Istradefylline effects on tremor dominance (TD) and postural instability and gait difficulty (PIGD)
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ABSTRACT:
SUBMITTER: Torres-Yaghi Y
PROVIDER: S-EPMC10630111 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
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Project description:Characterizing motor subtypes of Parkinson's disease (PD) is an important aspect of clinical care that is useful for prognosis and medical management. Although all PD cases involve the loss of dopaminergic neurons in the brain, individual cases may present with different combinations of motor signs, which may indicate differences in underlying pathology and potential response to treatment. However, the conventional method for distinguishing PD motor subtypes involves resource-intensive physical examination by a movement disorders specialist. Moreover, the standardized rating scales for PD rely on subjective observation, which requires specialized training and unavoidable inter-rater variability. In this work, we propose a system that uses machine learning models to automatically and objectively identify some PD motor subtypes, specifically Tremor-Dominant (TD) and Postural Instability and Gait Difficulty (PIGD), from 3D kinematic data recorded during walking tasks for patients with PD (MDS-UPDRS-III Score, 34.7 ± 10.5, average disease duration 7.5 ± 4.5 years). This study demonstrates a machine learning model utilizing kinematic data that identifies PD motor subtypes with a 79.6% F1 score (N = 55 patients with parkinsonism). This significantly outperformed a comparison model using classification based on gait features (19.8% F1 score). Variants of our model trained to individual patients achieved a 95.4% F1 score. This analysis revealed that both temporal, spectral, and statistical features from lower body movements are helpful in distinguishing motor subtypes. Automatically assessing PD motor subtypes simply from walking may reduce the time and resources required from specialists, thereby improving patient care for PD treatments. Furthermore, this system can provide objective assessments to track the changes in PD motor subtypes over time to implement and modify appropriate treatment plans for individual patients as needed.
| S-EPMC10575216 | biostudies-literature
Project description:Background:Weight loss in Parkinson's disease (PD) patients is a common but poorly understood manifestation. Several studies have reported that weight changes could be related to motor symptoms, drug side effects, dysphagia, depression, and/or dementia. Weight loss in PD is not a benign phenomenon and it has several clinical and prognostic implications with increased morbidity and mortality. Thus, it is crucial to determine nutritional changes in PD patients in order to prevent malnutrition and improve their quality of life. Objective:To compare body composition and resting metabolic rates between PD patients and controls. Methods:A total of 64 PD patients and 52 controls were studied. The Hoehn-Yahr scale was used to determine the disease stage, clinical and epidemiological data were recorded from verbal questionnaire, Inbody S10® was used to collect corporal parameters, and FitMate system was used to assess the resting metabolic rate. Results:No significant differences were found between both experimental groups in age, gender, height, cholesterol levels, and the presence of hypertension, diabetes, and hypo/hyperthyroidism. However, the PD group showed lower body fat mass, whole-body fat percentage, and greater resting metabolic rate compared to controls (p < 0.05), with no significant differences in musculoskeletal mass. Parkinson's disease postural instability/gait difficulty (PD-PIGD) subtype showed lower body fat parameters, increased fat-free mass, and higher resting metabolic rates. Conclusions:These results suggest that PD patients present an increased resting metabolic rate associated with the postural instability/gait difficulty PD subtype, allowing a selective decrease of body fat mass and not musculoskeletal mass. Of note, several disease-related factors may contribute to this weight loss in PD patients, being a complex and multifactorial consequence. Our findings could likely be one of the many contributing factors. However, present findings may further add to our understanding of the phenomenon of weight loss in patients with PD.
| S-EPMC7103052 | biostudies-literature
Project description:The PIGD (postural instability / gait difficulty) subtype of Parkinson´s disease (PD) is associated with faster cognitive and motor decline. So far, there are no quantifiable biomarkers to aid clinical subtyping. Neurofilament light chain (NfL) is a highly specific marker of neuro-axonal damage and can be assessed in blood. Here, we investigated if serum NfL concentrations are associated with PIGD subtype and PIGD scores in PD patients at advanced disease stages. Furthermore, we evaluated if serum NfL is associated with motor and cognitive function assessed with MDS-UPDRS part III and Montreal cognitive assessment (MoCA). Serum NfL levels were analyzed with Single Molecule Assays (Simoa) in blood of 223 PD patients from the bioMARKers in Parkinson's Disease (MARK-PD) study. Serum NfL concentrations were higher in PIGD patients independent of age, sex and disease duration. In linear regression analysis, serum NfL levels were associated with MoCA, MDS-UPDRS III and PIGD scores in unadjusted models, but remained significant after adjustment only with PIGD scores. In conclusion, increased serum NfL levels were associated with PIGD subtype and PIGD scores in patients with advanced PD.
| S-EPMC8930951 | biostudies-literature
Project description:Parkinson disease (PD) is identified as tremor-dominant (TD) and postural instability and gait difficulty (PIGD) phenotypes. The relationships between motor phenotypes and cognitive impairment and the underlying mechanisms relating pathological proteins and neurotransmitters in cerebrospinal fluid (CSF) are unknown. We evaluated the motor symptoms and cognitive function by scales, and detected the levels of pathological proteins and neurotransmitters in CSF. TD group and PIGD group had significantly higher levels of total tau, tau phosphorylated at the position of threonine 181(P-tau181t), threonine 231, serine 396, serine 199 and lower β amyloid (Aβ)1-42 level in CSF than those in control group; PIGD group had significantly higher P-tau181t level and lower Aβ1-42 level than those in TD group. In PD group, PIGD severity was negatively correlated with MoCA score and Aβ1-42 level in CSF, and positively correlated with Hoehn-Yahr stage and P-tau181t level in CSF. In PIGD group, PIGD severity was negatively correlated with homovanillic acid (HVA) level in CSF, and HVA level was positively correlated with Aβ1-42 level in CSF. PIGD was significantly correlated with cognitive impairment, which underlying mechanism might be involved in Aβ1-42 aggregation in brain and relevant neurochemical disturbance featured by the depletion of HVA in CSF.
| S-EPMC5362957 | biostudies-literature
Project description:BackgroundVisual dysfunction, including abnormal stereopsis, is a significant non-motor symptom in Parkinson's disease (PD) that can reduce quality of life and appears early in the disease. Abnormal stereopsis is associated with worsening of bradykinesia and freezing of gait, though the exact pathways linking stereopsis to motor symptoms remain unclear. Furthermore, in PD patients, the pedunculopontine nucleus and laterodorsal tegmental complex play an active role in sensorimotor control, and these areas provide cholinergic projections. Cholinergic degeneration may be associated with symptoms such as abnormal stereopsis, postural instability, gait disturbances and cognitive impairment. Therefore, in this study, we hypothesized that a high postural instability and gait disturbance score would increase the risk of abnormal stereopsis in PD.MethodsWe designed a cross-sectional study and included 240 early PD patients without ophthalmologic problems other than abnormal stereopsis. To evaluate stereopsis, we used Titmus stereo test plates. Stereopsis testing was performed only once at the time of the patient's initial PD diagnosis. We collected data from medical history taking, scales, cognitive function tests, gait analysis, and tilt table tests. To analyze the potential risk factors for abnormal stereopsis in PD, we conducted a binary logistic stepwise selection analysis.ResultsAmong the total of 240 PD patients, 185 were in the normal stereopsis group and 55 were in the abnormal stereopsis group. In the analysis for risk factors related to abnormal stereopsis, the postural instability and gait difficulties (PIGD) subtype score was significantly associated with abnormal stereopsis. (95% confidence interval: 1.37-5.15).ConclusionsIn PD, particularly in PIGD subtype patients, abnormal stereopsis can lead to a decrease in the quality of sensory information, potentially interfering with feedback and adaptation processes. This, in turn, can negatively affect posture and gait, creating a vicious cycle.
| S-EPMC11756755 | biostudies-literature
Project description:ObjectiveTo test the hypothesis that postural instability with falling (PIF) and freezing of gait (FOG) are distinct subtypes of the postural instability/gait disturbance (PIGD) form of Parkinson's disease (PD).Methods499 PD subjects from the NeuroGenetics Research Consortium were studied using logistic regression to examine, in a cross sectional analysis, predictors of FOG and PIF. Potential predictors were from four spheres; demographic, clinical motor, clinical non-motor and genetic.ResultsFOG and PIF were both associated with greater gait subscores and lower tremor subscores on the Unified Parkinson's Disease Rating Scale (p ≤ 0.02). However, they differed with regard to demographic, non-motor and genetic predictors. FOG was associated with greater duration of disease, with ORs of 3.01 (95% CI 1.35 to 6.72) and 4.91 (95% CI 2.29 to 10.54) for third and fourth quartiles of duration, respectively, versus the lowest half of duration. The risk of having psychotic symptoms was also significantly increased (OR 3.02, 95% CI 1.41 to 6.49; p=0.004). FOG was inversely associated with the presence of the CYP2D6*4 allele (OR 0.41, 95% CI 0.21 to 0.80; p=0.009) suggesting a protective effect. PIF was associated with depression (OR 1.08, 95% CI 1.01 to 1.15; p<0.02) and was inversely associated with APOE ε4 (OR 0.21, 95% CI 0.05 to 0.87; p=0.03), again suggesting a protective effect.ConclusionFOG and PIF have different demographic, non-motor and genetic predictors suggesting that they may be pathophysiologically distinct subtypes of PIGD. These findings have implications in the discovery of therapeutic targets for these disabling features as well as for predicting outcomes of PD.
| S-EPMC4646086 | biostudies-literature
Project description:Leg dominance reflects the preferential use of one leg over another and is typically attributed to asymmetries in the neural circuitry. Detecting leg dominance effects on motor behavior, particularly during balancing exercises, has proven difficult. The current study applied a principal component analysis (PCA) on kinematic data, to assess bilateral asymmetry on the coordinative structure (hypothesis H1) or on the control characteristics of specific movement components (hypothesis H2). Marker-based motion tracking was performed on 26 healthy adults (aged 25.3 ± 4.1 years), who stood unipedally on a multiaxial unstable board, in a randomized order, on their dominant and non-dominant leg. Leg dominance was defined as the kicking leg. PCA was performed to determine patterns of correlated segment movements ("principal movements" PMks). The control of each PMk was characterized by assessing its acceleration (second-time derivative). Results were inconclusive regarding a leg-dominance effect on the coordinative structure of balancing movements (H1 inconclusive); however, different control (p = 0.005) was observed in PM3, representing a diagonal plane movement component (H2 was supported). These findings supported that leg dominance effects should be considered when assessing or training lower-limb neuromuscular control and suggest that specific attention should be given to diagonal plane movements.
| S-EPMC7139434 | biostudies-literature
Project description:BackgroundIn Parkinson's disease (PD), postural instability and gait disorder (PIGD) symptoms are associated with a worse prognosis for an unknown reason.ObjectiveThe objective was to explore the relationship between cannabinoid receptor type 1 (CB1R) availability and motor symptoms in PD with [18F]FMPEP-d2 positron emission tomography (PET).MethodsFifteen individuals with PD underwent [18F]FMPEP-d2 PET to measure cerebral CB1R availability. The Unified Parkinson's Disease Rating Scale motor part (UPDRS-III) was used to evaluate the motor symptoms.ResultsA negative correlation was observed between [18F]FMPEP-d2 VT and PIGD score (P = 0.002) as well as rigidity subscore (P < 0.001). Both clusters covered widespread areas of both hemispheres. In contrast, tremor or bradykinesia did not correlate to [18F]FMPEP-d2 VT.ConclusionsGait, postural instability, and rigidity in PD are associated with decreased CB1R availability, unlike tremor or bradykinesia, suggesting that the endocannabinoid system has a role in the pathophysiology of different motor symptoms in PD. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
| S-EPMC11752992 | biostudies-literature
Project description:The neuronal physiological correlates of clinical heterogeneity in human essential tremor are unknown. We now test the hypothesis that thalamic neuronal and EMG activities during intention essential tremor are similar to those of the intention tremor which is characteristic of cerebellar lesions. Thalamic neuronal firing was studied in a cerebellar relay nucleus (ventral intermediate, Vim) and in a pallidal relay nucleus (ventral oral posterior, Vop) during stereotactic surgery for the treatment of tremor. Nine patients with essential tremor were divided clinically into two categories: one with a substantial component of tremor with intention (termed intention ET) and the other without (postural ET). These types of essential tremor were compared with patients having intention tremor plus other clinical signs of cerebellar disease (cerebellar tremor). Neurons in patients with either intention ET or cerebellar tremor had lower firing rates and lower spike×EMG coherence than those in patients with postural ET. Patients with intention ET had a lower spike×EMG phase lead than those with postural ET. Overall, thalamic activity measures of intention ET were different from postural ET but not apparently different from those of cerebellar tremor. One patient with the intention ET (number 4) had a good response to a left thalamotomy and then suffered a right cerebellar hemispheric infarct five years later. After the stroke the intention ET recurred, which is consistent with our hypothesis that intention ET is similar to that of the intention tremor which is characteristic of cerebellar lesions.
| S-EPMC3889719 | biostudies-literature
Project description:BackgroundParkinson's Disease patients with predominant gait dysfunction appear to have reduced cortical thickness compared to other motor phenotypes. The extent to which advancing age or disease duration impact the pattern of these distinctions is unclear.ObjectiveWe examine if PD patients with predominant signs of postural instability and gait dysfunction are distinguished by distinct patterns of cerebral atrophy, and how these differences are influenced by age and disease duration.MethodsThe Unified Parkinson's Disease Rating Score (UPDRS) was administered to 196 PD patients (age = 61.4±8.9yrs) in the Off and On dopamine state. All completed a structural T1-weighted brain MRI. We defined 3 motor phenotypes: tremor dominant, akinetic-rigid, and postural instability with gait disorder. General linear modeling quantified cortical thickness in relation to disease duration, and motor improvement after dopaminergic therapy. Cortical thickness and subcortical volumes were compared between the three motor subtypes, after controlling for disease duration and age.ResultsWe identified 177/196 patients who met criteria for a motor subtype. When corrected for disease duration, postural-instability patients had marked cortical thinning of the bilateral frontal-temporal and posterior cortical regions (cuneus/precuneus). After regressing for age, reduced frontal thickness was evident in patients with gait dysfunction. Widespread cortical thinning was associated with increasing disease duration and reduced motor improvement to dopaminergic therapy.ConclusionsResults emphasize that the profile of motor signs, especially prominent gait manifestations, relate to cortical thinning in distinct regions. Unique patterns of atrophy appear to be driven by advancing pathology related to age and disease duration.
| S-EPMC5826542 | biostudies-literature