Motor Symptomatology Research Articles

Analysis of diffusion changes in cerebral tissues of Parki̇nson's patients who underwent subthalamic nucleus deep brain stimulation: Correlation of improvements in motor and neuropsychiatric symptoms

ObjectiveParkinson's disease (PD) as a neurodegenerative disorder characterized by a reduction in both the quantity and functionality of dopaminergic neurons. This succinctly highlights the central pathological feature of PD and its association with dopaminergic neuron degeneration, which underlies the motor and non-motor symptoms of the disease.This study aims to elucidate the nuances of apparent diffusion coefficient (ADC) changes in different cerebral regions by after the bilateral subthalamic nucleus (STN) deep brain stimulation (DBS) surgery of PD, as well as to investigate their potential interactions with the motor and neuropsychiatric spectrum. MethodsPatients who underwent STN-DBS surgery for PD between 2017 and 2019 were included in this study. The results of diffusion magnetic resonance imaging (MRI), Unified Parkinson Disease Rating Scale (UPDRS) III scores, Beck and Hamilton depression tests were recorded before and at the 3rd month of postoperative stimulation. The data obtained were evaluated with the Wilcoxon signed rank test. Result of the statistical tests were within the 95 % confidence interval and p values were significant below 0.05. ResultsOur study was conducted with a total of 13 patients, 8 men and 5 women. As a result of measurements made in a total of 32 different regions, especially in the motor and neuropsychiatric areas of the brain, an increase in ADC values was found in all areas. ADC changes of eight localizations such as left corpus callosum, right corona radiata, left corona radiata, hippocampus, right insula, left superior cerebellar peduncle, left caudate nucleus and left putamen were statistically significant. UPDRS III scores improved by 57 % (p <0.05), and Beck and Hamilton depression scores by 25 % and 33 %, respectively (p> 0.05). ConclusionsThis article implicate that bilateral STN-DBS surgery potentially exerts beneficial effects on both motor and neuropsychiatric symptomatology in individuals with PD. We believe that this therapeutic mechanism is hypothesized to involve modulation of diffusion alterations within distinct cerebral tissues.

Effects of Different Tonic, Isometric and Isometric/Vibratory Strength Training Programs on Motor Symptomatology in People with Parkinson’s Disease: Study Protocol for a Randomized Trial

Background: The Chilean population has experienced increased longevity in recent decades, leading to an increased incidence of and mortality from neurodegenerative diseases such as Parkinson’s disease (PD). PD is a chronic degenerative condition that affects the central nervous system. The main objective of this research is to evaluate the effect of 12-week programs of tonic, isometric, and isometric/vibratory muscular strength training while controlling the manipulation of the intensity variable on motor and non-motor symptomatology in PD patients. The secondary objective is to assess the levels of muscular strength in PD patients and their relationship with motor and non-motor symptomatology. Methods: A parallel-group, randomized trial will randomly assign (n = 34) people of both sexes with Parkinson’s disease between stages I–III Hoehn and Yahr (H&amp;Y), aged between 50 and 70 years to one of the experimental groups, in which they will undergo a total of 24 strength training sessions during 12 weeks. During the intervention period, the participants will be advised not to undertake additional exercise programs, to avoid substances that may disrupt metabolism and circadian cycles, and to maintain their medication regimen. The primary or motor evaluation of rest tremor will be performed with an accelerometer (Actigraphy), balance with the Mini-BESTest balance test, gait speed with the Ten Meters Walk Test, and non-motor symptomatology through anxiety, depression (MDS-UPDRS), and quality of life (PDQ-39) questionnaires. The Secondary evaluation of muscle strength will be performed with a functional electromechanical dynamometer. Discussion: Established as a hypothesis is that manipulating intensity variables in 12-week tonic, isometric, and isometric/vibratory muscle strength training programs has an effect on motor and non-motor symptomatology in people with Parkinson’s disease. The research will establish the extent to which controlled muscular strength training has an effect on relevant factors related to motor and non-motor symptomatology.

Single nuclei RNA-seq reveals a medium spiny neuron glutamate excitotoxicity signature prior to the onset of neuronal death in an ovine Huntington's disease model.

Huntington's disease (HD) is a neurodegenerative genetic disorder caused by an expansion in the CAG repeat tract of the huntingtin (HTT) gene resulting in behavioural, cognitive, and motor defects. Current knowledge of disease pathogenesis remains incomplete, and no disease course-modifying interventions are in clinical use. We have previously reported the development and characterisation of the OVT73 transgenic sheep model of HD. The 73 polyglutamine repeat is somatically stable and therefore likely captures a prodromal phase of the disease with an absence of motor symptomatology even at 5-years of age and no detectable striatal cell loss. To better understand the disease-initiating events we have undertaken a single nuclei transcriptome study of the striatum of an extensively studied cohort of 5-year-old OVT73 HD sheep and age matched wild-type controls. We have identified transcriptional upregulation of genes encoding N-methyl-D-aspartate (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors in medium spiny neurons, the cell type preferentially lost early in HD. Further, we observed an upregulation of astrocytic glutamate uptake transporters and medium spiny neuron GABAA receptors, which may maintain glutamate homeostasis. Taken together, these observations support the glutamate excitotoxicity hypothesis as an early neurodegeneration cascade-initiating process but the threshold of toxicity may be regulated by several protective mechanisms. Addressing this biochemical defect early may prevent neuronal loss and avoid the more complex secondary consequences precipitated by cell death.

Lifestyle Modulators of Neuroplasticity in Parkinson's Disease: Evidence in Human Neuroimaging Studies.

Parkinson's disease (PD) is a neurodegenerative disease characterized by both motor and non-motor symptoms. A progressive neuronal loss and the consequent clinical impairment lead to deleterious effects on daily living and quality of life. Despite effective symptomatic therapeutic approaches, no disease-modifying therapies are currently available. Emerging evidence suggests that adopting a healthy lifestyle can improve the quality of life of PD patients. In addition, modulating lifestyle factors can positively affect the microstructural and macrostructural brain levels, corresponding to clinical improvement. Neuroimaging studies may help to identify the mechanisms through which physical exercise, dietary changes, cognitive enrichment, and exposure to substances modulate neuroprotection. All these factors have been associated with a modified risk of developing PD, with attenuation or exacerbation of motor and non-motor symptomatology, and possibly with structural and molecular changes. In the present work, we review the current knowledge on how lifestyle factors influence PD development and progression and the neuroimaging evidence for the brain structural, functional, and molecular changes induced by the adoption of positive or negative lifestyle behaviours.

Electrophysiological signatures of anxiety in Parkinson’s disease

Anxiety is a common non-motor symptom in Parkinson’s disease (PD) occurring in up to 31% of the patients and affecting their quality of life. Despite the high prevalence, anxiety symptoms in PD are often underdiagnosed and, therefore, undertreated. To date, functional and structural neuroimaging studies have contributed to our understanding of the motor and cognitive symptomatology of PD. Yet, the underlying pathophysiology of anxiety symptoms in PD remains largely unknown and studies on their neural correlates are missing. Here, we used resting-state electroencephalography (RS-EEG) of 68 non-demented PD patients with or without clinically-defined anxiety and 25 healthy controls (HC) to assess spectral and functional connectivity fingerprints characterizing the PD-related anxiety. When comparing the brain activity of the PD anxious group (PD-A, N = 18) to both PD non-anxious (PD-NA, N = 50) and HC groups (N = 25) at baseline, our results showed increased fronto-parietal delta power and decreased frontal beta power depicting the PD-A group. Results also revealed hyper-connectivity networks predominating in delta, theta and gamma bands against prominent hypo-connectivity networks in alpha and beta bands as network signatures of anxiety in PD where the frontal, temporal, limbic and insular lobes exhibited the majority of significant connections. Moreover, the revealed EEG-based electrophysiological signatures were strongly associated with the clinical scores of anxiety and followed their progression trend over the course of the disease. We believe that the identification of the electrophysiological correlates of anxiety in PD using EEG is conducive toward more accurate prognosis and can ultimately support personalized psychiatric follow-up and the development of new therapeutic strategies.

Microglial and Astrocytic Responses in the Human Midcingulate Cortex in Huntington's Disease.

Patients with Huntington's disease can present with variable difficulties of motor functioning, mood, and cognition. Neurodegeneration occurs in the anterior cingulate cortex of some patients with Huntington's disease and is linked to the presentation of mood symptomatology. Neuroinflammation, perpetrated by activated microglia and astrocytes, has been reported in Huntington's disease and may contribute to disease progression and presentation. This study sought to quantify the density of mutant huntingtin protein and neuroinflammatory glial changes in the midcingulate cortex of postmortem patients with Huntington's disease and determine if either correlates with the presentation of mood, motor, or mixed symptomatology. Free-floating immunohistochemistry quantified 1C2 immunolabeling density as an indicative marker of mutant huntingtin protein, and protein and morphological markers of astrocyte (EAAT2, Cx43, and GFAP), and microglial (Iba1 and HLA-DP/DQ/DR) activation. Relationships among the level of microglial activation, mutant huntingtin burden, and case characteristics were explored using correlative analysis. We report alterations in activated microglia number and morphology in the midcingulate cortex of Huntington's disease cases with predominant mood symptomatology. An increased proportion of activated microglia was observed in the midcingulate of all Huntington's disease cases and positively correlated with 1C2 burden. Alterations in the astrocytic glutamate transporter EAAT2 were observed in the midcingulate cortex of patients associated with mood symptoms. This study presents pathological changes in microglia and astrocytes in the midcingulate cortex in Huntington's disease, which coincide with mood symptom presentation. These findings further the understanding of neuroinflammation in Huntington's disease, a necessary step for developing inflammation-targeted therapeutics. ANN NEUROL 2023;94:895-910.

Tumoral parkinsonism-Parkinsonism secondary to brain tumors, paraneoplastic syndromes, intracranial malformations, or oncological intervention, and the effect of dopaminergic treatment.

Secondary tumoral parkinsonism is a rare phenomenon that develops as a direct or indirect result of brain neoplasms or related conditions. The first objective was to explore to what extent brain neoplasms, cavernomas, cysts, paraneoplastic syndromes (PNSs), and oncological treatment methods cause parkinsonism. The second objective was to investigate the effect of dopaminergic therapy on the symptomatology in patients with tumoral parkinsonism. A systematic literature review was conducted in the databases PubMed and Embase. Search terms like "secondary parkinsonism," "astrocytoma," and "cranial irradiation" were used. Articles fulfilling inclusion criteria were included in the review. Out of 316 identified articles from the defined database search strategies, 56 were included in the detailed review. The studies, which were mostly case reports, provided research concerning tumoral parkinsonism and related conditions. It was found that various types of primary brain tumors, such as astrocytoma and meningioma, and more seldom brain metastases, can cause tumoral parkinsonism. Parkinsonism secondary to PNSs, cavernomas, cysts, as well as oncological treatments was reported. Twenty-five of the 56 included studies had tried initiating dopaminergic therapy, and of these 44% reported no, 48% low to moderate, and 8% excellent effect on motor symptomatology. Brain neoplasms, PNSs, certain intracranial malformations, and oncological treatments can cause parkinsonism. Dopaminergic therapy has relatively benign side effects and may relieve motor and nonmotor symptomatology in patients with tumoral parkinsonism. Dopaminergic therapy, particularly levodopa, should therefore be considered in patients with tumoral parkinsonism.

N-Acetylcysteine Treatment May Compensate Motor Impairments through Dopaminergic Transmission Modulation in a Striatal 6-Hydroxydopamine Parkinson's Disease Rat Model.

Preventing degeneration and the loss of dopaminergic neurons (DAn) in the brain while mitigating motor symptoms remains a challenge in Parkinson's Disease (PD) treatment development. In light of this, developing or repositioning potential disease-modifying approaches is imperative to achieve meaningful translational gains in PD research. Under this concept, N-acetylcysteine (NAC) has revealed promising perspectives in preserving the dopaminergic system capability and modulating PD mechanisms. Although NAC has been shown to act as an antioxidant and (neuro)protector of the brain, it has yet to be acknowledged how this repurposed drug can improve motor symptomatology and provide disease-modifying properties in PD. Therefore, in the present work, we assessed the impact of NAC on motor and histological deficits in a striatal 6-hydroxydopamine (6-OHDA) rat model of PD. The results revealed that NAC enhanced DAn viability, as we found that it could restore dopamine transporter (DAT) levels compared to the untreated 6-OHDA group. Such findings were positively correlated with a significant amelioration in the motor outcomes of the 6-OHDA-treated animals, demonstrating that NAC may, somehow, be a modulator of PD degenerative mechanisms. Overall, we postulated a proof-of-concept milestone concerning the therapeutic application of NAC. Nevertheless, it is extremely important to understand the complexity of this drug and how its therapeutical properties interact with the cellular and molecular PD mechanisms.

Electrophysiological Signatures of Anxiety in Parkinson’s Disease (S51.008)

<h3>Objective:</h3> To assess the pattern of disturbances in the functional brain networks of Parkinson’s disease patients with anxiety (PD-A) compared to those without anxiety (PD-NA) and healthy controls (HC). <h3>Background:</h3> Anxiety is a common non motor symptom in PD occurring in up to 60% of the patients and affecting their quality of life. Despite their high prevalence, anxiety symptoms are often undiagnosed and untreated in PD. To date, functional and structural neuroimaging studies have contributed to our understanding of the motor and cognitive symptomatology of PD. Yet, the underlying pathophysiology of the anxiety symptoms in PD remains largely unknown and studies on their neural correlates are missing. <h3>Design/Methods:</h3> The present study comprised 68 non-demented PD patients and 25 healthy controls. PD patients were divided into two subgroups based on their Beck Anxiety Inventory (BAI) scale (cut-off=13): PD patients with anxiety (N=18) and without anxiety (N=50). Using their resting state high density electroencephalography (EEG) recordings at baseline, we assessed the frequency-dependent functional connectivity patterns that characterize the PD-A patients compared to both PD-NA patients and HC and we validated their relevance after 3 years. <h3>Results:</h3> We revealed different frequency-dependent pattern of connectivity that can characterize the PD-A group compared to PD-NA and HC: patterns with high functional connectivity were observed in delta, theta and gamma bands involving mainly fronto-temporal connections, whereas fronto-parietal patterns with low functional connectivity were pertinent in alpha and beta bands. Their corresponding network signature metric were strongly correlated with the anxiety scale of all the participants at baseline and after 3 years showing a predictive power of the revealed networks. <h3>Conclusions:</h3> Our findings suggest that PD-related anxiety can be characterized by a signature of different frequency-dependent pattern of disturbances in the functional brain networks. Resting state EEG could be a very promising biomarker for early detection of anxiety in PD. <b>Disclosure:</b> Mrs. Yassine has nothing to disclose. Mrs. Almarouk has nothing to disclose. Ute Gschwandtner has nothing to disclose. Dr. Auffret has received personal compensation for serving as an employee of France Développement Electronique. The institution of Dr. Auffret has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Britannia. Dr. Auffret has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Britannia. Dr. Auffret has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Britannia. Dr. Auffret has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Aguettant. The institution of Dr. Auffret has received research support from Association France Parkinson. The institution of Dr. Auffret has received research support from Homeperf. The institution of Dr. Auffret has received research support from LVL. The institution of Dr. Auffret has received research support from University of Rennes 1. The institution of Dr. Auffret has received research support from Aguettant. The institution of Dr. Auffret has received research support from Linde. The institution of Dr. Auffret has received research support from Plateforme Nationale pour la recherche sur la fin de vie. Dr. Auffret has received publishing royalties from a publication relating to health care. Mr. HASSAN has nothing to disclose. The institution of Dr. Fuhr has received research support from Roche. Mr. Verin has nothing to disclose.

Chorea Severity Change Over Time in Huntington Disease and by Huntington Disease Stage (P1-11.010)

<h3>Objective:</h3> To describe chorea severity over time in individuals with Huntington disease (HD) stratified by Total Functional Capacity (TFC). <h3>Background:</h3> Chorea, the most common motor symptom in HD, negatively affects quality of life and TFC. Addressing chorea is crucial to reduce the burden of motor symptomatology in HD. Chorea has been reported to increase initially, plateau, and potentially decrease over time; however, longitudinal data assessing chorea severity by disease stage are limited. <h3>Design/Methods:</h3> Participants were adults from Enroll-HD, a global, longitudinal, observational registry for individuals with or at risk for HD (data cut 2013–31 October 2020). The manifest population was stratified by baseline TFC score as a proxy for HD stage (TFC 7–13/stage 1–2 [early], 3–6/stage 3 [middle], 0–2/stage 4–5 [late]). Chorea severity was assessed by Total Maximal Chorea (TMC) score at baseline and at annual visits. Patients with ≥4 years of follow-up were selected for estimating chorea progression over time. <h3>Results:</h3> The manifest population was grouped by HD stage: early, n=7441; middle, n=2330; late, n=1120. Baseline TMC scores (mean [SD]) increased as HD stage progressed (early, 8.0 [4.7]; middle, 10.4 [5.8]; late, 10.6 [6.9]). For participants with ≥4 years of follow-up (n=1271), TMC scores increased over time in early-stage HD (n=963; years 1–2, 8.5 [5.0]; years 2–3, 9.1 [5.3]; years 3–4, 9.5 [5.6]), but plateaued at high levels in middle- (n=222; 10.6 [5.3]; 10.6 [6.0]; 10.1 [5.7], respectively) and late-stage HD (n=86; 10.4 [6.6]; 9.8 [6.9]; 9.7 [6.2]). <h3>Conclusions:</h3> Chorea severity increased in early-stage HD, and plateaued in middle- and late-stage HD. Chorea severity did not decrease longitudinally in any stage; however, the limited sample size for the follow-up period should be considered. These results support the need for increased awareness about the potential for persistent chorea in late-stage HD. <b>Disclosure:</b> Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Teva Pharmaceuticals. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Michael J. Fox Foundation. Dr. Furr-Stimming has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Teva Pharmaceuticals. The institution of Dr. Furr-Stimming has received research support from Cures within Reach. The institution of Dr. Furr-Stimming has received research support from Huntington’s Disease Society of America. The institution of Dr. Furr-Stimming has received research support from Roche/Genetech. The institution of Dr. Furr-Stimming has received research support from Uniqure. The institution of Dr. Furr-Stimming has received research support from CHDI. The institution of Dr. Furr-Stimming has received research support from Huntington Study Group/Neurocrine. The institution of Dr. Furr-Stimming has received research support from NIH/University of Iowa. The institution of Dr. Furr-Stimming has received research support from Sage Therapeutics. Dr. Furr-Stimming has received publishing royalties from a publication relating to health care. Dr. Sung has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva Neuroscience. Dr. Sung has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Reshef has received personal compensation for serving as an employee of Teva. Ms. Willock has received personal compensation for serving as an employee of HCD Economics. Rinat Ribalov has received personal compensation for serving as an employee of TEVA. Miss Brighton has nothing to disclose. Dr. Leo has received personal compensation for serving as an employee of Teva Pharmaceutical Industries.

The Phase 2, Randomized, Placebo-controlled PRECEDENT Trial of SAGE-718 in Patients With Parkinson's Disease Cognitive Impairment: Clinical Trial in Progress (P2-11.005)

<h3>Objective:</h3> The randomized, placebo-controlled PRECEDENT Study is designed to evaluate the efficacy, safety, and tolerability of SAGE-718 as a potential treatment for cognitive impairment due to Parkinson’s disease (PD). <h3>Background:</h3> PD is a multisystem disorder with diverse clinical features, including neuropsychiatric symptoms and non-motor manifestations alongside motor symptomatology. Cognitive impairment, a common non-motor symptom of PD, contributes to poor functional outcomes, loss of independence, and increased risk of dementia. A significant unmet need exists for effective and well-tolerated pharmacotherapies that address cognitive impairment due to PD. Positive modulation of NMDA receptors may improve cognitive deficits. SAGE-718, an investigational NMDA receptor positive allosteric modulator, has been associated with improved cognitive performance in patients with PD and other neurodegenerative diseases. <h3>Design/Methods:</h3> PRECEDENT (NCT05318937) is a Phase 2, randomized, double-blind, placebo-controlled trial that includes a 3-week screening period, a 1-week baseline period, a 6-week treatment period, and a 4-week follow-up period. Approximately 76 patients aged 50–75 years meeting Movement Disorder Society Task Force Criteria for PD Mild Cognitive Impairment with mild-to-moderate motor involvement will be randomized 1:1 to receive either SAGE-718 or placebo once daily for 42 days. The primary endpoint is change from baseline in the Wechsler Adult Intelligence Scale-IV Coding score (a measure of executive functioning) at Day 42. Secondary endpoints include the proportion of patients with treatment-emergent adverse events (TEAEs), severity of TEAEs, and number of patients who withdraw from the study due to TEAEs. Other endpoints include additional assessments of cognitive performance, safety/tolerability, motor symptoms, functioning, and pharmacokinetics. <h3>Results:</h3> PRECEDENT is currently enrolling at sites in the United States. <h3>Conclusions:</h3> PRECEDENT is designed to evaluate the efficacy, safety, and tolerability of SAGE-718 in patients with cognitive impairment due to PD. <b>Disclosure:</b> Dr. Bullock has received personal compensation for serving as an employee of Sage Therapeutics, Inc. . Dr. Bullock has stock in Sage Therapeutics, Inc. Aaron Koenig has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Paumier has nothing to disclose. Ms. Freitag has nothing to disclose. Jeffrey Wald has received personal compensation for serving as an employee of Sage Therapeutics. Jeffrey Wald has received stock or an ownership interest from Sage Thereapeutics. Dr. Park has nothing to disclose. Michael Quirk has received personal compensation for serving as an employee of Sage Therapeutics. Michael Quirk has received stock or an ownership interest from Sage Therapeutics. Jennifer Petrillo, 14951 has received personal compensation for serving as an employee of Sage Therapeutics. Jennifer Petrillo, 14951 has received stock or an ownership interest from Sage Therapeutics. Dr. Doherty has received personal compensation for serving as an employee of Sage Therapeutics. Dr. Doherty has received stock or an ownership interest from Sage Therapeutics.

Hypermanganesemia with Dystonia Type 2: A Rare Entity. (P12-11.001)

<h3>Objective:</h3> NA <h3>Background:</h3> Hypermanganesemia with dystonia type 2 is an established, rare autosomal recessive partially reversible neurodegenerative condition characterised by mutations in the SLC39A14 gene. Manganese deposition in such cases has a special predilection for the basal ganglia structures leading to dystonia and parkinsonian features. We report such a case of hypermanganesemia in a 1 year old child presenting with extrapyramidal features. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 1 year old female child presented with regression of developmental milestones for the past 2 months, losing the ability to stand or even sit without support—skills that she had previously acquired at an appropriate time. This was associated with dystonic posturing of her neck and limbs for the last 1 month. Cognitive skills were normal as per her age without any history of convulsions or other systemic features. Her birth and family history were unremarkable. Her neurological examination was remarkable only for generalised dystonia of her limbs, neck and trunk. Magnetic resonance imaging was suggestive of paramagnetic substance deposition in bilateral basal ganglia and dentate nucleus. Normal routine blood parameters were followed by extensive investigations to rule out Wilson’s disease, NBIA and other autoimmune pathologies. Her blood manganese levels were significantly elevated and her genetic sequencing revealed compound heterozygous mutations of the SLC39A14 gene at exons 7 and 8. She was started on chelation therapy with Penicillamine and oral iron. Dystonia resolved significantly by the end of 6 months of therapy with marked improvement in her motor developmental milestones. <h3>Conclusions:</h3> Hypermanganesemia with dystonia type 2 (HMNDYT2) is a rare genetic disorder characterised by neuronal manganese deposition without other systemic features. This case highlights the importance of recognising this potentially rare treatable condition and with adequate chelation therapy at the right time, near total restoration of motor symptomatology is possible. <b>Disclosure:</b> Dr. Bhattacharya has nothing to disclose. Dr. Chintha has nothing to disclose. Dr. Biswas has nothing to disclose. Dr. Das has nothing to disclose. Dr. Chakraborty has nothing to disclose. Dr. Mukherjee has nothing to disclose.

Attentional impairment in Parkinson’s disease is modulated by side of onset: Neurophysiological evidence

ObjectiveNeurophysiological studies exploring involuntary attention have reported that electroencephalographic (EEG) measures can indicate impaired neural processing from initial stages of Parkinson’s disease (PD). Since involuntary attention is regulated by right hemisphere networks and PD generally initiates its motor symptomatology unilaterally, whether involuntary attention is impaired depending on the onset side of PD remains unknown. MethodsWe compared the neurophysiological correlates of involuntary attention among a PD group with left-side onset (L-PD), a PD group with right-side onset (R-PD) symptomatology, and a healthy control group (HC). All participants performed an auditory involuntary attention task while a digital EEG was recorded. ResultsOur main finding was a reduction both in the P3a amplitude and evoked delta-theta phase alignment in the L-PD group compared to the HC. Further, there was a significant correlation between P3a amplitude and disease duration in the R-PD, but not in the L-PD group. Behaviorally, both clinical groups, and in particular L-PD, showed reduced orientation towards novel stimuli, and no reduction of distraction effects during the experiment. ConclusionsOur results indicate that involuntary attention is differentially impaired in patients with left side onset of symptoms. Involuntary attention impairment might be present from initial stages of left onset PD and become progressively compromised in patients with right onset PD. SignificanceThe onset side of symptomatology should be considered for attentional impairment in PD.

TU-204. Attentional impairment in Parkinson’s disease is modulated by the side of motor symptomatology onset: Neurophysiological and behavioral evidence

TU-204. Attentional impairment in Parkinson’s disease is modulated by the side of motor symptomatology onset: Neurophysiological and behavioral evidence

Neuropsychiatric Symptoms in Clinically Defined Parkinson's Disease: An Updated Review of Literature.

Background Neuropsychiatric symptoms (NPS) are a common and potentially serious manifestation of Parkinson's disease (PD) but are frequently overlooked in favor of a focus on motor symptomatology. Here, we conducted a literature review of the prevalence and type of NPS experienced by PD patients with a clinically defined course of their illness. Methods We identified reports of NPS in patients with PD and mean disease duration over 3 years. Three databases—PubMed, Scopus, and Dialnet—were searched for relevant literature published between 2010 and 2020. Predefined exclusion criteria were applied prior to a descriptive analysis of the literature base. Results In all, 87 unique reports were identified and 30 met inclusion and exclusion criteria. These included 7142 patients with PD (male: 67.3%; mean age: 66.2 years; mean disease duration: 6.7 years). The most frequent NPS were mood disorders (apathy, depression, and anxiety), psychosis, and impulse control disorders (ICD). Treatment with dopamine agonists was identified as an important risk factor for ICD. Co-occurrence of NPS and cognitive dysfunction was also evidenced in a number of studies. Patients with more significant cognitive deficits and higher levels of NPS appeared to be of older age with a longer disease duration and to have more severe motor symptoms. Conclusions NPS, most commonly mood disorders (apathy, depression, and anxiety), psychosis, and ICDs are frequent manifestations of PD. The results of this review reflect the need to develop unified validated assessment protocols for NPS in PD, as well as to improve their management in clinical practice.

Benefits of Tango Therapy in Alleviating the Motor and Non-Motor Symptoms of Parkinson's Disease Patients-A Narrative Review.

The present study examines the efficacy of tango therapy on motor and non-motor symptomatology in Parkinson’s disease, as detailed in articles published over the previous four decades (1980–2022). All data was collected using PubMed, Google Scholar, Web of Science, and Science Direct. The present descriptive study outlines the advantages of tango in the rehabilitation of Parkinson’s disease’s motor and non-motor symptoms. Numerous studies have been conducted to determine the usefulness of tango for people with PD. Information from various research is critical for determining if tango is a useful supplementary therapy for the variety of symptoms related to Parkinson’s disease. The purpose of this review was to describe the present state of research on this subject. Thus, the objective of this review is to promote awareness of tango therapy’s therapeutic benefits for Parkinson’s disease.

Cascaded Deep Learning Frameworks in Contribution to the Detection of Parkinson's Disease.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor impairment, as well as tremors, stiffness, and rigidity. Besides the typical motor symptomatology, some Parkinsonians experience non-motor symptoms such as hyposmia, constipation, urinary dysfunction, orthostatic hypotension, memory loss, depression, pain, and sleep disturbances. The correct diagnosis of PD cannot be easy since there is no standard objective approach to it. After the incorporation of machine learning (ML) algorithms in medical diagnoses, the accuracy of disease predictions has improved. In this work, we have used three deep-learning-type cascaded neural network models based on the audial voice features of PD patients, called Recurrent Neural Networks (RNN), Multilayer Perception (MLP), and Long Short-Term Memory (LSTM), to estimate the accuracy of PD diagnosis. A performance comparison between the three models was performed on a sample of the subjects’ voice biomarkers. Experimental outcomes suggested that the LSTM model outperforms others with 99% accuracy. This study has also presented loss function curves on the relevance of good-fitting models to the detection of neurodegenerative diseases such as PD.

Sex Differences in Brain and Cognition in de novo Parkinson's Disease.

Background and Objective: Brain atrophy and cognitive impairment in neurodegenerative diseases are influenced by sex. We aimed to investigate sex differences in brain atrophy and cognition in de novo Parkinson's disease (PD) patients.Methods: Clinical, neuropsychological and T1-weighted MRI data from 205 PD patients (127 males: 78 females) and 69 healthy controls (40 males: 29 females) were obtained from the PPMI dataset.Results: PD males had a greater motor and rapid eye movement sleep behavior disorder symptomatology than PD females. They also showed cortical thinning in postcentral and precentral regions, greater global cortical and subcortical atrophy and smaller volumes in thalamus, caudate, putamen, pallidum, hippocampus, and brainstem, compared with PD females. Healthy controls only showed reduced hippocampal volume in males compared to females. PD males performed worse than PD females in global cognition, immediate verbal recall, and mental processing speed. In both groups males performed worse than females in semantic verbal fluency and delayed verbal recall; as well as females performed worse than males in visuospatial function.Conclusions: Sex effect in brain and cognition is already evident in de novo PD not explained by age per se, being a relevant factor to consider in clinical and translational research in PD.

Therapeutic Exercise and Conservative Injection Treatment for Early Knee Osteoarthritis in Athletes: A Scoping Review.

Background and Objectives: Recent evidence highlighted a higher prevalence of knee osteoarthritis (kOA) among young and former ex-professional athletes. Although the practice of a highly demanding sport is considered a predisposing factor for the knee joint cartilage degeneration, articular cartilage seems to positively respond to a moderate load increase. We aim to investigate recent evidence on the conservative management of early kOA in athletes, with a particular emphasis on therapeutic exercise and injection treatment, in order to highlight whether there are any indications that can influence clinical and rehabilitation practice. Materials and Methods: A scoping review was conducted, screening MEDLINE and PEDro databases for studies published over the past twenty years on the topic. Studies in English, with accessible abstracts, were included in the review. The PICO framework was used (P—patient: athletes, I—Intervention: conservative treatment with therapeutic exercise or injection therapies, C—Comparison: not needed, O—Outcomes: clinical outcomes). Clinical trials, randomized controlled trials, and longitudinal studies were considered. Results: Four studies were finally included in the review. Therapeutic exercise seems to have beneficial effects on prevention of cartilage degeneration, on pain reduction, and on physical function enhancement. On the other hand, in mild to moderate stages of kOA the intra-articular viscosupplementation with Hyaluronic Acid showed a medium to long-term improvement in joint pain and function. The Platelet Rich Plasma treatment also showed a significant improvement in pain and function up to 12 months. Conclusions: Despite the heterogeneity of the studies considered, a multimodal treatment combining therapeutic exercise and moderate aerobic activity (such as running) should be indicated to prevent kOA development. In cases of symptomatic kOA it may be indicated to add minimally invasive injection therapy that seems to contribute to the improvement of motor function and symptomatology.

A Different Kind of Hemiplegic Migraine Gene

The key clinical feature of hemiplegic migraine (HM) is motor aura symptomatology. The diagnosis is confirmed by the finding of autosomal dominantly