Retinal layers in Parkinson's disease::A meta-analysis of spectral-domain optical coherence tomography studies

Background: Patients with Parkinson's disease experience visual symptoms, partially originating from retinal changes. Since 2011, multiple case-control studies using spectral-domain OCT, which allows for studying individual retinal layers, have been published. The aim of this study was to substantiate the occurrence, extent, and location of retinal degeneration in Parkinson's by meta-analysis. Methods: Spectral-domain OCT case-control data were collected by performing a search in PubMed and Embase with terms: “optical coherence tomography” and “parkinson”, up to November 5th, 2018. Studies with fewer than 10 patients or controls were excluded. We performed a random effects meta-analysis. Heterogeneity was evaluated with I2 statistics; publication bias with Egger's and Begg's tests. Results: Out of 77 identified studies, 36 were included, totaling 1916 patients and 2006 controls. A significant thinning of the peripapillary retinal nerve fiber layer (d = −0.42; 95% confidence interval −0.54 to −0.29) and the combined ganglion cell and inner plexiform layers (d = −0.40; −0.72, to −0.07) was found. The inner nuclear layer and outer plexiform layer did not show significant changes. Heterogeneity ranged from 3 to 92%; no publication bias was found. Conclusions: Parkinson's patients show significant thinning of the inner retinal layers, resembling changes found in glaucoma and other neurodegenerative diseases like Alzheimer's. Study of different cell layers in-vivo is possible by moving from time-to spectral domain OCT. Retinal degeneration may be affiliated with neurodegenerative pathology overall, and could serve as a biomarker in neurodegenerative disorders. Longitudinal research including clinical correlations is needed to determine usefulness in Parkinson's disease

Letter to the editor, "Validation and clinical value of the MANAGE-PD tool:A clinician-reported tool to identify Parkinson's disease patients inadequately controlled on oral medications"

The MANAGE-PD tool may help general neurologists in deciding whether a patient with advanced Parkinson's disease should be referred for an advanced therapy. Although the development and clinical validation of MANAGE-PD would appear to serve an important need, we urge the reader to be aware of several methodological concerns.</p

Treatment of subcutaneous nodules after infusion of apomorphine:a biopsy-controlled study comparing 4 frequently used therapies

This study aimed to provide clinical evidence for existing treatments of subcutaneous nodules after subcutaneous infusion of apomorphine, using a biopsy-controlled prospective crossover design of four treatments. We demonstrated that dilution of apomorphine significantly improved patient satisfaction, while subcutaneous hydrocortisone reduced nodule size, however with no differences in the histopathology

Electrical stimulation of the nucleus basalis of meynert:a systematic review of preclinical and clinical data

Deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) has been clinically investigated in Alzheimer's disease (AD) and Lewy body dementia (LBD). However, the clinical effects are highly variable, which questions the suggested basic principles underlying these clinical trials. Therefore, preclinical and clinical data on the design of NBM stimulation experiments and its effects on behavioral and neurophysiological aspects are systematically reviewed here. Animal studies have shown that electrical stimulation of the NBM enhanced cognition, increased the release of acetylcholine, enhanced cerebral blood flow, released several neuroprotective factors, and facilitates plasticity of cortical and subcortical receptive fields. However, the translation of these outcomes to current clinical practice is hampered by the fact that mainly animals with an intact NBM were used, whereas most animals were stimulated unilaterally, with different stimulation paradigms for only restricted timeframes. Future animal research has to refine the NBM stimulation methods, using partially lesioned NBM nuclei, to better resemble the clinical situation in AD, and LBD. More preclinical data on the effect of stimulation of lesioned NBM should be present, before DBS of the NBM in human is explored further

Systematic analysis of PINK1 variants of unknown significance shows intact mitophagy function for most variants

Pathogenic variants in PINK1 cause early-onset Parkinson’s disease. Although many PINK1 variants have been reported, the clinical significance is uncertain for the majority of them. To gain insights into the consequences of PINK1 missense variants in a systematic manner, we selected 50 PINK1 missense variants from patient- and population-wide databases and systematically classified them using Sherloc, a comprehensive framework for variant interpretation based on ACMG-AMP guidelines. We then performed functional experiments, including mitophagy and Parkin recruitment assays, to assess the downstream consequences of PINK1 variants. Analysis of PINK1 missense variants based on Sherloc showed that the patient databases over-annotate variants as likely pathogenic. Furthermore, our study shows that pathogenic PINK1 variants are most often linked to a loss-of-function for mitophagy and Parkin recruitment, while this is not observed for variants of unknown significance. In addition to the Sherloc framework, the added layer of evidence of our functional tests suggests a reclassification of 9/50 missense variants. In conclusion, we suggest the assessment of multiple layers of evidence, including functional data on top of available clinical and population-based data, to support the clinical classification of a variant and show that the presence of a missense variant in PINK1 in a Parkinson’s disease case does not automatically imply pathogenicity

Enhanced arm swing improves Parkinsonian gait with EEG power modulations resembling healthy gait

BACKGROUND: The supplementary motor area (SMA) is implicated in stereotypic multi-limb movements such as walking with arm swing. Gait difficulties in Parkinson's Disease (PD) include reduced arm swing, which is associated with reduced SMA activity. OBJECTIVE: To test whether enhanced arm swing improves Parkinsonian gait and explore the role of the SMA in such an improvement. METHODS: Cortical activity and gait characteristics were assessed by ambulant EEG, accelerometers and video recordings in 27 PD patients with self-reported gait difficulties and 35 healthy participants when walking normally. Within these two groups, 19 PD patients additionally walked with enhanced arm swing and 30 healthy participants walked without arm swing. Power changes across the EEG frequency spectrum were assessed by Event Related Spectral Perturbation analysis of recordings from Fz over the putative SMA and gait analysis was performed. RESULTS: Baseline PD gait, characterized by reduced arm swing among other features, exhibited reduced within-step Event Related Desynchronization (ERD)/Synchronization (ERS) alternation (Fz; 20-50Hz), accompanied by a reduced step length and walking speed. All became similar to normal gait when patients walked with enhanced arm swing. When healthy controls walked without arm swing, their alternating ERD-ERS pattern decreased, mimicking baseline PD gait. CONCLUSION: Enhanced arm swing may serve as a driving force to overcome impaired gait control in PD patients by restoring reduced ERD-ERS alternation over the putative SMA. Accompanied by increased step length and walking speed, this provides a neural underpinning of arm swing as an effective rehabilitation concept for improving Parkinsonian gait

A Method for Automatic and Objective Scoring of Bradykinesia Using Orientation Sensors and Classification Algorithms

Correct assessment of bradykinesia is a key element in the diagnosis and monitoring of Parkinson's disease. Its evaluation is based on a careful assessment of symptoms and it is quantified using rating scales, where the Movement Disorders Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is the gold standard. Regardless of their importance, the bradykinesia-related items show low agreement between different evaluators. In this study, we design an applicable tool that provides an objective quantification of bradykinesia and that evaluates all characteristics described in the MDS-UPDRS. Twenty-five patients with Parkinson's disease performed three of the five bradykinesia-related items of the MDS-UPDRS. Their movements were assessed by four evaluators and were recorded with a nine degrees-of-freedom sensor. Sensor fusion was employed to obtain a 3-D representation of movements. Based on the resulting signals, a set of features related to the characteristics described in the MDS-UPDRS was defined. Feature selection methods were employed to determine the most important features to quantify bradykinesia. The features selected were used to train support vector machine classifiers to obtain an automatic score of the movements of each patient. The best results were obtained when seven features were included in the classifiers. The classification errors for finger tapping, diadochokinesis and toe tapping were 15-16.5%, 9.3-9.8%, and 18.2-20.2% smaller than the average interrater scoring error, respectively. The introduction of objective scoring in the assessment of bradykinesia might eliminate inconsistencies within evaluators and interrater assessment disagreements and might improve the monitoring of movement disorders

Effectiveness of RESET:a strategic executive treatment for executive dysfunctioning in patients with Parkinson's disease

In this multicentre randomised controlled trial (RCT), 43 patients with Parkinson’s disease (PD) were randomly allocated to either the experimental condition receiving cognitive rehabilitation including strategy training (ReSET; Strategic Executive Treatment, n = 24) or to the control condition receiving computerised repetitive practice training for attention (Cogniplus, n = 16). We expected that strategy training (ReSET) would be more effective than cognitive training (Cogniplus) in improving patients’ everyday life executive functioning. Neuropsychological assessment was administered at baseline, at 2 weeks and 3–5 months post-treatment. Primary outcome measure was the Role Resumption List (RRL). Secondary outcome measures were treatment goal attainment (TGA), Dysexecutive Questionnaire (DEX), Parkinson’s Disease Questionnaire (PDQ-39), Zarit Burden Interview (ZBI) and neuropsychological tests. No effects of treatment were found on the primary outcome measure and on neuropsychological tests, except for one test of attention. At 2 weeks and 3–5 months post-treatment, PD patients in both the ReSET and Cogniplus group reported a significant improvement in everyday life executive functioning, as measured with TGA and the DEX-self, with an advantage for ReSET only shortly after treatment. Given these results and that PD patients were able to adhere to these treatments despite their motor symptoms and fatigue (i.e., the drop-out rate was small), we conclude that both strategy training and cognitive training for impairments in EF might be beneficial and feasible for PD patients

Early factors for predicting discontinuation to subcutaneous Apomorphine infusion in Parkinson's disease:A prospective analysis of the Thai Apomorphine Registry

INTRODUCTION: Although continuous subcutaneous apomorphine infusion (CSAI) is an effective therapy for Parkinson's disease (PD) with motor fluctuations, data from Asian cohorts is limited. The therapy is often discontinued due to the complexity of its delivery. METHODS: Fifty-one PD patients undergoing CSAI as an add-on therapy were enrolled in the Thai Apomorphine Registry, an electronic database that recorded clinical characteristics and parameters during the 14-consecutive-day titration and long-term follow-up. Factors at the time of titration were documented in order to identify predictors of long-term discontinuation. RESULTS: Following initiation, PD patients were administered a mean CSAI dose of 5.89 mg/h (SD 1.36) over a mean time of 12.28 h (SD 1.90) each day. The mean follow-up period was 626.2 days (SD 619.17). Significant reductions in UPDRS-I, II, III, and IV scores, total NMSQ score, PDQ-8 score, daily off and dyskinesia hours, Timed Up and Go test, walking step test, levodopa-equivalent daily dose, number of times a day the levodopa was taken versus pre-CSAI values were observed (p < 0.05, each). Thirty-five (68.6%) patients discontinued during the follow-up period. Relative risks of variables recorded at the time of titration that determined discontinuation of CSAI therapy were an absence of full-time caregivers, achieving a daily off hours reduction <3.5 h, and NMSQ scores at the time of CSAI titration ≥9.5 points. CONCLUSION: Identifying factors that predict discontinuation of CSAI at the time of its initiation may help physicians to better understand the patient's drug response and how to manage them long-term