Chronic intracranial recordings in the globus pallidus reveal circadian rhythms in Parkinson's disease.

Circadian rhythms have been shown in the subthalamic nucleus (STN) in Parkinson's disease (PD), but only a few studies have focused on the globus pallidus internus (GPi). This retrospective study investigates GPi circadian rhythms in a large cohort of subjects with PD (130 recordings from 93 subjects) with GPi activity chronically recorded in their home environment. We found a significant change in GPi activity between daytime and nighttime in most subjects (82.4%), with a reduction in GPi activity at nighttime in 56.2% of recordings and an increase in activity in 26.2%. GPi activity in higher frequency bands ( > 20 Hz) was more likely to decrease at night and in patients taking extended-release levodopa medication. Our results suggest that circadian fluctuations in the GPi vary across individuals and that increased power at night might be due to the reemergence of pathological neural activity. These findings should be considered to ensure successful implementation of adaptive neurostimulation paradigms in the real-world.

Speech, voice, and language outcomes following deep brain stimulation: A systematic review.

BACKGROUND: Deep brain stimulation (DBS) reliably ameliorates cardinal motor symptoms in Parkinson's disease (PD) and essential tremor (ET). However, the effects of DBS on speech, voice and language have been inconsistent and have not been examined comprehensively in a single study. OBJECTIVE: We conducted a systematic analysis of literature by reviewing studies that examined the effects of DBS on speech, voice and language in PD and ET. METHODS: A total of 675 publications were retrieved from PubMed, Embase, CINHAL, Web of Science, Cochrane Library and Scopus databases. Based on our selection criteria, 90 papers were included in our analysis. The selected publications were categorized into four subcategories: Fluency, Word production, Articulation and phonology and Voice quality. RESULTS: The results suggested a long-term decline in verbal fluency, with more studies reporting deficits in phonemic fluency than semantic fluency following DBS. Additionally, high frequency stimulation, left-sided and bilateral DBS were associated with worse verbal fluency outcomes. Naming improved in the short-term following DBS-ON compared to DBS-OFF, with no long-term differences between the two conditions. Bilateral and low-frequency DBS demonstrated a relative improvement for phonation and articulation. Nonetheless, long-term DBS exacerbated phonation and articulation deficits. The effect of DBS on voice was highly variable, with both improvements and deterioration in different measures of voice. CONCLUSION: This was the first study that aimed to combine the outcome of speech, voice, and language following DBS in a single systematic review. The findings revealed a heterogeneous pattern of results for speech, voice, and language across DBS studies, and provided directions for future studies.

Subthalamic nucleus-language network connectivity predicts dopaminergic modulation of speech function in Parkinson's disease.

Speech impediments are a prominent yet understudied symptom of Parkinson's disease (PD). While the subthalamic nucleus (STN) is an established clinical target for treating motor symptoms, these interventions can lead to further worsening of speech. The interplay between dopaminergic medication, STN circuitry, and their downstream effects on speech in PD is not yet fully understood. Here, we investigate the effect of dopaminergic medication on STN circuitry and probe its association with speech and cognitive functions in PD patients. We found that changes in intrinsic functional connectivity of the STN were associated with alterations in speech functions in PD. Interestingly, this relationship was characterized by altered functional connectivity of the dorsolateral and ventromedial subdivisions of the STN with the language network. Crucially, medication-induced changes in functional connectivity between the STN's dorsolateral subdivision and key regions in the language network, including the left inferior frontal cortex and the left superior temporal gyrus, correlated with alterations on a standardized neuropsychological test requiring oral responses. This relation was not observed in the written version of the same test. Furthermore, changes in functional connectivity between STN and language regions predicted the medication's downstream effects on speech-related cognitive performance. These findings reveal a previously unidentified brain mechanism through which dopaminergic medication influences speech function in PD. Our study sheds light into the subcortical-cortical circuit mechanisms underlying impaired speech control in PD. The insights gained here could inform treatment strategies aimed at mitigating speech deficits in PD and enhancing the quality of life for affected individuals.

Cervical percutaneous interferential current stimulation improves citric acid cough tests in patients with Parkinson's disease on medication.

Aspiration pneumonia is the leading cause of death in patients with Parkinson's disease. The incidence of silent aspiration is high in such patients owing to decreased pharyngeal and laryngeal sensation; thus, interventions for this condition may help prevent pneumonia. In this single-arm, open-label study, we used a cervical percutaneous interferential current stimulation device to activate pharyngeal and laryngeal sensory nerves. We evaluated its effectiveness in patients with Hoehn-Yahr stages 2-4 Parkinson's disease. The primary endpoint was the proportion of patients with a normal cough reflex after consuming 1% citric acid at the end of the intervention compared with baseline measurements. In total, 25 patients received neck percutaneous interferential current stimulation for 20 min twice weekly for 8 weeks. Afterward, the proportion of patients with a normal cough reflex after 1% citric acid consumption increased significantly (p = 0.001), whereas other indicators, such as tongue pressure, peak expiratory flow, and penetration or aspiration during videofluoroscopic examination, remained unchanged. A longer duration of illness, higher Unified Parkinson's Disease Rating Scale total scores, and higher levodopa equivalent daily doses were significantly associated with improved cough test outcomes. Hence, cervical percutaneous interferential current stimulation significantly improved cough reflexes and may improve silent aspiration. Trial Registration: Japan Registry of Clinical Trials, jRCTs062220013, first registered 09/05/2022.

A person-centered approach to characterizing longitudinal ambulatory impairment in Parkinson's disease.

Loss of ambulation is common and highly variable in Parkinson's disease (PD), and poorly understood from the perspectives of those with PD. Gaining insights to the anticipated perceived trajectories and their drivers, will facilitate patient-centered care. Latent class growth analysis, a person-centered mixture modelling approach, was applied to 16,863 people with PD stratified by early (N = 8612; < 3 years), mid (N = 6181; 3-10 years) and later (N = 2070; > 10 years) disease to discern clusters with similar longitudinal patterns of self-reported walking difficulty, measured by EuroQoL 5D-5L that is validated for use in PD. There were four clusters in early and mid-disease strata, with a fifth identified in later disease. Trajectories ranged from none to moderate walking difficulty, with small clusters with severe problems. The percentage of subjects with moderate (early = 17.5%, mid = 26.4%, later = 32.5%) and severe (early = 3.8%, mid = 7.4%, later = 15.4%) walking difficulty at baseline increased across disease duration groups. The trajectories tended to be stable with variability in moderate and severe groups. Across strata, clusters with moderate to severe problems were associated with more severe impairment, depression, anxiety, arthritis, higher BMI, lower income, and lower education, but no consistent race or gender differences. The findings reveal distinct longitudinal patterns in perceived difficulties in walking in PD.

The correlation of orthostatic hypotension in Parkinson disease with the disease course and severity and its impact on quality of life.

We investigated the correlation of orthostatic hypotension (OH) in Parkinson disease (PD) with the disease course and severity, and its possible impact on quality of life. 171 PD patients were recruited and divided into the PD-NOH (n = 91) and PD-OH groups (n = 80). Clinical data were collected. The severity and quality of life of PD patients were evaluated. The impact of disease severity was analyzed using logistic regression analysis. The ROC curve was plotted. There were significant differences (P < .05) between PD-NOH and PD-OH groups in terms of the disease course, non-motor symptoms (somnipathy), Hoehn&Yahr stage, LEDD score, RBDSQ score, PDQ-39 score, MMSE score, MoCA, MDS-UPDRS Part III scores during off- and on-periods, and NMSS score. Hoehn&Yahr stage (OR 4.950, 95% CI 1.516-16.157, P = .008) was closely associated with the risk of OH in PD. PDQ-39 score (OR 1.079, 95% CI 1.033-1.127, P = .001) in PD patients with OH further decreased. Patients with PD-OH experienced severe impairment in 4 dimensions of quality of life, including motor function, cognitive function, physical discomfort, and activities of daily living. Different clinical symptoms of PD-OH were positively correlated with PDQ39 subscales. The area under the ROC curve of the Hoehn&Yahr stage in predicting the occurrence of OH was 0.679 (95% CI 0.600-0.758), and that of the Hoehn&Yahr stage combined with levodopa equivalent dose, and MDS-UPDRS Part III score during off-period was 0.793 (95% CI 0.727-0.862). Higher Hoehn&Yahr stage is associated with increased risk of OH in PD patients, and deteriorated quality of life of PD patients. Patients with different OH symptoms are affected in different dimensions of their quality of life. The Hoehn & Yahr stage can independently predict the risk of OH in PD patients.

Probabilistic stimulation mapping from intra-operative thalamic deep brain stimulation data in essential tremor.

Deep brain stimulation (DBS) is a therapy for Parkinson's disease (PD) and essential tremor (ET). The mechanism of action of DBS is still incompletely understood. Retrospective group analysis of intra-operative data recorded from ET patients implanted in the ventral intermediate nucleus of the thalamus (Vim) is rare. Intra-operative stimulation tests generate rich data and their use in group analysis has not yet been explored.Objective.To implement, evaluate, and apply a group analysis workflow to generate probabilistic stimulation maps (PSMs) using intra-operative stimulation data from ET patients implanted in Vim.Approach.A group-specific anatomical template was constructed based on the magnetic resonance imaging scans of 6 ET patients and 13 PD patients. Intra-operative test data (total:n= 1821) from the 6 ET patients was analyzed: patient-specific electric field simulations together with tremor assessments obtained by a wrist-based acceleration sensor were transferred to this template. Occurrence and weighted mean maps were generated. Voxels associated with symptomatic response were identified through a linear mixed model approach to form a PSM. Improvements predicted by the PSM were compared to those clinically assessed. Finally, the PSM clusters were compared to those obtained in a multicenter study using data from chronic stimulation effects in ET.Main results.Regions responsible for improvement identified on the PSM were in the posterior sub-thalamic area (PSA) and at the border between the Vim and ventro-oral nucleus of the thalamus (VO). The comparison with literature revealed a center-to-center distance of less than 5 mm and an overlap score (Dice) of 0.4 between the significant clusters. Our workflow and intra-operative test data from 6 ET-Vim patients identified effective stimulation areas in PSA and around Vim and VO, affirming existing medical literature.Significance.This study supports the potential of probabilistic analysis of intra-operative stimulation test data to reveal DBS's action mechanisms and to assist surgical planning.

Impaired sequence manipulation in non-demented patients with progressive supranuclear palsy.

PURPOSE: Sequential working memory is the ability to maintain and manipulate sequential information at a second time scale. Patients with progressive supranuclear palsy (PSP) or Parkinson's disease (PD) perform poorly in tests that require the flexible arrangement of thoughts or actions. This study investigated whether sequential working memory is differently impaired in patients with PSP versus PD. METHOD: Twenty-nine patients with PSP Richardson's syndrome (PSP-RS), 36 patients with PD, and 36 healthy controls (HC) completed 3 well-established neuropsychological tests, including digit span forward (DST-F), digit span backward (DST-B), and adaptive digit ordering tests (DOT-A). The DST-F required maintaining digit sequences, and the DST-B and DOT-A required maintaining and manipulating digit sequences. FINDING: The PSP-RS group scored lower than the PD and HC groups in the DST-B and DOT-A but not in the DST-F, indicating that the ability to manipulate sequences was impaired, but the maintenance ability was preserved in PSP-RS patients. Moreover, in PSP-RS, the DST-B score negatively correlated with the severity of motor symptoms. The actual levodopa dose positively correlated with the DST-B ordering cost (DST-F score vs. DST-B score). The PSP patients who took a greater dose of levodopa tended to have higher DST-B ordering cost. There was no effect of levodopa on DST-B or DOT-A in PD. CONCLUSION: These results suggested that the ability to manipulate sequence was already reduced in patients with PSP-RS and was worse than in patients with PD.

Clinical value of video oculomotor evaluation in the differential diagnosis of multiple system atrophy and Parkinson's disease.

BACKGROUND: Multiple system atrophy (MSA) is a neurodegenerative disease that progresses rapidly and has a poor prognosis. This study aimed to assess the value of video oculomotor evaluation (VOE) in the differential diagnosis of MSA and Parkinson's disease (PD). METHODS: In total, 28 patients with MSA, 31 patients with PD, and 30 age- and sex-matched healthy controls (HC) were screened and included in this study. The evaluation consisted of a gaze-holding test, smooth pursuit eye movement (SPEM), random saccade, and optokinetic nystagmus (OKN). RESULTS: The MSA and PD groups had more abnormalities and decreased SPEM gain than the HC group (64.29%, 35.48%, 10%, p < .001). The SPEM gain in the MSA group was significantly lower than that in the PD group at specific frequencies. Patients with MSA and PD showed prolonged latencies in all saccade directions compared with those with HC. However, the two diseases had no significant differences in the saccade parameters. The OKN gain gradually decreased from the HC to the PD and the MSA groups (p < .05). Compared with the PD group, the gain in the MSA group was further decreased in the OKN test at 30°/s (Left, p = .010; Right p = .016). Receiver operating characteristic curves showed that the combination of oculomotor parameters with age and course of disease could aid in the differential diagnosis of patients with MSA and PD, with a sensitivity of 89.29% and a specificity of 70.97%. CONCLUSIONS: The combination of oculomotor parameters and clinical data may aid in the differential diagnosis of MSA and PD. Furthermore, VOE is vital in the identification of neurodegenerative diseases.

Osteoporosis in Parkinson's disease and the role of lean body mass: a cross-sectional study in a Brazilian tertiary center.

Background: Parkinson's disease (PD) is the second most common neurodegenerative illness and has the highest increase rate in recent years. There is growing evidence to suggest that PD is linked to higher osteoporosis rates and risk of fractures. Objective: This study aims to estimate the prevalence and factors associated with osteoporosis as defined by the National Osteoporosis Foundation (NOF) and World Health Organization in patients with mild to moderate PD. Methods: We performed a cross-sectional study at a tertiary public hospital in Fortaleza, Brazil, dating from May 2021 until April 2022. The study sample was comprised of patients with mild to moderate PD who were at least 40 years old and who had the ability to walk and stand unassisted. Bone Mineral Density (BMD) of both the hip (neck of the femur) and the lumbar spine were obtained via properly calibrated Dual Energy X-ray Absorptiometry (DXA) scanning. The FRAX (Fracture Risk Assessment Tool) score was used to determine a person's 10-year risk of major osteoporotic fracture. The Revised European Working Group on Sarcopenia in Older People (EWGSOP 2) was used as a basis to confirm a sarcopenia diagnosis with the following parameters: low muscle strength gauged by handgrip strength and low muscle quantity by DXA. Physical performance was carefully evaluated by using the Short Physical Performance Battery test. Osteoporosis and osteopenia were diagnosed following the NOF guidelines and WHO recommendations. Results: We evaluated 107 patients in total, of whom 45 (42%) were women. The group's mean age was 68 ± 9 years, and the mean disease time span was 9.9 ± 6.0 years and mean motor UPDRS was 43 ± 15. We found that 42.1% and 34.6% of the sample had osteopenia and osteoporosis following NOF criteria, respectively, and 43% and 33.6% following the WHO recommendations. Lower lean appendicular mass was associated to osteopenia and osteoporosis in multinomial logistic regression analysis in both diagnostic criteria. Conclusion: Our findings provide additional evidence for the protective role of lean mass against osteoporosis in patients with PD.

Subthalamic nucleus synchronization between beta band local field potential and single-unit activity in Parkinson's disease.

Local field potential (LFP) oscillations in the beta band (13-30 Hz) in the subthalamic nucleus (STN) of Parkinson's disease patients have been implicated in disease severity and treatment response. The relationship between single-neuron activity in the STN and regional beta power changes remains unclear. We used spike-triggered average (STA) to assess beta synchronization in STN. Beta power and STA magnitude at the beta frequency range were compared in three conditions: STN versus other subcortical structures, dorsal versus ventral STN, and high versus low beta power STN recordings. Magnitude of STA-LFP was greater within the STN compared to extra-STN structures along the trajectory path, despite no difference in percentage of the total power. Within the STN, there was a higher percent beta power in dorsal compared to ventral STN but no difference in STA-LFP magnitude. Further refining the comparison to high versus low beta peak power recordings inside the STN to evaluate if single-unit activity synchronized more strongly with beta band activity in areas of high beta power resulted in a significantly higher STA magnitude for areas of high beta power. Overall, these results suggest that STN single units strongly synchronize to beta activity, particularly units in areas of high beta power.

Detecting the symptoms of Parkinson's disease with non-standard video.

BACKGROUND: Neurodegenerative diseases, such as Parkinson's disease (PD), necessitate frequent clinical visits and monitoring to identify changes in motor symptoms and provide appropriate care. By applying machine learning techniques to video data, automated video analysis has emerged as a promising approach to track and analyze motor symptoms, which could facilitate more timely intervention. However, existing solutions often rely on specialized equipment and recording procedures, which limits their usability in unstructured settings like the home. In this study, we developed a method to detect PD symptoms from unstructured videos of clinical assessments, without the need for specialized equipment or recording procedures. METHODS: Twenty-eight individuals with Parkinson's disease completed a video-recorded motor examination that included the finger-to-nose and hand pronation-supination tasks. Clinical staff provided ground truth scores for the level of Parkinsonian symptoms present. For each video, we used a pre-existing model called PIXIE to measure the location of several joints on the person's body and quantify how they were moving. Features derived from the joint angles and trajectories, designed to be robust to recording angle, were then used to train two types of machine-learning classifiers (random forests and support vector machines) to detect the presence of PD symptoms. RESULTS: The support vector machine trained on the finger-to-nose task had an F1 score of 0.93 while the random forest trained on the same task yielded an F1 score of 0.85. The support vector machine and random forest trained on the hand pronation-supination task had F1 scores of 0.20 and 0.33, respectively. CONCLUSION: These results demonstrate the feasibility of developing video analysis tools to track motor symptoms across variable perspectives. These tools do not work equally well for all tasks, however. This technology has the potential to overcome barriers to access for many individuals with degenerative neurological diseases like PD, providing them with a more convenient and timely method to monitor symptom progression, without requiring a structured video recording procedure. Ultimately, more frequent and objective home assessments of motor function could enable more precise telehealth optimization of interventions to improve clinical outcomes inside and outside of the clinic.

The influence of accelerated brain aging on coactivation pattern dynamics in Parkinson's disease.

Aging is widely acknowledged as the primary risk factor for brain degeneration, with Parkinson's disease (PD) tending to follow accelerated aging trajectories. We aim to investigate the impact of structural brain aging on the temporal dynamics of a large-scale functional network in PD. We enrolled 62 PD patients and 32 healthy controls (HCs). The level of brain aging was determined by calculating global and local brain age gap estimates (G-brainAGE and L-brainAGE) from structural images. The neural network activity of the whole brain was captured by identifying coactivation patterns (CAPs) from resting-state functional images. Intergroup differences were assessed using the general linear model. Subsequently, a spatial correlation analysis between the L-brainAGE difference map and CAPs was conducted to uncover the anatomical underpinnings of functional alterations. Compared to HCs (-3.73 years), G-brainAGE was significantly higher in PD patients (+1.93 years), who also exhibited widespread elevation in L-brainAGE. G-brainAGE was correlated with disease severity and duration. PD patients spent less time in CAPs involving activated default mode and the fronto-parietal network (DMN-FPN), as well as the sensorimotor and salience network (SMN-SN), and had a reduced transition frequency from other CAPs to the DMN-FPN and SMN-SN CAPs. Furthermore, the pattern of localized brain age acceleration showed spatial similarities with the SMN-SN CAP. Accelerated structural brain aging in PD adversely affects brain function, manifesting as dysregulated brain network dynamics. These findings provide insights into the neuropathological mechanisms underlying neurodegenerative diseases and imply the possibility of interventions for modifying PD progression by slowing the brain aging process.

The decline in postural balance has a negative impact on the performance of functional tasks in individuals with Parkinson's Disease.

INTRODUCTION: An accurate assessment of balance problems is critical for decreasing the risk of falling in patients with Parkinson's Disease (PD). Reliable diagnostic tools such as Computerized Dynamic Posturography (CDP) are not feasible for the clinical setting. Therefore, the present study's aim was to assess the correlation between the clinical Balance Evaluation Systems Test (BESTest) and CDP. METHODS: 20 male older adults with Parkinson's Disease (PD) were included in this study. Participants first executed the Sit-To-Stand (STS), Step/Quick turn (SQT), and Step Up and Over (SUO) tests on a Balance Master® force platform, followed by a clinical balance evaluation using the BESTest. RESULTS: Four outcomes of the CDP were negatively correlated with one or more BESTest domains or total BESTest score: STS sway velocity was negatively correlated with the anticipatory postural adjustment (p = 0.02) and sensory orientation (p = 0.01) domains. SQT turn time was negatively correlated with biomechanical restriction (for turns to the left, p = 0.01, and right, p = 0.03, respectively), postural response (p = 0.01, p = 0.01), dynamic balance during gait (p = 0.007, p = 0.001), and total score (p = 0.02, p = 0.01). Step over time to the right in SUP was negatively correlated with the limits of the stability domain (p = 0.002) and total BESTest score (p = 0.020). SUO impact index was negatively correlated with the anticipatory postural adjustment domain (p = 0.01). CONCLUSION: This study shows that several BESTest domains are significantly correlated with CDP outcomes, demonstrating that the BESTest can be used as a more clinically feasible alternative for computerized posturography, without loss of information.

Relationship of Hearing Loss to Parkinson's Disease, Dementia, and APOE Genotype in Adults.

Background: Hearing loss has been recognized as a risk factor for dementia and non-motor features of Parkinson's disease (PD). The apolipoprotein E (APOE) protein contributes to maintenance and repair of neuronal cell membranes, causing age-related disorders. This study aimed to analyze the impact of hearing loss on cognitive impairment, PD severity, and APOE gene expression in these patients. Methods: A total of 72 out-patients diagnosed with either PD or hearing loss were enrolled in this study. The hearing assessment included pure-tone audiometry, speech reception thresholds, and speech discrimination ability. Dementia was assessed by filling out the Clinical Dementia Rating and Mini-Mental State Examination questionnaires. The severity of PD was assessed using the Modified Hoehn and Yahr scale. Blood samples were tested for the gene expression of APOE. Results: Out of the 72 cases, there were 44 males and 28 females, with an average age of 64.4 ± 9.1 years. A total of 41 out of 72 cases had dementia and had a worse hearing threshold than those without dementia (47.1 ± 24.4 vs. 31.7 ± 22.1 dB, p = 0.006). A total of 58 patients were diagnosed with PD, with 14 of them classified as having severe symptoms (Modified Hoehn and Yahr scale > 2). Patients with severe PD were found to have a worse hearing threshold (49.6 ± 28.3 vs. 30.3 ± 17.8 dB, p = 0.028) and higher prevalence of dementia (12/14 vs. 18/44, p = 0.006). Among 10 individuals with the APOE ε4 gene, the prevalence of dementia was higher than those without the ε4 allele (9/10 vs. 32/62, p = 0.036). Conclusions: Hearing loss is common in severe PD and in dementia patients. Severe PD has a negative impact on the hearing threshold and cognitive dysfunction. Patients with APOE ε4 have a higher prevalence of dementia.

The effects of L-DOPA on gait abnormalities in a unilateral 6-OHDA rat model of Parkinson's disease.

Parkinson's Disease (PD) is a neurodegenerative movement disorder characterized by dopamine (DA) cell loss in the substantia nigra pars compacta (SNc). As PD progresses, patients display disruptions in gait such as changes in posture, bradykinesia, and shortened stride. DA replacement via L-DOPA alleviates many PD symptoms, though its effects on gait are not well demonstrated. This study aimed to assess the relationship between DA lesion, gait, and deficit-induced reversal with L-DOPA. To do so, Sprague-Dawley rats (N = 25, 14 males, 11 females) received unilateral medial forebrain bundle (MFB) DA lesions with 6-hydroxydopamine (6-OHDA). An automated gait analysis system assessed spatiotemporal gait parameters pre- and post-lesion, and after various doses of L-DOPA (0, 3, or 6 mg/kg; s.c.). The forepaw adjusting steps (FAS) test was implemented to evaluate lesion efficacy while the abnormal involuntary movements (AIMs) scale monitored the emergence of L-DOPA-induced dyskinesia (LID). High performance liquid chromatography (HPLC) assessed changes in brain monoamines on account of lesion and treatment. Results revealed lesion-induced impairments in gait, inclusive of max-contact area and step-sequence alterations that were not reversible with L-DOPA. However, the emergence of AIMs were observed at higher doses. Post-mortem, 6-OHDA lesions induced a loss of striatal DA and norepinephrine (NE), while prefrontal cortex (PFC) displayed noticeable reduction in NE but not DA. Our findings indicate that hemiparkinsonian rats display measurable gait disturbances similar to PD patients that are not rescued by DA replacement. Furthermore, non-DA mechanisms such as attention-related NE in PFC may contribute to altered gait and may constitute a novel target for its treatment.

No Evidence of Sensory Neuropathy in a Traditional Mouse Model of Idiopathic Parkinson's Disease.

Parkinson's disease (PD) is the second-most common neurodegenerative disorder worldwide and is diagnosed based on motor impairments. Non-motor symptoms are also well-recognised in this disorder, and peripheral neuropathy is a frequent but poorly appreciated non-motor sign. Studying how central and peripheral sensory systems are affected can contribute to the development of targeted therapies and deepen our understanding of the pathophysiology of PD. Although the cause of sporadic PD is unknown, chronic exposure to the pesticide rotenone in humans increases the risk of developing the disease. Here, we aimed to investigate whether peripheral neuropathy is present in a traditional model of PD. Mice receiving intrastriatal rotenone showed greatly reduced dopamine terminals in the striatum and a reduction in tyrosine hydroxylase-positive neurons in the Substantia nigra pars compacta and developed progressive motor impairments in hindlimb stepping and rotarod but no change in spontaneous activity. Interestingly, repeated testing using gold-standard protocols showed no change in gut motility, a well-known non-motor symptom of PD. Importantly, we did not observe any change in heat, cold, or touch sensitivity, again based upon repeated testing with well-validated protocols that were statistically well powered. Therefore, this traditional model fails to replicate PD, and our data again reiterate the importance of the periphery to the disorder.

ATST-Net: A method to identify early symptoms in the upper and lower extremities of PD.

Bradykinesia, a core symptom of motor disorders in Parkinson's disease (PD), is a major criterion for screening early PD patients in clinical practice. Currently, many studies have proposed automatic assessment schemes for bradykinesia in PD. However, existing schemes suffer from problems such as dependence on professional equipment, single evaluation tasks, difficulty in obtaining samples and low accuracy. This paper proposes a manual feature extraction- and neural network-based method to evaluate bradykinesia, effectively solving the problem of a small sample size. This method can automatically assess finger tapping (FT), hand movement (HM), toe tapping (TT) and bilateral foot sensitivity tasks (LA) through a unified model. Data were obtained from 120 individuals, including 93 patients with Parkinson's disease and 27 age- and sex-matched normal controls (NCs). Manual feature extraction and Attention Time Series Two-stream Networks (ATST-Net) were used for classification. Accuracy rates of 0.844, 0.819, 0.728, and 0.768 were achieved for FT, HM, TT, and LA, respectively. To our knowledge, this study is the first to simultaneously evaluate the upper and lower limbs using a unified model that has significant advantages in both model training and transfer learning.

Effectiveness of vestibular rehabilitation on postural balance in Parkinson's disease: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Postural balance impairment can affect the quality of life of patients with Parkinson's disease. Previous studies have described connections of the vestibular system with postural functions, suggesting a potential participation of the basal ganglia in receiving vestibular stimuli. This systematic review aims to summarize the evidence on the effectiveness of vestibular rehabilitation on postural balance in patients with Parkinson's disease. METHODS: A systematic review was conducted using the electronic databases: PubMed, Embase, Scopus and PEDro. The study selection was independently conducted by two reviewers, and disagreements were evaluated by a third reviewer. The included studies had no restrictions on publication dates or languages and the last update occurred in July 2023. RESULTS: From the 485 studies found in the searches, only 3 studies were deemed eligible for the systematic review involving a total of 130 participants. The Berg Balance Scale was described as the tool for evaluation of postural balance in all studies. The meta-analysis showed statistically significant results in favor of vestibular rehabilitation (MD = 5.35; 95% CI = 2.39, 8.31; P < 0.001), regardless of the stage of Parkinson's disease. Although the effect size was suggested as a useful functional gain, the analysis was done with caution, as it only included 3 randomized controlled trials. The risk of bias using the RoB-2 was considered as being of "some concern" in all studies. Furthermore, the quality of the evidence based on the Grading of Recommendations Assessment Development and Evaluation system, produced by pooling the included studies was considered very low. CONCLUSION: Compared to other interventions, vestibular rehabilitation has potential to assist the postural balance of patients with Parkinson's disease. However, the very low quality of the evidence demonstrates uncertainty about the impact of this clinical practice. More robust studies are needed to confirm the benefits of this therapy in patients with Parkinson's disease. This study was prospectively registered in PROSPERO: CRD42020210185.