Laserlight visual cueing device for freezing of gait in Parkinson's disease: a case study of the biomechanics involved

AbstractBackground: Freezing of gait (FOG) is a serious gait disorder affecting up to two-thirds of people with Parkinson's disease (PD). Cueing has been explored as a method of generating motor execution using visual transverse lines on the floor. However, the impact of a laser light visual cue remains unclear. Objective: To determine the biomechanical effect of a laser cane on FOG in a participant with PD compared to a healthy age- and gender-matched control. Methods: The participant with PD and healthy control were given a task of initiating gait from standing. Electromyography (EMG) data were collected from the tibialis anterior (TA) and the medial gastrocnemius (GS) muscles using an 8-channel system. A 10-camera system (Qualisys) recorded movement in 6 degrees of freedom and a calibrated anatomical system technique was used to construct a full body model. Center of mass (COM) and center of pressure (COP) were the main outcome measures. Results: The uncued condition showed that separation of COM and COP took longer and was of smaller magnitude than the cued condition. EMG activity revealed prolonged activation of GS, with little to no TA activity. The cued condition showed earlier COM and COP separation. There was reduced fluctuation in GS, with abnormal, early bursts of TA activity. Step length improved in the cued condition compared to the uncued condition. Conclusion: Laserlight visual cueing improved step length beyond a non-cued condition for this patient indicating improved posture and muscle control

Learning Optimal Deep Projection of 18^{18}F-FDG PET Imaging for Early Differential Diagnosis of Parkinsonian Syndromes

Several diseases of parkinsonian syndromes present similar symptoms at early stage and no objective widely used diagnostic methods have been approved until now. Positron emission tomography (PET) with $^{18}$F-FDG was shown to be able to assess early neuronal dysfunction of synucleinopathies and tauopathies. Tensor factorization (TF) based approaches have been applied to identify characteristic metabolic patterns for differential diagnosis. However, these conventional dimension-reduction strategies assume linear or multi-linear relationships inside data, and are therefore insufficient to distinguish nonlinear metabolic differences between various parkinsonian syndromes. In this paper, we propose a Deep Projection Neural Network (DPNN) to identify characteristic metabolic pattern for early differential diagnosis of parkinsonian syndromes. We draw our inspiration from the existing TF methods. The network consists of a (i) compression part: which uses a deep network to learn optimal 2D projections of 3D scans, and a (ii) classification part: which maps the 2D projections to labels. The compression part can be pre-trained using surplus unlabelled datasets. Also, as the classification part operates on these 2D projections, it can be trained end-to-end effectively with limited labelled data, in contrast to 3D approaches. We show that DPNN is more effective in comparison to existing state-of-the-art and plausible baselines.Comment: 8 pages, 3 figures, conference, MICCAI DLMIA, 201

An Estimate of the Prevalence of Dementia in Idiopathic Parkinson's Disease

A review of the records for evidence of dementia using criteria adapted from the third edition of the Diagnostic and Statistical Manual of Mental Disorders in every patient (hospitalized and outpatient) with parkinsonism at a major medical center during an 18-month period revealed an overall prevalence of 10.9% in 339 patients with idiopathic Parkinson's disease. Demented patients were older, had a later age at onset of motor manifestations, and a more rapid progression of physical disability than nondemented patients. Duration of illness and levodopa use and the presence of tremor or depression were similar in demented and nondemented patients. Demented patients more often responded poorly or developed adverse effects to levodopa than nondemented patients. When Parkinson's disease began after age 70 years, dementia was noted over three times more frequently than when the disease began at an earlier age. The age-specific prevalence rate of dementia for patients older than 70 years was more than twice that for younger patients. Moreover, the number of records with evidence for dementia with idiopathic Parkinson's disease was 3.75 times greater than expected in comparison with data from a study of the prevalence of dementia in the elderly

Serum heart-type fatty acid-binding protein and cerebrospinal fluid tau: Marker candidates for dementia with Lewy bodies

Background: The measurement of biomarkers in cerebrospinal fluid (CSF) has gained increasing acceptance in establishing the diagnosis of some neurodegenerative diseases. Heart-type fatty acid-binding protein (H-FABP) was recently discovered in CSF and serum of patients with neurodegenerative diseases. Objective: We investigated H-FABP in CSF and serum alone and in combination with CSF tau protein to evaluate these as potential biomarkers for the differentiation between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Methods: We established H-FABP and tau protein values in a set of 144 persons with DLB (n = 33), Parkinson disease with dementia (PDD; n = 25), AD (n = 35) and nonclemented neurological controls (NNC; n = 51). Additionally, serum H-FABP levels were analyzed in idiopathic Parkinson disease patients without evidence of cognitive decline (n = 45) using commercially available enzyme-linked immunosorbent assays. We calculated absolute values of HFABP and tau protein in CSF and serum and established relative ratios between the two to obtain the best possible match for the clinical working diagnosis. Results: Serum HFABP levels were elevated in DLB and PDD patients compared with NNC and AD subjects. To better discriminate between DLB and AD, we calculated the ratio of serum H-FABP to CSF tau protein levels. At the arbitrary chosen cutoff ratio >= 8 this quotient reached a sensitivity of 91% and a specificity of 66%. Conclusion: Our results suggest that the measurement of CSF tau protein, together with H-FABP quantification in serum and CSF, and the ratio of serum H-FABP to CSF tau protein represent marker candidates for the differentiation between AD and DLB. Copyright (c) 2007 S. Karger AG, Basel

Functional or not functional; that's the question Can we predict the diagnosis functional movement disorder based on associated features?

Background and purpose Functional movement disorders (FMDs) pose a diagnostic challenge for clinicians. Over the years several associated features have been shown to be suggestive for FMDs. Which features mentioned in the literature are discriminative between FMDs and non-FMDs were examined in a large cohort. In addition, a preliminary prediction model distinguishing these disorders was developed based on differentiating features. Method Medical records of all consecutive patients who visited our hyperkinetic outpatient clinic from 2012 to 2019 were retrospectively reviewed and 12 associated features in FMDs versus non-FMDs were compared. An independentttest for age of onset and Pearson chi-squared analyses for all categorical variables were performed. Multivariate logistic regression analysis was performed to develop a preliminary predictive model for FMDs. Results A total of 874 patients were eligible for inclusion, of whom 320 had an FMD and 554 a non-FMD. Differentiating features between these groups were age of onset, sex, psychiatric history, family history, more than one motor phenotype, pain, fatigue, abrupt onset, waxing and waning over long term, and fluctuations during the day. Based on these a preliminary predictive model was computed with a discriminative value of 91%. Discussion Ten associated features are shown to be not only suggestive but also discriminative between hyperkinetic FMDs and non-FMDs. Clinicians can use these features to identify patients suspected for FMDs and can subsequently alert them to test for positive symptoms at examination. Although a first preliminary model has good predictive accuracy, further validation should be performed prospectively in a multi-center study

Anxiety and anxious-depression in Parkinson's disease over a 4-year period: A latent transition analysis

Background: Depression and anxiety in Parkinson's disease are common and frequently co-morbid, with significant impact on health outcome. Nevertheless, management is complex and often suboptimal. The existence of clinical subtypes would support stratified approaches in both research and treatment. Method: Five hundred and thirteen patients with Parkinson's disease were assessed annually for up to 4 years. Latent transition analysis (LTA) was used to identify classes that may conform to clinically meaningful subgroups, transitions between those classes over time, and baseline clinical and demographic features that predict common trajectories. Results: In total, 64.1% of the sample remained in the study at year 4. LTA identified four classes, a 'Psychologically healthy' class (approximately 50%), and three classes associated with psychological distress: one with moderate anxiety alone (approximately 20%), and two with moderate levels of depression plus moderate or severe anxiety. Class membership tended to be stable across years, with only about 15% of individuals transitioning between the healthy class and one of the distress classes. Stable distress was predicted by higher baseline depression and psychiatric history and younger age of onset of Parkinson's disease. Those with younger age of onset were also more likely to become distressed over the course of the study. Conclusions: Psychopathology was characterized by relatively stable anxiety or anxious-depression over the 4-year period. Anxiety, with or without depression, appears to be the prominent psychopathological phenotype in Parkinson's disease suggesting a pressing need to understanding its mechanisms and improve management

Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>

Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling

Ageing, masculinity and Parkinson's disease: Embodied perspectives

Parkinson&rsquo;s Disease (PD) presents as an illness which predominantly affects older men. However older men&rsquo;s lived experiences of PD, including how they are influenced by age and gender relations has seen little empirical study. Drawing on Watson&rsquo;s (2000) male body schema, this paper explores PD&rsquo;s effects on men&rsquo;s bodies, alongside how men engage with masculinities and ageing in order to make meaning from these experiences. Data is presented from 30 narrative and semi structured interviews with 15 men of various ages who were living with PD. Findings suggest that PD threatens a pragmatic embodiment expressed through men&rsquo;s everyday occupations; a visceral embodiment located in difficulties with the body&rsquo;s basic movements and intimate functions and an experiential embodiment concerned with emotions and sensations within and about the body. In addition, each dimension of men&rsquo;s embodiment also intersected with the ageing process, a process also shaped in turn by broader social and cultural concerns regarding the positions and possibilities of men&rsquo;s lives as they move through the life course. This paper concludes by discussing the implications of gender and ageing in understanding men&rsquo;s experiences of PD