Diagnosis Of Idiopathic Parkinson's Disease Research Articles

Evaluation of Post-Swallow Residue with Visual Analysis of Swallowing Efficiency and Safety in Patients with Idiopathic Parkinson's Disease.

Objectives: Dysphagia is common in idiopathic Parkinson's disease (IPD) and is associated with impairments in both swallowing safety and swallowing efficiency. The goals of this study were to define post-swallow residue patterns in people with IPD and describe pathophysiological endoscopic findings affecting residue accumulation. Methods: This was a prospective single-blinded cross-sectional cohort study of patients with the diagnosis of IPD recruited from a Movement Disorder Clinic. Clinical variables included patient age, cognitive function, and measures of disease severity, and laryngoscopic examinations with a flexible endoscopic evaluation of swallowing (FEES) were completed for each patient. Visual Analysis of Swallowing Efficiency and Safety (VASES) was used to analyze FEES. Post-swallow residue outcomes and non-residue endoscopic outcomes including the Bowing index, Penetration Aspiration Scale (PAS) score, premature leakage, and build-up phenomenon were evaluated. Multiple regression models were used to evaluate factors affecting the residue at different anatomic levels. Results: Overall 53 patients completed the study. The multiple regression analyses showed a relation between (1) the presence of residue at the level of oropharynx and epiglottis with premature leakage, (2) the presence of residue at the level of the laryngeal vestibule and vocal folds with build-up phenomenon, and (3) the presence of residue at the level of the hypopharynx, laryngeal vestibule, and subglottis with airway invasion. Conclusion: Residue pattern during FEES is associated with specific swallow dysfunctions in IPD. Using residue localization and quantification may be a helpful tool in assessing the impact of targeted swallowing interventions in patients with IPD and dysphagia.

Clinical and Swallowing Characteristics Related With Respiratory Infection in Parkinsonism Patients.

To investigate the clinical and swallowing characteristics related to respiratory infection in patients with parkinsonism. One hundred and forty-two patients with parkinsonism who underwent videofluoroscopic swallowing studies (VFSS) were enrolled in this study. The initial clinical and VFSS characteristics were compared between patients with and without a history of respiratory infection in the past year. A multivariate logistic regression model was applied to identify clinical and swallowing characteristics related to respiratory infections. Patients with respiratory infections were older (74.75±10.20 years vs. 70.70±8.83 years, p=0.037), had a higher Hoehn and Yahr (H&Y) stage (stage IV-V, 67.9% vs. 49.1%; p=0.047), and were more likely to have a diagnosis of idiopathic Parkinson's disease (IPD) (67.9% vs. 41.2%, p=0.011) than those without respiratory infections. Among VFSS findings, bolus formation, premature bolus loss, oral transit time, pyriform sinus residues, pharyngeal wall coatings, and penetration/aspiration were significantly worse in patients with respiratory infections (p<0.05). Regarding clinical characteristics, higher H&Y stage (odds ratio [OR], 3.174; 95% confidence interval [CI], 1.226-8.216; p=0.017) and diagnosis of IPD (OR, 0.280, 95% CI, 0.111-0.706; p=0.007) were significantly related to respiratory infections in the multivariate analysis. Among VFSS findings, pyriform sinus residue (OR, 14.615; 95% CI, 2.257-94.623; p=0.005) and premature bolus loss (OR, 5.151; 95% CI, 1.047-25.338; p=0.044) were also significantly associated with respiratory infection. This study suggests that disease severity, diagnosis, pyriform sinus residue, and premature bolus loss observed in VFSS are associated with respiratory infection in patients with parkinsonism.

Relevance of 18F-DOPA visual and semi-quantitative PET metrics for the diagnostic of Parkinson disease in clinical practice: a machine learning-based inference study

PurposeTo decipher the relevance of visual and semi-quantitative 6-fluoro-(18F)-L-DOPA (18F-DOPA) interpretation methods for the diagnostic of idiopathic Parkinson disease (IPD) in hybrid positron emission tomography (PET) and magnetic resonance imaging.Material and methodsA total of 110 consecutive patients (48 IPD and 62 controls) with 11 months of median clinical follow-up (reference standard) were included. A composite visual assessment from five independent nuclear imaging readers, together with striatal standard uptake value (SUV) to occipital SUV ratio, striatal gradients and putamen asymmetry-based semi-quantitative PET metrics automatically extracted used to train machine learning models to classify IPD versus controls. Using a ratio of 70/30 for training and testing sets, respectively, five classification models—k-NN, LogRegression, support vector machine, random forest and gradient boosting—were trained by using 100 times repeated nested cross-validation procedures. From the best model on average, the contribution of PET parameters was deciphered using the Shapley additive explanations method (SHAP). Cross-validated receiver operating characteristic curves (cv-ROC) of the most contributive PET parameters were finally estimated and compared.ResultsThe best machine learning model (k-NN) provided final cv-ROC of 0.81. According to SHAP analyses, visual PET metric was the most important contributor to the model overall performance, followed by the minimum between left and right striatal to occipital SUV ratio. The 10-time cv-ROC curves of visual, min SUVr or both showed quite similar performance (mean area under the ROC of 0.81, 0.81 and 0.79, respectively, for visual, min SUVr or both).ConclusionVisual expert analysis remains the most relevant parameter to predict IPD diagnosis at 11 months of median clinical follow-up in 18F-FDOPA. The min SUV ratio appears interesting in the perspective of simple semi-automated diagnostic workflows.

Deep Learning Algorithm of 12-Lead Electrocardiogram for Parkinson Disease Screening.

Although idiopathic Parkinson's disease (IPD) is increasing with the aging population, there is no adequate screening test for early diagnosis of IPD. Cardiac autonomic dysfunction begins in the early stages of IPD, and an electrocardiogram (ECG) contains precise information on the heart. This study is to develop an ECG deep learning algorithm that can efficiently screen for IPD. Data were collected from 751 IPD patients (2,138 ECGs), 751 age and sex-matched non-IPD patients (2,673 ECGs) as a control group, and 297 drug-induced Parkinsonism (DPD) patients (875 ECGs) as a disease control group. ECG data were randomly divided into training set, validation set, and test set at a ratio of 6:2:2. We developed a deep-convolutional neural network (CNN) consisting of 16 layers with Bayesian optimization that classified IPD patients by ECG data. The robustness of the deep learning model was verified through 5-fold cross-validation. The AUROC of the model for detection of IPD was 0.924 (95% CI, 0.913-0.936) in the test set. That for detecting DPD was 0.473 (95% CI, 0.453-0.504). The sensitivities of the model according to Unified Parkinson's Disease Rating Scale III and Hoehn & Yahr scale were also similar. In conclusion, the CNN-based deep learning model using ECG data showed quite good performance in identifying IPD patients. Standardized 12-lead ECG test could be one of the clinically feasible candidate methods for early screening of IPD in the future.

Functional connectome automatically differentiates multiple system atrophy (parkinsonian type) from idiopathic Parkinson's disease at early stages.

Differentiating the parkinsonian variant of multiple system atrophy (MSA-P) from idiopathic Parkinson's disease (IPD) is challenging, especially in the early stages. This study aimed to investigate differences and similarities in the brain functional connectomes of IPD and MSA-P patients and use machine learning methods to explore the diagnostic utility of these features. Resting-state fMRI data were acquired from 88 healthy controls, 76 MSA-P patients, and 53 IPD patients using a 3.0T scanner. The whole-brain functional connectome was constructed by thresholding the Pearson correlation matrices of 116 regions, and topological properties were evaluated through graph theory approaches. Connectome measurements were used as features in machine learning models (random forest [RF]/logistic regression [LR]/support vector machine) to distinguish IPD and MSA-P patients. Regarding graph metrics, early IPD and MSA-P patients shared network topological properties. Both patient groups showed functional connectivity disruptions within the cerebellum-basal ganglia-cortical network, but these disconnections were mainly in the cortico-thalamo-cerebellar circuits in MSA-P patients and the basal ganglia-thalamo-cortical circuits in IPD patients. Among the connectome parameters, t tests combined with the RF method identified 15 features, from which the LR classifier achieved the best diagnostic performance on the validation set (accuracy=92.31%, sensitivity=90.91%, specificity=93.33%, area under the receiver operating characteristic curve=0.89). MSA-P and IPD patients show similar whole-brain network topological alterations. MSA-P primarily affects cerebellar nodes, and IPD primarily affects basal ganglia nodes; both conditions disrupt the cerebellum-basal ganglia-cortical network. Moreover, functional connectome parameters showed outstanding value in the differential diagnosis of early MSA-P and IPD.

Evaluation of Simvastatin as a Disease-Modifying Treatment for Patients With Parkinson Disease

Current treatments manage symptoms of Parkinson disease (PD), but no known treatment slows disease progression. Preclinical and epidemiological studies support the potential use of statins as disease-modifying therapy. To determine whether simvastatin has potential as a disease-modifying treatment for patients with moderate PD. This randomized clinical trial, a double-blind, parallel-group, placebo-controlled futility trial, was conducted between March 2016 and May 2020 within 23 National Health Service Trusts in England. Participants aged 40 to 90 years with a diagnosis of idiopathic PD, with a modified Hoehn and Yahr stage of 3.0 or less while taking medication, and taking dopaminergic medication with wearing-off phenomenon were included. Data were analyzed from May 2020 to September 2020, with additional analysis in February 2021. Participants were allocated 1:1 to simvastatin or matched placebo via a computer-generated random sequence, stratified by site and Hoehn and Yahr stage. In the simvastatin arm, participants entered a 1-month phase of simvastatin, 40 mg daily, followed by 23 months of simvastatin, 80 mg daily, before a 2-month washout period. The prespecified primary outcome was 24-month change in Movement Disorder Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) part III score measured while not taking medication (high scores indicate worse outcome). The primary futility analysis included participants who commenced the 80-mg phase and had valid primary outcome data. The safety analysis included all participants who commenced trial treatment and is reported by dose at time of event. Of 332 patients assessed for eligibility, 32 declined and 65 were ineligible. Of 235 recruited participants, 97 (41%) were female, 233 (99%) were White, and the mean (SD) age was 65.4 (9.4) years. A total of 216 patients progressed to the 80-mg dose. Primary outcome analysis (n = 178) indicated the simvastatin group had an additional deterioration in MDS-UPDRS III score while not taking medication at 24 months compared with the placebo group (1.52 points; 2-sided 80% CI, -0.77 to 3.80; 1-sided futility test P = .006). A total of 37 serious adverse events (AEs), including 3 deaths, and 171 AEs were reported for participants receiving 0-mg simvastatin; 37 serious AEs and 150 AEs were reported for participants taking 40 mg or 80 mg of simvastatin. Four participants withdrew from the trial because of an AE. In this randomized clinical trial, simvastatin was futile as a disease-modifying therapy in patients with PD of moderate severity, providing no evidence to support proceeding to a phase 3 trial. ISRCTN Identifier: 16108482.

Role of middle latency auditory evoked potentials in parkinsonism

Introduction: Middle latency auditory evoked potentials (MLAEPs) allow the assessment of the function of the central part of the auditory pathway. MLAEP abnormalities have been demonstrated in patients with Alzheimer’s and Parkinson’s disease with dementia. Objective: The objective of our study was to assess the MLAEP findings in patients with idiopathic Parkinson’s disease (IPD) and atypical parkinsonism (AP) and to determine whether MLAEPs could contribute to the differential diagnosis of IPD and AP. Methods: We included 75 participants (25 IPD patients, 25 AP, and 25 age-matched healthy control subjects). MLAEPs were recorded in all patients and control subjects as per the standard procedure for MLAEP recordings. Absent waveforms (Na and Pa waves) and prolonged latencies of individual waves were considered as abnormal MLAEP readings. Results: The Pb waveform was significantly absent in the patients with IPD and AP compared to control subjects (p = 0.02). The Pb waveform was significantly absent in the AP group compared to the IPD group (p = 0.03). The Pb waveform was significantly absent in the AP group without cognitive impairment compared to the IPD group without cognitive impairment (p = 0.003). There was no statistically significant difference between the patients with IPD with and without cognitive impairment (p = 0.07). There was no significant difference among the groups with respect to Na and Pa wave latencies. Other parameters such as Na–Pa amplitude and Nb–Pb amplitudes were not significant among the groups. Conclusion: The absence of Pb potential in AP is an electrophysiological clue for the diagnosis of AP in patients presenting with parkinsonism. MLAEPs can act as an electrophysiological adjunct to the clinical imaging markers in differentiating IPD from AP.

Risk of Parkinson Disease Among Adults With vs Without Posttraumatic Stress Disorder

Posttraumatic stress disorder (PTSD) in elderly men may be associated with increased risk of Parkinson disease (PD); thus, this group of patients needs to be monitored closely for timely, customized treatment. To evaluate the risk of PD in patients with PTSD compared with patients without PTSD. This population-based, retrospective, cohort study used data from Maccabi Health Care Services (MHS), the second largest health plan in Israel, spanning from 2000 to 2019. Participants included MHS members born before 1970 who received a diagnosis of PTSD in 2000 to 2015. Patients with PTSD who had PD before their first diagnosis were excluded. Data analysis was performed from February to June 2022. Incident PTSD was denoted by at least 1 diagnosis (1) given by psychiatrists, psychologists, or neurologists; (2) hospital discharge diagnosis; or (3) registered as a chronic diagnosis (defined as such by the primary care physician). The index date was defined as first diagnosis for the patients with PTSD and for the corresponding patients without PTSD. PD incident cases up to 2019 were ascertained by idiopathic PD diagnosis (1) given by a neurologist, (2) extracted from a hospital discharge report, or (3) registered as a chronic diagnosis. Patients with PD-like syndromes documentation after the last mention of PD were excluded. Of 8342 eligible patients, 8336 (99.9%) were matched to nonexposed patients in a 1:1 ratio by birth year and sex; 4303 patients (51.6%) were male, and the mean (SD) age at index was 55.8 (13.2) years. Patients with PTSD had a 1.48-fold (95% CI, 1.10-1.99) excess risk for PD, compared with patients without PTSD. An elevated risk of PD (hazard ratio, 1.95; 95% CI, 1.16-3.28) was recorded among men receiving a diagnosis of PTSD at age 72 years or older. These findings suggest that elderly men who receive a diagnosis of PTSD are at an increased risk of PD. Further studies are needed to corroborate these findings and to further assess the association of stress with PD risk.

Does Olfactory Dysfunction Correlate with Disease Progression in Parkinson's Disease? A Systematic Review of the Current Literature.

Background. Loss of olfaction is a well-established early feature of Parkinson’s disease (PD). Although olfactory dysfunction has been widely described as a prodromal feature of PD in the literature, whether it can be considered a biomarker of PD progression is still a matter of debate. Objective. The aim of this work is to define the possible relationship between the progression of olfactory dysfunction and other putative clinical hallmarks of PD over time, through a systematic review of the current literature. Methods. We conducted a systematic review of the literature on PubMed from inception to March 2022. We included only longitudinal studies conducted on patients with diagnosis of idiopathic PD who underwent olfactory function testing at baseline and repeated it at least once during follow-up. Results. Among 5740 records identified through database searching, nine longitudinal studies met full criteria and underwent data extraction. Conclusions. Olfaction seemed to decrease over time, albeit with a degree of fluctuation. Moreover, smell detection ability seems to deteriorate more rapidly in the early phase of disease, indicating a possible association with disease progression. More studies are needed to better understand the role of olfaction as a biomarker of PD progression over time.

Differential Diagnosis of Parkinsonism Based on Deep Metabolic Imaging Indices.

The clinical presentations of early idiopathic Parkinson disease (IPD) substantially overlap with those of atypical parkinsonian syndromes such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). This study aimed to develop metabolic imaging indices based on deep learning to support the differential diagnosis of these conditions. Methods: A benchmark Huashan parkinsonian PET imaging (HPPI, China) database including 1,275 parkinsonian patients and 863 nonparkinsonian subjects with 18F-FDG PET images was established to support artificial intelligence development. A 3-dimensional deep convolutional neural network was developed to extract deep metabolic imaging (DMI) indices and blindly evaluated in an independent cohort with longitudinal follow-up from the HPPI and an external German cohort of 90 parkinsonian patients with different imaging acquisition protocols. Results: The proposed DMI indices had less ambiguity space in the differential diagnosis. They achieved sensitivities of 98.1%, 88.5%, and 84.5%, and specificities of 90.0%, 99.2%, and 97.8%, respectively, for the diagnosis of IPD, MSA, and PSP in the blind-test cohort. In the German cohort, they resulted in sensitivities of 94.1%, 82.4%, and 82.1%, and specificities of 84.0%, 99.9%, and 94.1%, respectively. Using the PET scans independently achieved a performance comparable to the integration of demographic and clinical information into the DMI indices. Conclusion: The DMI indices developed on the HPPI database show the potential to provide an early and accurate differential diagnosis for parkinsonism and are robust when dealing with discrepancies between populations and imaging acquisitions.

The prevalence of impulsive compulsive behaviors in patients treated with apomorphine infusion: a retrospective analysis.

Impulsive compulsive behaviors (ICBs) can affect a significant number of Parkinson's disease (PD) patients. We have studied brain samples from a brain bank of PD patients who received apomorphine via continuous infusion in life to assess the prevalence and outcome of ICBs. A search on the Queen Square Brain Bank (QSBB) database for cases donated from 2005 to 2016 with a pathological diagnosis of idiopathic PD was conducted. Notes of all donors who used apomorphine via continuous infusion for at least three months were reviewed. Clinical and demographic data were collected, as well as detailed information on treatment, prevalence and outcomes of ICBs. 193 PD cases, 124 males and 69 females, with an average age at disease onset of 60.2 years and average disease duration of 17.2 years were reviewed. Dementia occurred in nearly half of the sample, depression in one quarter, and dyskinesias in a little over 40%. The prevalence of ICBs was 14.5%. Twenty-four individuals used apomorphine infusion for more than three months. Patients on apomorphine had younger age at disease onset, longer disease duration, and higher prevalence of dyskinesias. The prevalence of de novo ICB cases among patients on apomorphine was 8.3%. Apomorphine infusion was used for an average of 63.1 months on an average maximum dose of 79.5 mg per day. Ten patients remained on apomorphine until death. Apomorphine can be used as an alternative treatment for patients with previous ICBs as it has low risk of triggering recurrence of ICBs.

The starting distance of obstacle circumvention did not affect intersegmental coordination in individuals with Parkinson's disease.

Obstacle circumvention is a challenging task in Parkinson's disease (PD). Body segments adjustments, such as changing the direction of the trunk, followed by a change in the direction of the head, and modifications in the positioning of the feet, are necessary to circumvent an obstacle during walking. For that, individuals need to identify the distance to the obstacle, its characteristics (such as its dimension), and perform well-coordinated movements. However, PD is characterized by rigidity, which may be increased in the axial axis and compromise the task execution. Also, worsening sensory integration in PD may increase the time to perform these body segments adjustments, thus impairing the movement coordination when starting obstacle circumvention near to the obstacle. To determine if the starting distance (1.5m, 3m, or 5m) from the obstacle could modify the intersegmental coordination (specifically, the coordination between head, trunk, and pelvis) during the obstacle circumvention steps in individuals with PD. Fourteen individuals with a diagnosis of idiopathic PD and 15 neurologically healthy individuals (CG) from the community were included in this study. The participants were evaluated in three different gait conditions, according to the starting distance from the obstacle: 1.5m, 3m, and 5m away from the obstacle. Vector coding technique was employed to establish the coupling between head, trunk, and pelvis in the steps immediately before and during obstacle circumvention. Three-way ANOVA's (group, distance, and step) were calculated with the level of significance at p<0.05. For all couplings of coordination, there were no effects of distance. However, significant main effects of group and steps (p<0.05) were found for all couplings with different patterns of coordination: head/pelvis (group: in-phase and anti-phase variables; steps: anti-phase variable), head/trunk (group: trunk variable; steps: in-phase and anti-phase variables) and trunk/pelvis (group: anti-phase; steps: trunk and pelvis). Finally, only head/trunk coupling showed an interaction between group*steps. Individuals with PD showed 7.95% lower head movement (p<0.024) and 14.85% greater trunk movement than CG (p<0.002). Also, individuals with PD performed 17.56% greater head movement in the step before the circumvention compared to the step during circumvention (p<0.044). The starting distance from the obstacle did not influence the pattern of axial intersegmental coordination in both groups. However, how these segments interact in the preparation and during the obstacle circumvention are opposite in individuals with PD. While on the previous step to obstacle circumvention, the head movement was greater than the trunk, during the obstacle circumvention step, individuals with PD rotated the trunk more.

Investigation of the peripheral inflammation (neutrophil-lymphocyte ratio) in two neurodegenerative diseases of the central nervous system.

IntroductionAlzheimer’s disease (AD), and idiopathic Parkinson’s disease (IPD) are the neurodegenerative diseases of the central nervous system (CNS). Cognitive impairment is on the forefront in AD. However, IPD is a movement disorder. Inflammation was suggested to have an effect in the pathophysiology of these two diseases. Neutrophil–lymphocyte ratio (NLR) was shown to be a possible marker showing the peripheral inflammation. We aimed to investigate the NLR of patiens with the diagnosis of AD, and IPD, and individuals with no neurodegenerative disease.Materials and methodsA total of 100 patients with the diagnosis of IPD, and 94 with diagnosis of AD, and 61 healthy controls were included into the study. All the demographic, clinical, and laboratory data were retrospectively obtained from the hospital automated database system.ResultsThe NLR in the IPD group was found statistically significantly higher compared with the control group and the AD group (p < 0.001, p = 0.04, respectively). The age-adjusted values were statistically analyzed because of age difference. No statistically significant difference was detected between AD and control groups in terms of NLR (p = 0.6). The age-adjusted NLR value in the Parkinson’s group was found significantly higher compared to the control group (p = 0.02) and Alzheimer’s group (p = 0.03).DiscussionChronic inflammation has an important role in the emergence and progression of the chronic neurodegenerative diseases of the CNS. Our results show that the inflammation in the peripheral blood in IPD was more significant compared with the inflammation in AD.

Multidimensional Factors Can Explain the Clinical Worsening in People With Parkinson's Disease During the COVID-19 Pandemic: A Multicenter Cross-Sectional Trial.

Background: Self-reported clinical worsening by people with Parkinson's disease (PD) during social distancing may be aggravated in Brazil, where the e/tele-health system is precarious.Objectives: This study aims to investigate self-reported changes in motor and non-motor aspects during social distancing in people with PD living in Brazil and to investigate the factors that might explain these changes.Methods: In this multicenter cross-sectional trial, 478 people with a diagnosis of idiopathic PD (mean age = 67, SD = 9.5; 167 female) were recruited from 14 centers distributed throughout the five geographical regions of Brazil. The evaluators from each center applied a questionnaire by telephone, which included questions (previous and current period of social distancing) about the motor and non-motor experiences of daily living, quality of life, daily routine, and physical activity volume.Results: Self-reported clinical worsening in non-motor and motor aspects of daily life experiences (Movement Disorder Society-Unified PD Rating Scale—parts IB and II—emotional and mental health, and fear of falling) and in the quality of life was observed. Only 31% of the participants reported a guided home-based physical activity with distance supervision. Perceived changes in the quality of life, freezing of gait, decreased physical activity volume, daily routine, and fear of falling explained the self-reported clinical worsening (P < 0.05).Conclusions: Self-reported clinical worsening in people with PD living in Brazil during social distancing can also be aggravated by the precarious e/tele-health system, as perception of decreased physical activity volume and impoverishment in daily routine were some of the explanatory factors. Considering the multifaceted worsening, the implementation of a remote multi-professional support for these people is urgent.

Predicting Long-Term Outcome of Patients of Early Parkinsonism with Acute Levodopa Challenge Test.

The aim of this study was to evaluate the sensitivity and specificity of various outcomes of acute levodopa challenge test (ALCT) namely improvement of motor function, development of dyskinesia and intolerance; to predict the diagnosis of idiopathic Parkinson's disease (IPD) or Parkinson-plus syndrome; to predict levodopa responsiveness and levodopa-induced dyskinesia (LID) during long-term therapy. ALCT was performed on 89 patients with parkinsonism of <2 years and were followed up for 18 months. Improvement of UPDRSm by ≥30% was considered positive. The test was positive in 37 (43.5%) and negative in 48 (56.5%) of 85 patients completing it. Of the 75 patients completing 18 months' follow-up 34 (45.3%) were diagnosed as IPD. A positive ALCT predicted a clinical diagnosis of IPD with sensitivity and specificity of 97.4% and 70.7% respectively. The predictive value of ALCT for long-term levodopa responsiveness was less than predicting a diagnosis of IPD. While appearance of dyskinesia during ALCT had a low predictive value for future LID (sensitivity 14.3%), it had high predictive value for a diagnosis of multisystem atrophy (MSA) (91% specificity and 37.5% sensitivity). The appearance of symptoms of levodopa intolerance (SLI) during ALCT could predict a clinical diagnosis of MSA with high specificity (95.5%) and moderate sensitivity (50%). Levodopa responsiveness during ALCT was useful in predicting a diagnosis of IPD but not long-term response to levodopa. The development of dyskinesia during ALCT could not correctly predict LID, but could predict a diagnosis of MSA. The appearance of SLI during ALCT could also predict MSA correctly.

Prevalence and Clinical Features of Idiopathic Parkinson's Disease in Western Turkey.

We aimed to determine the prevalence and risk factors of idiopathic Parkinson's disease (IPD) in Western Turkey, which encompasses Edirne and its surrounding districts. In this study, 9887 individuals, able to communicate and agreed to participate in the study, were evaluated. The data was obtained by answering a face-to-face questionnaire consisting of 53 questions from volunteers living at 30 randomly selected family health centers in Edirne and its counties. The questionnaire included demographic information, questions to evaluate potential concomitant conditions, and questions regarding the symptomatology used in IPD diagnosis. Following the questionnaire, it was planned to determine the degree of IPD with the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hoehn and Yahr scale (HY) clinical rating scale in patients diagnosed with IPD to assess disease severity in patients diagnosed with IPD. Of the 9887 individuals, 118 were diagnosed with IPD according to the questionnaire results from Edirne and its districts, and the prevalence of IPD was 1.2%. Approximately, 58.4% of the patients with IPD were male and 41.6% were female, which was not significantly different (p=0.214). Non-motor symptoms such as difficulty urinating, anxiety, depression, fatigue, REM sleep behavior disorder, and difficulty falling asleep or staying asleep were also examined in patients diagnosed with IPD. Depression was identified in 45.7% of the cases, while the control group was 4.3% (p=0.001). Fatigue was identified in 46.8% of the cases and control group was 3.5% (p=0.002). IPD prevalence studies will increase the awareness in the community and provide early diagnosis and treatment as well as serve as a basis to increased life expectancy, reduce morbidity, and improve life quality.

Comparison of the Effects of COVID-19 Pandemic on Male and Female Gender in Patients Diagnosed with Idiopathic Parkinson's Disease: A Case of Sakarya Province, Turkey.

The study aims to evaluate the motor, non-motor, cognitive and psychiatric conditions of our patients diagnosed with Idiopathic Parkinson's Disease (IPD) before and after the COVID-19 pandemic and to investigate the effect of the pandemic on male and female genders. Ninety patients were included in the study. Demographic data such as age, gender, and duration of disease, type of disease of the patients were recorded. Patients were then divided into 2 groups: male and female. Movement disorders of both groups before the pandemic, disease stage determined by H&Y and UPDRS at the admission and after the pandemic, Levodopa equivalent dose used were recorded and all patients were surveyed to evaluate their motor, non-motor, cognitive, and psychiatric conditions during the COVID-19 pandemic. The effects of the COVID-19 pandemic on male and female genders were investigated. Of the patients, 40 were male and 50 were female. Daytime drowsiness, weakness, impaired walking, constipation, sleep disorders, and inability to turn in the bed worsened compared to the period before the pandemic. Yet, of the psychiatric symptoms, boredom, unhappiness, anhedonia, irritability, and tension were found to increase during the pandemic. There was a statistically significant difference in UPDRS, H&Y and disease stages before and after the COVID-19 pandemic in both groups, especially in the female group (p<0.05). Although it was more pronounced in female patients with IPD diagnosis, both motor and non-motor symptoms were found to worsen during the COVID-19 pandemic in both groups.

Differential Diagnosis of Parkinsonism with Deep Metabolic Imaging Biomarker – An Artificial Intelligence-Aided Multi-Cohort FDG PET Study

Background: The clinical presentation of early idiopathic Parkinson’s disease (IPD) substantially overlaps with that of atypical parkinsonian syndromes such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has proven useful in assisting in the differential diagnosis of these parkinsonian syndromes. The aim of this study was to develop a metabolic imaging biomarker based on deep learning to support the differential diagnosis of parkinsonism. Methods: In addition to 863 non-parkinsonian subjects, a total of 1275 parkinsonian patients were accessed who underwent FDG PET imaging, clinical evaluation, and follow-up, yielding clinically possible, definite, or confirmative diagnoses of IPD, MSA, and PSP. A 3D deep convolutional neural network was developed to extract a deep metabolic imaging (DMI) biomarker. The accuracy of the DMI biomarker was evaluated with a cross-validation and a blind test. The robustness of the DMI biomarker was assessed on patients with longitudinal follow-up. The functional basis of DMI biomarker was further investigated based on the saliency map of the obtained deep neural network. Findings: The proposed DMI biomarker achieved an area under the receiver operating characteristic curve of 0·986 for the differential diagnosis of IPD, 0·997 for MSA, and 0·982 for PSP in the cross-validation. In the blind test, the DMI biomarker resulted in sensitivities of 98·1%, 88·5%, and 84·5%, as well as specificities of 90·0%, 99·2%, and 97·8% for IPD, MSA, and PSP respectively. The integration of demographic information and clinical assessments to DMI biomarker resulted in slight improvements. Saliencies for the DMI biomarker were found in several parkinsonism-related regions such as midbrain, putamen, and cerebellum. Interpretation: The DMI biomarker based on deep learning shows potential to provide accurate differential diagnosis for parkinsonism on FDG PET. The functional regions behind the DMI biomarker are consistent with known parkinsonian pathology. Funding Statement: The work was supported by grants from the National Natural Science Foundation of China (No. 81771483, 81671239, 81361120393, 81401135, 81971641, 81902282, 91949118, 81771372), from the Ministry of Science and Technology of China (2016YFC1306504), Shanghai Municipal Science and Technology Major Project (No. 2017SHZDZX01, 2018SHZDZX03) and ZJ Lab, Shanghai Sailing Program (No. 18YF1403100). It was also supported by Swiss National Science Foundation (No. 188350) and Siemens Healthineers. Declaration of Interests: W.H.O is Hertie Senior Research Professor, supported by the Charitable Hertie Foundation, Frankfurt/Main, Germany. A.R. and K.S. received research support from Siemens Healthineer. Other authors report no financial interests or potential conflicts of interest regarding the subject matter of the manuscript. Ethics Approval Statement: All procedures performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All the data were from Parkinson's Disease Database and Samples Bank in Huashan Hospital. Ethics permission was obtained from the Institutional Review Board of Huashan Hospital and written consent was obtained from each subject after detailed explanation of the procedures.

Utility of Imaging of Nigrosome-1 on 3T MRI and Its Comparison with 18F-DOPA PET in the Diagnosis of Idiopathic Parkinson Disease and Atypical Parkinsonism.

Loss of nigrosome-1 on 3T and 7T magnetic resonance imaging (MRI) is a recently explored imaging biomarker in the diagnosis of neurodegenerative parkinsonism. This study was undertaken to evaluate the utility of imaging of nigrosome in the diagnosis of neurodegenerative parkinsonism on 3T MRI. An institution-based prospective case-control study was conducted at a tertiary care center in North India. 3T venous blood oxygen level-dependent (VenoBOLD) and high-resolution susceptibility-weighted imaging (SWI) imaging sequences in MRI were performed in 100 patients with parkinsonism (56 with idiopathic Parkinson's disease [IPD], 30 with young onset Parkinson's disease [YOPD], 12 with progressive supranuclear palsy, and 2 patients with multiple system atrophy) and 15 controls. Grading of nigrosome was done in both the sequences. Each patient underwent 18F-DOPA positron emission tomography (PET), detailed neurological examination including Hoen and Yahr (H&Y) staging and Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scoring. The diagnostic sensitivity and specificity of the detection of loss of nigrosome-1 on VenoBOLD and SWI sequence at 3T MR imaging were 90% and 66.7% and 94% and 80%, respectively. A weak negative correlation was found between the grading of the nigrosome and clinical parameters (H&Y and UPDRS III). There was no correlation between the side of nigrosome loss and clinical asymmetry. However, nigrosome imaging was not able to differentiate between Parkinson's disease and atypical parkinsonism. The loss of nigrosome-1 on 3T MRI on SWI and VenoBOLD sequences may serve as a potential imaging marker in the diagnosis of degenerative parkinsonian syndromes. However, it cannot differentiate between idiopathic Parkinson's disease and atypical parkinsonian syndromes.

Barthel Index and modified Rankin Scale: Psychometric properties during medication phases in idiopathic Parkinson disease.

Independence in activities of daily living (ADL) is one of the most important aspects in planning treatment for people with Parkinson disease (PD). The Barthel Index (BI) and modified Rankin Scale (mRS) are commonly used in neurological diseases. This study was conducted to confirm the validity and reliability of the BI and mRS in PD during ON and OFF medication phases. We included 260 individuals with a diagnosis of idiopathic PD. The disability in ADL was measured by the BI, mRS, Parkinson's Disease Questionnaire-39 (PDQ-39), Unified Parkinson Disease Rating Scale-Activities of Daily Living (UPDRS-ADL), and Schwab and England ADL scale (SE). Test-retest, inter-rater reliability, and internal consistency were assessed by the intra-class correlation (ICC) and Cronbach α coefficients. Dimensionality was evaluated by factor analysis. Convergent validity was assessed by the SE, Berg Balance Scale (BBS), PDQ-39 and UPDRS-ADL. For the 260 participants (187 [71.9%] males; mean [SD] age 60.3 [12.3] years), both the BI and mRS achieved an acceptable level of test-retest and inter-rater reliability (ICC=0.77 to 0.91) in ON and OFF medication phases. The Cronbach α for BI was 0.85 and 0.88, respectively. We found 1 and 2 factors for BI in ON and OFF phases, respectively. Investigation of convergent validity showed moderate to high correlation for the BI with the UPDRS-ADL, SE, PDQ-39 (ADL), BBS and mRS scores in ON and OFF phases (ρ=0.51-0.74) and mRS with SE, UPDRS-ADL, PDQ-39 (ADL) and BBS scores (ρ=0.48-0.82). The BI and mRS showed acceptable validity and reliability to measure the degree of disability in patients with PD in daily activities in both ON and OFF medication phases.