood in a stationary position. The tremor disappeared when he stood or walked. On examination, he had palpable tremor in his rectus abdominis and gastrocnemius virtually instantaneously after standing. His electromyography findings confirmed the presence of a 12-Hz tremor in the tibialis anterior while standing, with subharmonics recorded in the external obliques and rectus abdominis.Discussion: Our case illustrates an unusual presentation of OT. The diagnosis is supported by its characteristic frequency and specific appearance only during upright stance.
Maxan A, Mason S, Saint-Pierre M, et al., 2018, Outcome of cell suspension allografts in a patient with Huntington's disease, Annals of Neurology, Vol: 84, Pages: 950-956, ISSN: 0364-5134
For patients with incurable neurodegenerative disorders such as Huntington's (HD) and Parkinson's disease, cell transplantation has been explored as a potential treatment option. Here, we present the first clinicopathological study of a patient with HD in receipt of cell-suspension striatal allografts who took part in the NEST-UK multicenter clinical transplantation trial. Using various immunohistochemical techniques, we found a discrepancy in the survival of grafted projection neurons with respect to grafted interneurons as well as major ongoing inflammatory and immune responses to the grafted tissue with evidence of mutant huntingtin aggregates within the transplant area. Our results indicate that grafts can survive more than a decade post-transplantation, but show compromised survival with inflammation and mutant protein being observed within the transplant site. Ann Neurol 2018; 1-7.
Marek K, Chowdhury S, Siderowf A, et al., 2018, The Parkinson's progression markers initiative (PPMI) - establishing a PD biomarker cohort, Annals of Clinical and Translational Neurology, Vol: 5, Pages: 1460-1477, ISSN: 2328-9503
ObjectiveThe Parkinson's Progression Markers Initiative (PPMI) is an observational, international study designed to establish biomarker-defined cohorts and identify clinical, imaging, genetic, and biospecimen Parkinson's disease (PD) progression markers to accelerate disease-modifying therapeutic trials.MethodsA total of 423 untreated PD, 196 Healthy Control (HC) and 64 SWEDD (scans without evidence of dopaminergic deficit) subjects were enrolled at 24 sites. To enroll PD subjects as early as possible following diagnosis, subjects were eligible with only asymmetric bradykinesia or tremor plus a dopamine transporter (DAT) binding deficit on SPECT imaging. Acquisition of data was standardized as detailed at www.ppmi-info.org.ResultsApproximately 9% of enrolled subjects had a single PD sign at baseline. DAT imaging excluded 16% of potential PD subjects with SWEDD. The total MDS-UPDRS for PD was 32.4 compared to 4.6 for HC and 28.2 for SWEDD. On average, PD subjects demonstrated 45% and 68% reduction in mean striatal and contralateral putamen Specific Binding Ratios (SBR), respectively. Cerebrospinal fluid (CSF) was acquired from >97% of all subjects. CSF (PD/HC/SWEDD pg/mL) α-synuclein (1845/2204/2141) was reduced in PD vs HC or SWEDD (P < 0.03). Similarly, t-tau (45/53) and p-tau (16/18) were reduced in PD versus HC (P < 0.01),InterpretationPPMI has detailed the biomarker signature for an early PD cohort defined by clinical features and imaging biomarkers. This strategy provides the framework to establish biomarker cohorts and to define longitudinal progression biomarkers to support future PD treatment trials.
Deuschl G, Jain R, Scholtes H, et al., 2018, Outcomes of a Prospective, Multicenter International Registry of Deep Brain Stimulation, 70th Annual Meeting of the American-Academy-of-Neurology (AAN), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0028-3878
Pavese N, Tai YF, 2018, Nigrosome imaging and neuromelanin sensitive MRI in diagnostic evaluation of parkinsonism, Movement Disorders Clinical Practice, ISSN: 2330-1619
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