Care of Late-Stage Parkinsonism: Resource Utilization of the Disease in Five European Countries.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease that leads to progressive disability. Cost studies have mainly explored the early stages of the disease, whereas late-stage patients are underrepresented. OBJECTIVE: The aim is to evaluate the resource utilization and costs of PD management in people with late-stage disease. METHODS: The Care of Late-Stage Parkinsonism (CLaSP) study collected economic data from patients with late-stage PD and their caregivers in five European countries (France, Germany, the Netherlands, UK, Sweden) in a range of different settings. Patients were eligible to be included if they were in Hoehn and Yahr stage >3 in the on state or Schwab and England stage at 50% or less. In total, 592 patients met the inclusion criteria and provided information on their resource utilization. Costs were calculated from a societal perspective for a 3-month period. A least absolute shrinkage and selection operator approach was utilized to identify the most influential independent variables for explaining and predicting costs. RESULTS: During the 3-month period, the costs were €20,573 (France), €19,959 (Germany), €18,319 (the Netherlands), €25,649 (Sweden), and €12,156 (UK). The main contributors across sites were formal care, hospitalization, and informal care. Gender, age, duration of the disease, Unified Parkinson's Disease Rating Scale 2, the EQ-5D-3L, and the Schwab and England Scale were identified as predictors of costs. CONCLUSION: Costs in this cohort of individuals with late-stage PD were substantially higher compared to previously published data on individuals living in earlier stages of the disease. Resource utilization in the individual sites differed in part considerably among these three parameters mentioned. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Kinect-based objective assessment of the acute levodopa challenge test in parkinsonism: a feasibility study.

INTRODUCTION: The acute levodopa challenge test (ALCT) is an important and valuable examination but there are still some shortcomings with it. We aimed to objectively assess ALCT based on a depth camera and filter out the best indicators. METHODS: Fifty-nine individuals with parkinsonism completed ALCT and the improvement rate (IR, which indicates the change in value before and after levodopa administration) of the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) was calculated. The kinematic features of the patients' movements in both the OFF and ON states were collected with an Azure Kinect depth camera. RESULTS: The IR of MDS-UPDRS III was significantly correlated with the IRs of many kinematic features for arising from a chair, pronation-supination movements of the hand, finger tapping, toe tapping, leg agility, and gait (rs = - 0.277 ~ - 0.672, P < 0.05). Moderate to high discriminative values were found in the selected features in identifying a clinically significant response to levodopa with sensitivity, specificity, and area under the curve (AUC) in the range of 50-100%, 47.22%-97.22%, and 0.673-0.915, respectively. The resulting classifier combining kinematic features of toe tapping showed an excellent performance with an AUC of 0.966 (95% CI = 0.922-1.000, P < 0.001). The optimal cut-off value was 21.24% with sensitivity and specificity of 94.44% and 87.18%, respectively. CONCLUSION: This study demonstrated the feasibility of measuring the effect of levodopa and objectively assessing ALCT based on kinematic data derived from an Azure Kinect-based system.

Neurological gait assessment.

Gait disorders are a common feature of neurological disease. The gait examination is an essential part of the neurological clinical assessment, providing valuable clues to a myriad of causes. Understanding how to examine gait is not only essential for neurological diagnosis but also for treatment and prognosis. Here, we review aspects of the clinical history and examination of neurological gait to help guide gait disorder assessment. We focus particularly on how to differentiate between common gait abnormalities and highlight the characteristic features of the more prevalent neurological gait patterns such as ataxia, waddling, steppage, spastic gait, Parkinson's disease and functional gait disorders. We also offer diagnostic clues for some unusual gait presentations, such as dystonic, stiff-person and choreiform gait, along with red flags that help differentiate atypical parkinsonism from Parkinson's disease.

Quantitative MRI protocol and decision model for a 'one stop shop' early-stage Parkinsonism diagnosis: Study design.

Differentiating among early-stage parkinsonisms is a challenge in clinical practice. Quantitative MRI can aid the diagnostic process, but studies with singular MRI techniques have had limited success thus far. Our objective is to develop a multi-modal MRI method for this purpose. In this review we describe existing methods and present a dedicated quantitative MRI protocol, a decision model and a study design to validate our approach ahead of a pilot study. We present example imaging data from patients and a healthy control, which resemble related literature.

Head-to-Head Comparison Between Rabbit Sign and EANM/SNMMI Criteria for the 18F-DOPA Visual Assessment of Parkinsonian Syndromes in PET/MRI: A Multiple Expert-Based and Blinded Controlled Study.

PURPOSE: The aim of this study was to compare the diagnostic performance of the rabbit visual pattern versus the one endorsed by the EANM/SNMMI for the diagnosis of parkinsonian syndromes in PET/MRI. PATIENTS AND METHODS: The 18F-DOPA PET images of 129 consecutive patients (65 Park+ and 64 controls) with 1 year of clinical follow-up were reviewed independently by 5 experienced readers on the same imaging workstation, blinded to the final clinical diagnosis. Two visual methods were assessed independently, with several days to months of interval: the criteria endorsed by EANM/SNMMI and the "rabbit" shape of the striate assessed on 3D MIP images. The sensitivities, specificities, likelihood ratios, and predictive values of the 2 diagnostic tests were estimated simultaneously by using the "comparison of 2 binary diagnostic tests to a paired design" method. RESULTS: The estimated 95% confidence interval (CI) of sensitivities and specificities ranged from 49.4% to 76.5% and from 83.2% to 97.7%, respectively. The 95% CI estimates of positive and negative likelihood ratios ranged from 3.8 to 26.7 and from 0.26 to 0.56, respectively. The 95% CI estimates of the positive and negative predictive values ranged from 78.1% to 96.7% and from 60.3% to 81.4%, respectively. For all the parameters, no statistical difference was observed between the 2 methods (P > 0.05). The rabbit sign reduced the readers' discrepancies by 25%, while maintaining the same performance. CONCLUSIONS: The rabbit visual pattern appears at least comparable to the current EANM/SNMMI reference procedure for the assessment of parkinsonian syndromes in daily clinical practice, without the need of any image postprocessing. Further multicenter prospective studies would be of relevance to validate these findings.

Bedside Assessment of Autonomic Dysfunction in Multiple System Atrophy.

Multiple system atrophy (MSA) is a rare, rapidly progressive neurodegenerative disorder of the adulthood, characterized by autonomic failure, parkinsonian and cerebellar features in various combinations. Distinguishing MSA from common clinical look-alikes such as Parkinson's disease, other atypical parkinsonian disorders or alternative causes of sporadic adult-onset cerebellar ataxia may be difficult, especially at early disease stages. Nonetheless, some simple and cost-effective screening tools help detecting important red flags guiding towards a MSA diagnosis. Here we outline which clinical pearls and bedside tests may disclose autonomic dysfunction in multiple domains, enabling an early MSA diagnosis and, even more importantly, personalized treatment.

Quantitative assessment of oculomotor function by videonystagmography in multiple system atrophy.

OBJECTIVE: To quantitatively assess oculomotor impairments in multiple system atrophy (MSA) and to explore their correlation with clinical characteristics. METHODS: We recruited 45 patients with MSA, including 21 with dominant ataxia (MSA-C), 24 with dominant parkinsonism (MSA-P), and 40 age-matched healthy controls. Detailed oculomotor performance in the horizontal direction was measured using videonystagmography (VNG). RESULTS: We found that the proportion of abnormal eye movements in patients with MSA was 93.3% (37.7%, 51.1%, 73.3%, 71.1%, and 37.8% on fixation and gaze-holding, without fixation, saccade, smooth pursuit, and optokinetic nystagmus tests, respectively). Patients with MSA-C showed significantly lower gains in smooth pursuit test and optokinetic nystagmus test, and a higher incidence of hypermetria in the saccade test than patients with MSA-P (all P < 0.05). No oculomotor deficits were correlated with age, age of onset, sex, disease duration, or Unified Multiple System Atrophy Rating Scale (USMARS) (all r < 0.25, P > 0.1). CONCLUSIONS: An extremely high incidence of oculomotor impairments could be observed using VNG in both the MSA-C and MSA-P subtypes, although there were some differences between them. SIGNIFICANCE: A comprehensive oculomotor examination could serve as a valuable tool in the diagnostic workup of patients with MSA.

Neurophysiological assessment of juvenile parkinsonism due to primary monoamine neurotransmitter disorders.

No studies have investigated voluntary movement abnormalities and their neurophysiological correlates in patients with parkinsonism due to inherited primary monoamine neurotransmitter (NT) disorders. Nine NT disorders patients and 16 healthy controls (HCs) were enrolled. Objective measurements of repetitive finger tapping were obtained using a motion analysis system. Primary motor cortex (M1) excitability was assessed by recording the input/output (I/O) curve of motor-evoked potentials (MEP) and using a conditioning test paradigm for short-interval intracortical inhibition (SICI) assessment. M1 plasticity-like mechanisms were indexed according to MEPs amplitude changes after the paired associative stimulation protocol. Patient values were considered abnormal if they were greater or lower than two standard deviations from the average HCs value. Patients with aromatic amino acid decarboxylase, tyrosine hydroxylase, and 6-pyruvoyl-tetrahydropterin synthase defects showed markedly reduced velocity (5/5 patients), reduced movement amplitude, and irregular rhythm (4/5 patients). Conversely, only 1 out of 3 patients with autosomal-dominant GTPCH deficiency showed abnormal movement parameters. Interestingly, none of the patients had a progressive reduction in movement amplitude or velocity during the tapping sequence (no sequence effect). Reduced SICI was the most prominent neurophysiological abnormality in patients (5/9 patients). Finally, the I/O curve slope correlated with movement velocity and rhythm in patients. We provided an objective assessment of finger tapping abnormalities in monoamine NT disorders. We also demonstrated M1 excitability changes possibly related to alterations in motor execution. Our results may contribute to a better understanding of the pathophysiology of juvenile parkinsonism due to dopamine deficiency.

Caregiver Burden in Late-Stage Parkinsonism and Its Associations.

BACKGROUND: Patients in the late stages of parkinsonism are highly dependent on others in their self-care and activities of daily living. However, few studies have assessed the physical, psychological and social consequences of caring for a person with late-stage parkinsonism. PATIENTS AND METHODS: Five hundred and six patients and their caregivers from the Care of Late Stage Parkinsonism (CLaSP) study were included. Patients' motor and non-motor symptoms were assessed using the UPDRS and Non-motor symptom scale (NMSS), Neuropsychiatric inventory (NPI-12), and caregivers' health status using the EQ-5D-3 L. Caregiver burden was assessed by the Zarit Burden Interview (ZBI). RESULTS: The majority of caregivers were the spouse or life partner (71.2%), and were living with the patient at home (67%). Approximately half of caregivers reported anxiety/depression and pain/discomfort (45% and 59% respectively). The factors most strongly associated with caregiver burden were patients' neuropsychiatric features on the total NPI score (r = 0.38, p < 0.0001), total NMSS score (r = 0.28, p < 0.0001), caring for male patients and patients living at home. Being the spouse, the hours per day assisting and supervising the patient as well as caregivers' EQ-5D mood and pain scores were also associated with higher ZBI scores (all p < 0.001). CONCLUSION: The care of patients with late stage parkinsonism is associated with significant caregiver burden, particularly when patients manifest many neuropsychiatric and non-motor features and when caring for a male patient at home.

The remote assessment of parkinsonism supporting the ongoing development of interventions in Gaucher disease.

Mutations in GBA which are causative of Gaucher disease in their biallelic form, are the most common genetic risk factor for Parkinson's disease (PD). The diagnosis of PD relies upon clinically defined motor features which appear after irreversible neurodegeneration. Prodromal symptoms of PD may provide a means to predict latent pathology, years before the onset of motor features. Previous work has reported prodromal features of PD in GBA mutation carriers, however this has been insufficiently sensitive to identify those that will develop PD. The Remote Assessment of Parkinsonism Supporting Ongoing Development of Interventions in Gaucher Disease (RAPSODI GD) study assesses a large cohort of GBA mutation carriers, to aid development of procedures for earlier diagnosis of PD.

Lay abstract Changes in a gene called GBA cause a rare condition called Gaucher disease and are the most common genetic risk factor for Parkinson's disease (PD). To diagnose PD, patients must show symptoms of disordered movement which only occur after irreversible brain cell loss. Earlier symptoms may allow for the prediction of PD, years before movement symptoms occur. Previous work has reported earlier symptoms of PD occurring in people with GBA changes, however these studies have not been able to identify those at risk of developing PD. The Remote Assessment of Parkinsonism Supporting Ongoing Development of Interventions in Gaucher Disease (RAPSODI GD) study assesses a large group of people with GBA changes, to help develop a way to diagnose PD earlier.

Differentiating neurodegenerative parkinsonian syndromes using vestibular evoked myogenic potentials and balance assessment.

OBJECTIVE: Vestibular evoked myogenic potentials (VEMP) were investigated to differentiate between parkinsonian syndromes. We correlated balance and VEMP parameters to investigate the VEMP brainstem circuits as possible origin for postural instability. METHODS: We assessed clinical status, ocular and cervical VEMP (oVEMP, cVEMP) and conducted a balance assessment (posturography, Activities-specific Balance Confidence Scale, Berg Balance Scale, modified Barthel Index) in 76 subjects: 30 with Parkinson's disease (PD), 16 with atypical parkinsonism (AP) and 30 healthy controls. VEMP were elicited by using a mini-shaker on the forehead. RESULTS: Patients with PD had a prolonged oVEMP n10 in comparison to controls and prolonged p15 compared to controls and AP. Patients with AP showed reduced oVEMP amplitudes compared to PD and controls. CVEMP did not differ between groups. Postural impairment was higher in AP compared to controls and PD, particularly in the rating scales. No correlations between VEMP and posturography were found. A support vector machine classifier was able to automatically classify controls and patient subgroups with moderate to good accuracy based on oVEMP latencies and balance questionnaires. CONCLUSIONS: Both oVEMP and posturography, but not cVEMP, may be differentially affected in PD and AP. We did not find evidence that impairment of the cVEMP or oVEMP pathways is directly related to postural impairment. SIGNIFICANCE: OVEMP and balance assessment could be implemented in the differential diagnostic work-up of parkinsonian syndromes.

Quantitative Assessment of Motor Response to a Low Subacute Levodopa Dose in the Differential Diagnosis of Parkinsonisms at Disease Onset: Data from the BoProPark Cohort.

BACKGROUND: Differential diagnosis between Parkinson's disease (PD) and atypical parkinsonisms (APs) may be difficult at disease onset. The response to levodopa (LD) is a key supportive feature but its definition is largely empirical. Studies evaluating this issue by quantitative tests are scanty. OBJECTIVE: We aimed to assess the utility of a subacute low LD dose kinetic-dynamic test in the differential diagnosis between PD and APs. It was applied at the baseline of a prospective follow-up in patients with parkinsonian signs within three years of disease motor onset ("BoProPark" cohort) and eventually diagnosed as PD or APs according to consensus criteria. METHODS: Patients under at least 3-month LD therapy received a first morning fasting dose of LD/benserazide or carbidopa (100/25 mg) and underwent simultaneous serial assessments of plasma LD concentration and alternate finger tapping frequency up to 3 h. The main outcome was the extent of LD motor response, calculated by the area under the 3 h tapping effect-time curve (AUC_ETap). A receiver operating characteristic (ROC) curve analysis was performed to establish the optimal AUC_ETap cut-off to differentiate PD and APs. RESULTS: The first 100 consecutive "BoProPark" patients were analyzed. Forty-seven patients were classified as possible, 37 as probable PD and 16 as APs. AUC_ETap medians were similar in the PD subgroups but reduced to a third in APs (p < 0.001). The optimal AUC_ETap cut-off value was >2186 [(tap/min) x min], with a sensitivity of 92% and a specificity of 75%. Accuracy of the test was 0.85 (95% CI 0.74-0.95), p < 0.0001. CONCLUSION: The estimation of 3 h AUC_ETap after a subacute low LD dose proved a reliable, objective tool to assess LD motor response in our cohort of patients. AUC_ETap value rounded to ≥2200 supports PD diagnosis, while lower values may alert to AP diagnoses.

Assessment of Parkinsonian gait in older adults with dementia via human pose tracking in video data.

BACKGROUND: Parkinsonism is common in people with dementia, and is associated with neurodegenerative and vascular changes in the brain, or with exposure to antipsychotic or other dopamine antagonist medications. The detection of parkinsonian changes to gait may provide an opportunity to intervene and address reversible causes. In this study, we investigate the use of a vision-based system as an unobtrusive means to assess severity of parkinsonism in gait. METHODS: Videos of walking bouts of natural gait were collected in a specialized dementia unit using a Microsoft Kinect sensor and onboard color camera, and were processed to extract sixteen 3D and eight 2D gait features. Univariate regression to gait quality, as rated on the Unified Parkinson's Disease Rating Scale (UPDRS) and Simpson-Angus Scale (SAS), was used to identify gait features significantly correlated to these clinical scores for inclusion in multivariate models. Multivariate ordinal logistic regression was subsequently performed and the relative contribution of each gait feature for regression to UPDRS-gait and SAS-gait scores was assessed. RESULTS: Four hundred one walking bouts from 14 older adults with dementia were included in the analysis. Multivariate ordinal logistic regression models incorporating selected 2D or 3D gait features attained similar accuracies: the UPDRS-gait regression models achieved accuracies of 61.4 and 62.1% for 2D and 3D features, respectively. Similarly, the SAS-gait models achieved accuracies of 47.4 and 48.5% with 2D or 3D gait features, respectively. CONCLUSIONS: Gait features extracted from both 2D and 3D videos are correlated to UPDRS-gait and SAS-gait scores of parkinsonism severity in gait. Vision-based systems have the potential to be used as tools for longitudinal monitoring of parkinsonism in residential settings.

Comprehensive assessment of PINK1 variants in Parkinson's disease.

Multiple genes have been associated with monogenic Parkinson's disease and Parkinsonism syndromes. Mutations in PINK1 (PARK6) have been shown to result in autosomal recessive early-onset Parkinson's disease. In the past decade, several studies have suggested that carrying a single heterozygous PINK1 mutation is associated with increased risk for Parkinson's disease. Here, we comprehensively assess the role of PINK1 variants in Parkinson's disease susceptibility using several large data sets totalling 376,558 individuals including 13,708 cases with Parkinson's disease and 362,850 control subjects. After combining these data, we did not find evidence to support a role for heterozygous PINK1 mutations as a robust risk factor for Parkinson's disease.

A method for fast automated assessment of the magnetic resonance parkinsonism index.

In patients with parkinsonian syndromes, and particularly during the early stages of the clinical disease, differentiating between idiopathic Parkinson's disease and progressive supranuclear palsy is challenging. Imaging plays an important role in early diagnosis, and the magnetic resonance parkinsonism index was shown to reliably differentiate between the two entities. Calculation of the index is a time-consuming process. We developed an algorithm allowing its automatic calculation based on 3D T1-weighted images, producing additional color-coded images for verification.

Palliative Care for Parkinson's Spectrum Disorders: an Emerging Approach.

Parkinson's spectrum disorders (PSD) are neurodegenerative parkinsonian conditions that carry a tremendous symptom burden. Palliative care is an interdisciplinary medical specialty that focuses on improving quality of life for patients and caregivers affected by serious life-limiting illnesses, at any stage of disease. Research and clinical programs into this emerging therapeutic approach remain limited. This review focuses on the role of palliative care in the treatment of patients with PSD. Gaps in knowledge and recommendations for future research are discussed.

Accuracy of Dopamine Transporter Imaging with 123I-Ioflupane in Hispanic and Non-Hispanic Patients.

Racial and ethnic disparities in the prevalence of neurodegenerative diseases exist. This study examined the agreement between gold standard diagnosis and visual assessment of dopamine transporter (DaT) imaging in Hispanic and non-Hispanic patients being evaluated for Parkinsonian syndromes (PS). Methods: A retrospective review of DaT imaging and demographic data was performed with institutional review board approval. Documented interpretation by visual assessment was used to classify scans as normal or abnormal. The gold standard for the final diagnosis of PS was determined by a neurologist after 2 or more years of clinical follow-up. Data were analyzed with a z-test for uncorrelated samples. Results: In 30 Hispanic patients, DaT imaging was abnormal in 17, normal in 12, and nondiagnostic in 1. Of those with abnormal imaging, PS was confirmed in 16 of 17. Of those with normal imaging, no PS was confirmed in any patient. Sensitivity was 100%, and specificity was 92%. The single patient with nondiagnostic imaging was excluded. Of 77 non-Hispanic patients, visual assessment of DaT imaging was abnormal in 51. Of those with abnormal imaging, PS was confirmed in 48 of 51. Of those with normal imaging, no PS was confirmed in 22 of 26. Sensitivity was 92%, and specificity was 88%. There was no statistically significant difference (z = 0.34) in the rates of agreement between the gold standard and DaT imaging in Hispanic versus non-Hispanic patients. The study sample size afforded a power of 0.60. Conclusion: No significant difference was found in the accuracy of DaT imaging between Hispanic and non-Hispanic patients. Accuracy was high for both groups.

Paw-Print Analysis of Contrast-Enhanced Recordings (PrAnCER): A Low-Cost, Open-Access Automated Gait Analysis System for Assessing Motor Deficits.

Gait analysis is used to quantify changes in motor function in many rodent models of disease. Despite the importance of assessing gait and motor function in many areas of research, the available commercial options have several limitations such as high cost and lack of accessible, open code. To address these issues, we developed PrAnCER, Paw-Print Analysis of Contrast-Enhanced Recordings, for automated quantification of gait. The contrast-enhanced recordings are produced by using a translucent floor that obscures objects not in contact with the surface, effectively isolating the rat's paw prints as it walks. Using these videos, our simple software program reliably measures a variety of spatiotemporal gait parameters. To demonstrate that PrAnCER can accurately detect changes in motor function, we employed a haloperidol model of Parkinson's disease (PD). We tested rats at two doses of haloperidol: high dose (0.30 mg/kg) and low dose (0.15 mg/kg). Haloperidol significantly increased stance duration and hind paw contact area in the low dose condition, as might be expected in a PD model. In the high dose condition, we found a similar increase in contact area but also an unexpected increase in stride length. With further research, we found that this increased stride length is consistent with the bracing-escape phenomenon commonly observed at higher doses of haloperidol. Thus, PrAnCER was able to detect both expected and unexpected changes in rodent gait patterns. Additionally, we confirmed that PrAnCER is consistent and accurate when compared with manual scoring of gait parameters.